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Xu H, Lin S, Hua Y. Innovations in aggregation-induced emission materials for theranostics in the musculoskeletal system. Biosens Bioelectron 2025; 271:117069. [PMID: 39721462 DOI: 10.1016/j.bios.2024.117069] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Revised: 12/07/2024] [Accepted: 12/13/2024] [Indexed: 12/28/2024]
Abstract
Aggregation-induced emission (AIE) offers a promising solution for achieving lower background and more reliable signals in biomedical imaging. AIE materials also exhibiting photostability and resistance to photobleaching. These characters are crucial for monitoring musculoskeletal functions and offering targeted therapies for related diseases. This review compiles research on AIEgens targeting various molecules, cells, or tissues within the musculoskeletal system under physiological or pathological conditions and classifies them according to different clinical applications. A sort of AIEgens is applied in monitoring osteogenic differentiation and bone component analysis. Additionally, AIEgens targeting intra-articular inflammatory or rheumatic related molecules, such as reactive oxygen species, enable early-stage diagnosis and targeted therapies of arthritis. Researchers have also developed novel materials containing AIEgens for joint tissue repair. This review highlights the advantages of these applications while also exploring future demands and development directions in musculoskeletal system imaging and treatment, aiming to promote further design of AIEgens and their clinical applications in musculoskeletal diseases.
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Affiliation(s)
- Hanlin Xu
- Department of Sports Medicine, Huashan Hospital, Fudan University, No.12 Urumqi Middle Rd., Shanghai, 200040, China
| | - Shangqian Lin
- Department of Clinical Medicine, Shanghai Medical College, Fudan University, No.138 Yixueyuan Rd., Shanghai, 200032, China
| | - YingHui Hua
- Department of Sports Medicine, Huashan Hospital, Fudan University, No.12 Urumqi Middle Rd., Shanghai, 200040, China.
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Moghtaderi H, Mohahammadi S, Sadeghian G, Choudhury M, Al-Harrasi A, Rahman SM. Electrical impedance sensing in stem cell research: Insights, applications, and future directions. PROGRESS IN BIOPHYSICS AND MOLECULAR BIOLOGY 2025; 195:1-14. [PMID: 39557164 DOI: 10.1016/j.pbiomolbio.2024.11.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Revised: 11/14/2024] [Accepted: 11/15/2024] [Indexed: 11/20/2024]
Abstract
The exceptional differentiation abilities of stem cells make them ideal candidates for cell replacement therapies. Considering their great potential, researchers should understand how stem cells interact with other cell types. The production of high-quality differentiated cells is crucial for favorable treatment and makes them an ideal choice for clinical applications. Label-free stem cell monitoring approaches are anticipated to be more effective in this context, as they ensure quality of differentiation while preserving the therapeutic potential. Electric cell-substrate impedance sensing (ECIS) is a nonintrusive technique that enables cell quantification through continuous monitoring of adherent cell behavior using electronic transcellular impedance measurements. This technique also facilitates the study of cell growth, motility, differentiation, drug effects, and cell barrier functions. Therefore, numerous studies have identified ECIS as an effective method for monitoring stem cell quality and differentiation. In this review, we discuss the current understanding of ECIS's achievements in examining cell behaviors and the potential applications of ECIS arrays in preclinical stem cell research. Moreover, we highlight our present knowledge concerning ECIS's contributions in examining cell behaviors and speculate about the future uses of ECIS arrays in preclinical stem cell research. This review also aims to stimulate research on electrochemical biosensors for future applications in regenerative medicine.
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Affiliation(s)
- Hassan Moghtaderi
- Natural and Medical Sciences Research Center, University of Nizwa, Nizwa, 616, Sultanate of Oman
| | - Saeed Mohahammadi
- Natural and Medical Sciences Research Center, University of Nizwa, Nizwa, 616, Sultanate of Oman
| | - Golfam Sadeghian
- Advanced Micro and Nano Device Laboratory, Faculty of New Sciences and Technologies, University of Tehran, Tehran, 1439957131, Iran
| | - Mahua Choudhury
- Department of Pharmaceutical Sciences, School of Pharmacy, Texas A & M University, College Station, TX, 77843, USA
| | - Ahmed Al-Harrasi
- Natural and Medical Sciences Research Center, University of Nizwa, Nizwa, 616, Sultanate of Oman
| | - Shaikh Mizanoor Rahman
- Natural and Medical Sciences Research Center, University of Nizwa, Nizwa, 616, Sultanate of Oman.
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3
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Oliveira BA, Levy D, Paz JL, de Freitas FA, Reichert CO, Rodrigues A, Bydlowski SP. 7-Ketocholesterol Effects on Osteogenic Differentiation of Adipose Tissue-Derived Mesenchymal Stem Cells. Int J Mol Sci 2024; 25:11380. [PMID: 39518932 PMCID: PMC11545361 DOI: 10.3390/ijms252111380] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Revised: 10/15/2024] [Accepted: 10/21/2024] [Indexed: 11/16/2024] Open
Abstract
Some oxysterols were shown to promote osteogenic differentiation of mesenchymal stem cells (MSCs). Little is known about the effects of 7-ketocholesterol (7-KC) in this process. We describe its impact on human adipose tissue-derived MSC (ATMSC) osteogenic differentiation. ATMSCs were incubated with 7-KC in osteogenic or adipogenic media. Osteogenic and adipogenic differentiation was evaluated by Alizarin red and Oil Red O staining, respectively. Osteogenic (ALPL, RUNX2, BGLAP) and adipogenic markers (PPARƔ, C/EBPα) were determined by RT-PCR. Differentiation signaling pathways (SHh, Smo, Gli-3, β-catenin) were determined by indirect immunofluorescence. ATMSCs treated with 7-KC in osteogenic media stained positively for Alizarin Red. 7-KC in adipogenic media decreased the number of adipocytes. 7-KC increased ALPL and RUNX2 but not BGLAP expressions. 7-KC decreased expression of PPARƔ and C/EBPα, did not change SHh, Smo, and Gli-3 expression, and increased the expression of β-catenin. In conclusion, 7-KC favors osteogenic differentiation of ATMSCs through the expression of early osteogenic genes (matrix maturation phase) by activating the Wnt/β-catenin signaling pathway, while inhibiting adipogenic differentiation. This knowledge can be potentially useful in regenerative medicine, in treatments for bone diseases.
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Affiliation(s)
- Beatriz Araújo Oliveira
- Lipids, Oxidation, and Cell Biology Team, Laboratory of Immunology (LIM19), Heart Institute (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-900, SP, Brazil (D.L.); (F.A.d.F.); (C.O.R.)
| | - Débora Levy
- Lipids, Oxidation, and Cell Biology Team, Laboratory of Immunology (LIM19), Heart Institute (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-900, SP, Brazil (D.L.); (F.A.d.F.); (C.O.R.)
| | - Jessica Liliane Paz
- Lipids, Oxidation, and Cell Biology Team, Laboratory of Immunology (LIM19), Heart Institute (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-900, SP, Brazil (D.L.); (F.A.d.F.); (C.O.R.)
| | - Fabio Alessandro de Freitas
- Lipids, Oxidation, and Cell Biology Team, Laboratory of Immunology (LIM19), Heart Institute (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-900, SP, Brazil (D.L.); (F.A.d.F.); (C.O.R.)
| | - Cadiele Oliana Reichert
- Lipids, Oxidation, and Cell Biology Team, Laboratory of Immunology (LIM19), Heart Institute (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-900, SP, Brazil (D.L.); (F.A.d.F.); (C.O.R.)
| | - Alessandro Rodrigues
- Department of Earth and Exact Sciences, Universidade Federal de Sao Paulo, Diadema 09972-270, SP, Brazil;
| | - Sérgio Paulo Bydlowski
- Lipids, Oxidation, and Cell Biology Team, Laboratory of Immunology (LIM19), Heart Institute (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-900, SP, Brazil (D.L.); (F.A.d.F.); (C.O.R.)
- National Institute of Science and Technology for Regenerative Medicine (INCT Regenera), National Council for Scientific and Technological Development (CNPq), Rio de Janeiro 21941-902, RJ, Brazil
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Wang Y, Hang K, Wu X, Ying L, Wang Z, Ling Z, Hu H, Pan Z, Zou X. SLAMF8 regulates osteogenesis and adipogenesis of bone marrow mesenchymal stem cells via S100A6/Wnt/β-catenin signaling pathway. Stem Cell Res Ther 2024; 15:349. [PMID: 39380096 PMCID: PMC11462740 DOI: 10.1186/s13287-024-03964-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Accepted: 09/29/2024] [Indexed: 10/10/2024] Open
Abstract
BACKGROUND The inflammatory microenvironment plays an essential role in bone healing after fracture. The signaling lymphocytic activation molecule family (SLAMF) members deeply participate in inflammatory response and make a vast difference. METHODS We identified SLAMF8 in GEO datasets (GSE129165 and GSE176086) and co-expression analyses were performed to define the relationships between SLAMF8 and osteogenesis relative genes (RUNX2 and COL1A1). In vitro, we established SLAMF8 knockdown and overexpression mouse bone marrow mesenchymal stem cells (mBMSCs) lines. qPCR, Western blot, ALP staining, ARS staining, Oil Red O staining and Immunofluorescence analyses were performed to investigate the effect of SLAMF8 in mBMSCs osteogenesis and adipogenesis. In vivo, mice femoral fracture model was performed to explore the function of SLAMF8. RESULTS SLAMF8 knockdown significantly suppressed the expression of osteogenesis relative genes (RUNX2, SP7 and COL1A1), ALP activity and mineral deposition, but increased the expression of adipogenesis relative genes (PPARγ and C/EBPα). Additionally, SLAMF8 overexpression had the opposite effects. The role SLAMF8 played in mBMSCs osteogenic and adipogenic differentiation were through S100A6 and Wnt/β-Catenin signaling pathway. Moreover, SLAMF8 overexpression mBMSCs promoted the healing of femoral fracture. CONCLUSIONS SLAMF8 promotes osteogenesis and inhibits adipogenesis of mBMSCs via S100A6 and Wnt/β-Catenin signaling pathway. SLAMF8 overexpression mBMSCs effectively accelerate the healing of femoral fracture in mice.
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Affiliation(s)
- Yibo Wang
- Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, Department of Spinal Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China
| | - Kai Hang
- Department of Orthopaedics, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, 310052, China
| | - Xiaoyong Wu
- Department of Orthopedic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China
- Orthopedics Research Institute of Zhejiang University, Hangzhou, 310009, China
| | - Li Ying
- Department of Orthopedic, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, 317000, China
| | - Zhongxiang Wang
- Department of Orthopedic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China
- Orthopedics Research Institute of Zhejiang University, Hangzhou, 310009, China
| | - Zemin Ling
- Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, Department of Spinal Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China
- Department of Orthopedics, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, 518107, China
| | - Hao Hu
- Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, Department of Spinal Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China
| | - Zhijun Pan
- Department of Orthopedic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China.
- Orthopedics Research Institute of Zhejiang University, Hangzhou, 310009, China.
| | - Xuenong Zou
- Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, Department of Spinal Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China.
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Yokomizo-Goto M, Takenaka-Ninagawa N, Zhao C, Bourgeois Yoshioka CK, Miki M, Motoike S, Inada Y, Zujur D, Theoputra W, Jin Y, Toguchida J, Ikeya M, Sakurai H. Distinct muscle regenerative capacity of human induced pluripotent stem cell-derived mesenchymal stromal cells in Ullrich congenital muscular dystrophy model mice. Stem Cell Res Ther 2024; 15:340. [PMID: 39370505 PMCID: PMC11457425 DOI: 10.1186/s13287-024-03951-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Accepted: 09/18/2024] [Indexed: 10/08/2024] Open
Abstract
BACKGROUND Ullrich congenital muscular dystrophy (UCMD) is caused by a deficiency in type 6 collagen (COL6) due to mutations in COL6A1, COL6A2, or COL6A3. COL6 deficiency alters the extracellular matrix structure and biomechanical properties, leading to mitochondrial defects and impaired muscle regeneration. Therefore, mesenchymal stromal cells (MSCs) that secrete COL6 have attracted attention as potential therapeutic targets. Various tissue-derived MSCs exert therapeutic effects in various diseases. However, no reports have compared the effects of MSCs of different origins on UCMD pathology. METHODS To evaluate which MSC population has the highest therapeutic efficacy for UCMD, in vivo (transplantation of MSCs to Col6a1-KO/NSG mice) and in vitro experiments (muscle stem cell [MuSCs] co-culture with MSCs) were conducted using adipose tissue-derived MSCs, bone marrow-derived MSCs, and xeno-free-induced iPSC-derived MSCs (XF-iMSCs). RESULTS In transplantation experiments on Col6a1-KO/NSG mice, the group transplanted with XF-iMSCs showed significantly enhanced muscle fiber regeneration compared to the other groups 1 week after transplantation. At 12 weeks after transplantation, only the XF-iMSCs transplantation group showed a significantly larger muscle fiber diameter than the other groups without inducing fibrosis, which was observed in the other transplantation groups. Similarly, in co-culture experiments, XF-iMSCs were found to more effectively promote the fusion and differentiation of MuSCs derived from Col6a1-KO/NSG mice than the other primary MSCs investigated in this study. Additionally, in vitro knockdown and supplementation experiments suggested that the IGF2 secreted by XF-iMSCs promoted MuSC differentiation. CONCLUSION XF-iMSCs are promising candidates for promoting muscle regeneration while avoiding fibrosis, offering a safer and more effective therapeutic approach for UCMD than other potential therapies.
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Affiliation(s)
- Megumi Yokomizo-Goto
- Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-Cho, Shogoin, Sakyo-Ku, Kyoto, 606-8507, Japan
| | - Nana Takenaka-Ninagawa
- Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-Cho, Shogoin, Sakyo-Ku, Kyoto, 606-8507, Japan.
- Department of Rehabilitation Medicine, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-Cho, Mizuho-Ku, Nagoya, 467-8601, Japan.
| | - Chengzhu Zhao
- Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-Cho, Shogoin, Sakyo-Ku, Kyoto, 606-8507, Japan
| | - Clémence Kiho Bourgeois Yoshioka
- Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-Cho, Shogoin, Sakyo-Ku, Kyoto, 606-8507, Japan
- Department of Physical Therapy, Human Health Sciences, Graduate School of Medicine, Kyoto University, 53 Kawahara-Cho, Shogoin, Sakyo-Ku, Kyoto, 606-8507, Japan
| | - Mayuho Miki
- Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-Cho, Shogoin, Sakyo-Ku, Kyoto, 606-8507, Japan
- Department of Physical Therapy, Human Health Sciences, Graduate School of Medicine, Kyoto University, 53 Kawahara-Cho, Shogoin, Sakyo-Ku, Kyoto, 606-8507, Japan
| | - Souta Motoike
- Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-Cho, Shogoin, Sakyo-Ku, Kyoto, 606-8507, Japan
| | - Yoshiko Inada
- Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-Cho, Shogoin, Sakyo-Ku, Kyoto, 606-8507, Japan
| | - Denise Zujur
- Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-Cho, Shogoin, Sakyo-Ku, Kyoto, 606-8507, Japan
| | - William Theoputra
- Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-Cho, Shogoin, Sakyo-Ku, Kyoto, 606-8507, Japan
| | - Yonghui Jin
- Department of Regeneration Science and Engineering, Institute for Life and Medical Sciences, Kyoto University, 53 Kawahara-Cho, Shogoin, Sakyo-Ku, Kyoto, 606-8507, Japan
| | - Junya Toguchida
- Department of Regeneration Science and Engineering, Institute for Life and Medical Sciences, Kyoto University, 53 Kawahara-Cho, Shogoin, Sakyo-Ku, Kyoto, 606-8507, Japan
- Department of Fundamental Cell Technology, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-Cho, Shogoin, Sakyo-Ku, Kyoto, 606-8507, Japan
| | - Makoto Ikeya
- Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-Cho, Shogoin, Sakyo-Ku, Kyoto, 606-8507, Japan
| | - Hidetoshi Sakurai
- Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-Cho, Shogoin, Sakyo-Ku, Kyoto, 606-8507, Japan.
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6
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Shamel M, Raafat S, El Karim I, Saber S. Photobiomodulation and low-intensity pulsed ultrasound synergistically enhance dental mesenchymal stem cells viability, migration and differentiation: an invitro study. Odontology 2024; 112:1142-1156. [PMID: 38517569 DOI: 10.1007/s10266-024-00920-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Accepted: 02/18/2024] [Indexed: 03/24/2024]
Abstract
Novel methods and technologies that improve mesenchymal stem cells (MSCs) proliferation and differentiation properties are required to increase their clinical efficacy. Photobiomodulation (PBM) and low-intensity pulsed ultrasound (LIPUS) are two strategies that can be used to enhance the regenerative properties of dental MSCs. This study evaluated the cytocompatibility and osteo/odontogenic differentiation of dental pulp, periodontal ligament, and gingival MSCs after stimulation by either PBM or LIPUS and their combined effect. MTT assay, cell migration assay, osteo/odontogenic differentiation by AR staining and ALP activity, and expression of osteo/odontogenic markers (OPG, OC, RUNX2, DSPP, DMP1) by RT-qPCR were evaluated. Statistical analysis was performed using ANOVA, followed by Tukey's post hoc test, with a p-value of less than 0.05 considered significant. The results showed that combined stimulation by PBM and LIPUS resulted in significantly the highest viability of MSCs, the fastest migration, the most dense AR staining, the most increased ALP activity, and the most elevated levels of osteogenic and odontogenic markers. The synergetic stimulation of PBM and LIPUS can be utilized in cell-based regenerative approaches to promote the properties of dental MSCs.
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Affiliation(s)
- Mohamed Shamel
- Department of Oral Biology, Faculty of Dentistry, The British University in Egypt, El Sherouk City, Egypt
| | - Shereen Raafat
- Department of Pharmacology, Faculty of Dentistry, The British University in Egypt, El Sherouk City, Egypt
- Dental Science Research Group, Health Research Centre of Excellence, The British University in Egypt (BUE), El Sherouk City, Egypt
| | - Ikhlas El Karim
- School of Medicine, Dentistry and Biomedical Sciences, Queen's University, Belfast, UK
| | - Shehabeldin Saber
- Dental Science Research Group, Health Research Centre of Excellence, The British University in Egypt (BUE), El Sherouk City, Egypt.
- Department of Endodontics, Faculty of Dentistry, The British University in Egypt, El Sherouk City, Egypt.
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Peters K, Staehlke S, Rebl H, Jonitz-Heincke A, Hahn O. Impact of Metal Ions on Cellular Functions: A Focus on Mesenchymal Stem/Stromal Cell Differentiation. Int J Mol Sci 2024; 25:10127. [PMID: 39337612 PMCID: PMC11432215 DOI: 10.3390/ijms251810127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Revised: 09/06/2024] [Accepted: 09/18/2024] [Indexed: 09/30/2024] Open
Abstract
Metals play a crucial role in the human body, especially as ions in metalloproteins. Essential metals, such as calcium, iron, and zinc are crucial for various physiological functions, but their interactions within biological networks are complex and not fully understood. Mesenchymal stem/stromal cells (MSCs) are essential for tissue regeneration due to their ability to differentiate into various cell types. This review article addresses the effects of physiological and unphysiological, but not directly toxic, metal ion concentrations, particularly concerning MSCs. Overloading or unbalancing of metal ion concentrations can significantly impair the function and differentiation capacity of MSCs. In addition, excessive or unbalanced metal ion concentrations can lead to oxidative stress, which can affect viability or inflammation. Data on the effects of metal ions on MSC differentiation are limited and often contradictory. Future research should, therefore, aim to clarify the mechanisms by which metal ions affect MSC differentiation, focusing on aspects such as metal ion interactions, ion concentrations, exposure duration, and other environmental conditions. Understanding these interactions could ultimately improve the design of biomaterials and implants to promote MSC-mediated tissue regeneration. It could also lead to the development of innovative therapeutic strategies in regenerative medicine.
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Affiliation(s)
- Kirsten Peters
- Institute of Cell Biology, Rostock University Medical Center Rostock, Schillingallee 69, 18057 Rostock, Germany; (S.S.); (H.R.); (O.H.)
| | - Susanne Staehlke
- Institute of Cell Biology, Rostock University Medical Center Rostock, Schillingallee 69, 18057 Rostock, Germany; (S.S.); (H.R.); (O.H.)
| | - Henrike Rebl
- Institute of Cell Biology, Rostock University Medical Center Rostock, Schillingallee 69, 18057 Rostock, Germany; (S.S.); (H.R.); (O.H.)
| | - Anika Jonitz-Heincke
- Research Laboratory for Biomechanics and Implant Technology, Department of Orthopaedics, Rostock University Medical Center, Doberaner Strasse 142, 18057 Rostock, Germany;
| | - Olga Hahn
- Institute of Cell Biology, Rostock University Medical Center Rostock, Schillingallee 69, 18057 Rostock, Germany; (S.S.); (H.R.); (O.H.)
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Hang K, Wang Y, Bai J, Wang Z, Wu W, Zhu W, Liu S, Pan Z, Chen J, Chen W. Chaperone-mediated autophagy protects the bone formation from excessive inflammation through PI3K/AKT/GSK3β/β-catenin pathway. FASEB J 2024; 38:e23646. [PMID: 38795328 DOI: 10.1096/fj.202302425r] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2023] [Revised: 02/06/2024] [Accepted: 04/22/2024] [Indexed: 05/27/2024]
Abstract
Multiple regulatory mechanisms are in place to ensure the normal processes of bone metabolism, encompassing both bone formation and absorption. This study has identified chaperone-mediated autophagy (CMA) as a critical regulator that safeguards bone formation from the detrimental effects of excessive inflammation. By silencing LAMP2A or HSCA8, we observed a hindrance in the osteoblast differentiation of human bone marrow mesenchymal stem cells (hBMSCs) in vitro. To further elucidate the role of LAMP2A, we generated LAMP2A gene knockdown and overexpression of mouse BMSCs (mBMSCs) using adenovirus. Our results showed that LAMP2A knockdown led to a decrease in osteogenic-specific proteins, while LAMP2A overexpression favored the osteogenesis of mBMSCs. Notably, active-β-catenin levels were upregulated by LAMP2A overexpression. Furthermore, we found that LAMP2A overexpression effectively protected the osteogenesis of mBMSCs from TNF-α, through the PI3K/AKT/GSK3β/β-catenin pathway. Additionally, LAMP2A overexpression significantly inhibited osteoclast hyperactivity induced by TNF-α. Finally, in a murine bone defect model, we demonstrated that controlled release of LAMP2A overexpression adenovirus by alginate sodium capsule efficiently protected bone healing from inflammation, as confirmed by imaging and histological analyses. Collectively, our findings suggest that enhancing CMA has the potential to safeguard bone formation while mitigating hyperactivity in bone absorption.
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Affiliation(s)
- Kai Hang
- Department of Orthopaedics, the Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Zhejiang, Hangzhou, China
| | - YiBo Wang
- Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - JinWu Bai
- Department of Orthopedics, Peking University Third Hospital, Beijing, China
| | - ZhongXiang Wang
- Department of Orthopedic Surgery of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - WeiLiang Wu
- Department of Orthopaedics, the Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Zhejiang, Hangzhou, China
| | - WeiWei Zhu
- Department of Orthopaedics, the Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Zhejiang, Hangzhou, China
| | - ShuangAi Liu
- Department of Pediatric Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - ZhiJun Pan
- Department of Orthopedic Surgery of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - JianSong Chen
- Department of Orthopaedics, the Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Zhejiang, Hangzhou, China
| | - WenHao Chen
- Department of Orthopaedics, the Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Zhejiang, Hangzhou, China
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9
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Zhang S, Lee Y, Liu Y, Yu Y, Han I. Stem Cell and Regenerative Therapies for the Treatment of Osteoporotic Vertebral Compression Fractures. Int J Mol Sci 2024; 25:4979. [PMID: 38732198 PMCID: PMC11084822 DOI: 10.3390/ijms25094979] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2024] [Revised: 04/28/2024] [Accepted: 04/30/2024] [Indexed: 05/13/2024] Open
Abstract
Osteoporotic vertebral compression fractures (OVCFs) significantly increase morbidity and mortality, presenting a formidable challenge in healthcare. Traditional interventions such as vertebroplasty and kyphoplasty, despite their widespread use, are limited in addressing the secondary effects of vertebral fractures in adjacent areas and do not facilitate bone regeneration. This review paper explores the emerging domain of regenerative therapies, spotlighting stem cell therapy's transformative potential in OVCF treatment. It thoroughly describes the therapeutic possibilities and mechanisms of action of mesenchymal stem cells against OVCFs, relying on recent clinical trials and preclinical studies for efficacy assessment. Our findings reveal that stem cell therapy, particularly in combination with scaffolding materials, holds substantial promise for bone regeneration, spinal stability improvement, and pain mitigation. This integration of stem cell-based methods with conventional treatments may herald a new era in OVCF management, potentially improving patient outcomes. This review advocates for accelerated research and collaborative efforts to translate laboratory breakthroughs into clinical practice, emphasizing the revolutionary impact of regenerative therapies on OVCF management. In summary, this paper positions stem cell therapy at the forefront of innovation for OVCF treatment, stressing the importance of ongoing research and cross-disciplinary collaboration to unlock its full clinical potential.
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Affiliation(s)
- Songzi Zhang
- Department of Neurosurgery, CHA Bundang Medical Center, CHA University, Seongnam-si 13496, Republic of Korea; (S.Z.); (Y.L.); (Y.Y.)
| | - Yunhwan Lee
- Department of Medicine, School of Medicine, CHA University, Seongnam-si 13496, Republic of Korea;
| | - Yanting Liu
- Department of Neurosurgery, CHA Bundang Medical Center, CHA University, Seongnam-si 13496, Republic of Korea; (S.Z.); (Y.L.); (Y.Y.)
| | - Yerin Yu
- Department of Neurosurgery, CHA Bundang Medical Center, CHA University, Seongnam-si 13496, Republic of Korea; (S.Z.); (Y.L.); (Y.Y.)
| | - Inbo Han
- Department of Neurosurgery, CHA Bundang Medical Center, CHA University, Seongnam-si 13496, Republic of Korea; (S.Z.); (Y.L.); (Y.Y.)
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10
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Jia S, Liang R, Chen J, Liao S, Lin J, Li W. Emerging technology has a brilliant future: the CRISPR-Cas system for senescence, inflammation, and cartilage repair in osteoarthritis. Cell Mol Biol Lett 2024; 29:64. [PMID: 38698311 PMCID: PMC11067114 DOI: 10.1186/s11658-024-00581-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Accepted: 04/19/2024] [Indexed: 05/05/2024] Open
Abstract
Osteoarthritis (OA), known as one of the most common types of aseptic inflammation of the musculoskeletal system, is characterized by chronic pain and whole-joint lesions. With cellular and molecular changes including senescence, inflammatory alterations, and subsequent cartilage defects, OA eventually leads to a series of adverse outcomes such as pain and disability. CRISPR-Cas-related technology has been proposed and explored as a gene therapy, offering potential gene-editing tools that are in the spotlight. Considering the genetic and multigene regulatory mechanisms of OA, we systematically review current studies on CRISPR-Cas technology for improving OA in terms of senescence, inflammation, and cartilage damage and summarize various strategies for delivering CRISPR products, hoping to provide a new perspective for the treatment of OA by taking advantage of CRISPR technology.
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Affiliation(s)
- Shicheng Jia
- Department of Sports Medicine and Rehabilitation, Peking University Shenzhen Hospital, Shenzhen, 518036, China
- Shantou University Medical College, Shantou, 515041, China
| | - Rongji Liang
- Shantou University Medical College, Shantou, 515041, China
| | - Jiayou Chen
- Department of Sports Medicine and Rehabilitation, Peking University Shenzhen Hospital, Shenzhen, 518036, China
- Shantou University Medical College, Shantou, 515041, China
| | - Shuai Liao
- Department of Bone and Joint, Peking University Shenzhen Hospital, Shenzhen, 518036, China
- Shenzhen University School of Medicine, Shenzhen, 518060, China
| | - Jianjing Lin
- Department of Sports Medicine and Rehabilitation, Peking University Shenzhen Hospital, Shenzhen, 518036, China.
| | - Wei Li
- Department of Sports Medicine and Rehabilitation, Peking University Shenzhen Hospital, Shenzhen, 518036, China.
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11
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Maged G, Abdelsamed MA, Wang H, Lotfy A. The potency of mesenchymal stem/stromal cells: does donor sex matter? Stem Cell Res Ther 2024; 15:112. [PMID: 38644508 PMCID: PMC11034072 DOI: 10.1186/s13287-024-03722-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2024] [Accepted: 04/05/2024] [Indexed: 04/23/2024] Open
Abstract
Mesenchymal stem/stromal cells (MSCs) are a promising therapeutic tool in cell therapy and tissue engineering because of their multi-lineage differentiation capacity, immunomodulatory effects, and tissue protective potential. To achieve optimal results as a therapeutic tool, factors affecting MSC potency, including but not limited to cell source, donor age, and cell batch, have been investigated. Although the sex of the donor has been attributed as a potential factor that can influence MSC potency and efficacy, the impact of donor sex on MSC characteristics has not been carefully investigated. In this review, we summarize published studies demonstrating donor-sex-related MSC heterogeneity and emphasize the importance of disclosing donor sex as a key factor affecting MSC potency in cell therapy.
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Affiliation(s)
- Ghada Maged
- Department of Biochemistry, Faculty of Science, Alexandria University, Alexandria, Egypt
| | - Menna A Abdelsamed
- Biotechnology and Life Sciences Department, Faculty of Postgraduate studies for Advanced Sciences, Beni-Suef University, Beni Suef, Egypt
| | - Hongjun Wang
- Department of Surgery, Medical University of South Carolina, 29425, Charleston, SC, USA.
- Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC, USA.
| | - Ahmed Lotfy
- Department of Surgery, Medical University of South Carolina, 29425, Charleston, SC, USA.
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12
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Sharif H, Ziaei H, Rezaei N. Stem Cell-Based Regenerative Approaches for the Treatment of Cleft Lip and Palate: A Comprehensive Review. Stem Cell Rev Rep 2024; 20:637-655. [PMID: 38270744 DOI: 10.1007/s12015-024-10676-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/08/2024] [Indexed: 01/26/2024]
Abstract
Cleft lip and/or palate (CLP) is a prevalent congenital craniofacial abnormality that can lead to difficulties in eating, speaking, hearing, and psychological distress. The traditional approach for treating CLP involves bone graft surgery, which has limitations, post-surgical complications, and donor site morbidity. However, regenerative medicine has emerged as a promising alternative, employing a combination of stem cells, growth factors, and scaffolds to promote tissue regeneration. This review aims to provide a comprehensive overview of stem cell-based regenerative approaches in the management of CLP. A thorough search was conducted in the Medline/PubMed and Scopus databases, including cohort studies, randomized controlled trials, case series, case controls, case reports, and animal studies. The identified studies were categorized into two main groups: clinical studies involving human subjects and in vivo studies using animal models. While there are only a limited number of studies investigating the combined use of stem cells and scaffolds for CLP treatment, they have shown promising results. Various types of stem cells have been utilized in conjunction with scaffolds. Importantly, regenerative methods have been successfully applied to patients across a broad range of age groups. The collective findings derived from the reviewed studies consistently support the notion that regenerative medicine holds potential advantages over conventional bone grafting and represents a promising therapeutic option for CLP. However, future well-designed clinical trials, encompassing diverse combinations of stem cells and scaffolds, are warranted to establish the clinical efficacy of these interventions with a larger number of patients.
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Affiliation(s)
- Helia Sharif
- Universal Scientific Education and Research Network (USERN), Tehran, Iran
- Dental Society, Faculty of Dentistry, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Heliya Ziaei
- Universal Scientific Education and Research Network (USERN), Tehran, Iran
- Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, US
| | - Nima Rezaei
- Universal Scientific Education and Research Network (USERN), Tehran, Iran.
- Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
- Children's Medical Center Hospital, Dr. Qarib St, Keshavarz Blvd, Tehran, 14194, Iran.
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13
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Gao Q, Liu J, Wang M, Liu X, Jiang Y, Su J. Biomaterials regulates BMSCs differentiation via mechanical microenvironment. BIOMATERIALS ADVANCES 2024; 157:213738. [PMID: 38154401 DOI: 10.1016/j.bioadv.2023.213738] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/08/2023] [Revised: 12/11/2023] [Accepted: 12/16/2023] [Indexed: 12/30/2023]
Abstract
Bone mesenchymal stem cells (BMSCs) are crucial for bone tissue regeneration, the mechanical microenvironment of hard tissues, including bone and teeth, significantly affects the osteogenic differentiation of BMSCs. Biomaterials may mimic the microenvironment of the extracellular matrix and provide mechanical signals to regulate BMSCs differentiation via inducing the secretion of various intracellular factors. Biomaterials direct the differentiation of BMSCs via mechanical signals, including tension, compression, shear, hydrostatic pressure, stiffness, elasticity, and viscoelasticity, which can be transmitted to cells through mechanical signalling pathways. Besides, biomaterials with piezoelectric effects regulate BMSCs differentiation via indirect mechanical signals, such as, electronic signals, which are transformed from mechanical stimuli by piezoelectric biomaterials. Mechanical stimulation facilitates achieving vectored stem cell fate regulation, while understanding the underlying mechanisms remains challenging. Herein, this review summarizes the intracellular factors, including translation factors, epigenetic modifications, and miRNA level, as well as the extracellular factor, including direct and indirect mechanical signals, which regulate the osteogenic differentiation of BMSCs. Besides, this review will also give a comprehensive summary about how mechanical stimuli regulate cellular behaviours, as well as how biomaterials promote the osteogenic differentiation of BMSCs via mechanical microenvironments. The cellular behaviours and activated signal pathways will give more implications for the design of biomaterials with superior properties for bone tissue engineering. Moreover, it will also provide inspiration for the construction of bone organoids which is a useful tool for mimicking in vivo bone tissue microenvironments.
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Affiliation(s)
- Qianmin Gao
- Institute of Translational Medicine, Shanghai University, NO.333 Nanchen Road, Shanghai 200444, PR China; Organoid Research Centre, Shanghai University, NO.333 Nanchen Road, Shanghai 200444, PR China; National Centre for Translational Medicine (Shanghai) SHU Branch, NO.333 Nanchen Road, Shanghai University, Shanghai 200444, PR China
| | - Jinlong Liu
- Institute of Translational Medicine, Shanghai University, NO.333 Nanchen Road, Shanghai 200444, PR China; Organoid Research Centre, Shanghai University, NO.333 Nanchen Road, Shanghai 200444, PR China; National Centre for Translational Medicine (Shanghai) SHU Branch, NO.333 Nanchen Road, Shanghai University, Shanghai 200444, PR China
| | - Mingkai Wang
- Institute of Translational Medicine, Shanghai University, NO.333 Nanchen Road, Shanghai 200444, PR China; Organoid Research Centre, Shanghai University, NO.333 Nanchen Road, Shanghai 200444, PR China; National Centre for Translational Medicine (Shanghai) SHU Branch, NO.333 Nanchen Road, Shanghai University, Shanghai 200444, PR China
| | - Xiangfei Liu
- Department of Orthopedics, Shanghai Zhongye Hospital, NO. 456 Chunlei Road, Shanghai 200941, PR China.
| | - Yingying Jiang
- Institute of Translational Medicine, Shanghai University, NO.333 Nanchen Road, Shanghai 200444, PR China.
| | - Jiacan Su
- Institute of Translational Medicine, Shanghai University, NO.333 Nanchen Road, Shanghai 200444, PR China; Organoid Research Centre, Shanghai University, NO.333 Nanchen Road, Shanghai 200444, PR China; National Centre for Translational Medicine (Shanghai) SHU Branch, NO.333 Nanchen Road, Shanghai University, Shanghai 200444, PR China; Department of Orthopedics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, NO.1665 Kongjiang Road, Shanghai 200092, PR China.
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14
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Kaviarasan V, Deka D, Balaji D, Pathak S, Banerjee A. Signaling Pathways in Trans-differentiation of Mesenchymal Stem Cells: Recent Advances. Methods Mol Biol 2024; 2736:207-223. [PMID: 37140811 DOI: 10.1007/7651_2023_478] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/05/2023]
Abstract
Mesenchymal stem cells are a group of multipotent cells that can be induced to differentiate into other cell types. The cells fate is decided by various signaling pathways, growth factors, and transcription factors in differentiation. The proper coordination of these factors will result in cell specification. MSCs are capable of being differentiated into osteogenic, chondrogenic, and adipogenic lineages. Different conditions induces the MSCs into particular phenotypes. The MSC trans-differentiation ensues as a response to environmental factors or due to circumstances that prove to favor trans-differentiation. Depending on the stage at which they are expressed, and the genetic alterations they undergo prior to their expression, transcription factors can accelerate the process of trans-differentiation. Further research has been conducted on the challenging aspect of MSCs being developed into non-mesenchymal lineage. The cells that are differentiated in this way maintain their stability even after being induced in animals. The recent advancements in the trans-differentiation capacities of MSCs on induction with chemicals, growth inducers, improved differentiation mediums, growth factors from plant extracts, and electrical stimulation are discussed in this paper. Signaling pathways have a great effect on MSCs trans-differentiation and they need to be better understood for their applications in therapeutic techniques. So, this paper tends to review the major signaling pathways that play a vital role in the trans-differentiation of MSC.
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Affiliation(s)
- Vaishak Kaviarasan
- Department of Medical Biotechnology, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI), Chennai, India
| | - Dikshita Deka
- Department of Medical Biotechnology, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI), Chennai, India
| | - Darshini Balaji
- Department of Medical Biotechnology, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI), Chennai, India
| | - Surajit Pathak
- Department of Medical Biotechnology, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI), Chennai, India
| | - Antara Banerjee
- Department of Medical Biotechnology, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI), Chennai, India.
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15
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Wang X, Li N, Zheng M, Yu Y, Zhang S. Acetylation and deacetylation of histone in adipocyte differentiation and the potential significance in cancer. Transl Oncol 2024; 39:101815. [PMID: 37935080 PMCID: PMC10654249 DOI: 10.1016/j.tranon.2023.101815] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Revised: 10/17/2023] [Accepted: 10/22/2023] [Indexed: 11/09/2023] Open
Abstract
Adipocytes are derived from pluripotent mesenchymal stem cells and can develop into several cell types including adipocytes, myocytes, chondrocytes, and osteocytes. Adipocyte differentiation is regulated by a variety of transcription factors and signaling pathways. Various epigenetic factors, particularly histone modifications, play key roles in adipocyte differentiation and have indispensable functions in altering chromatin conformation. Histone acetylases and deacetylases participate in the regulation of protein acetylation, mediate transcriptional and post-translational modifications, and directly acetylate or deacetylate various transcription factors and regulatory proteins. The adipocyte differentiation of stem cells plays a key role in various metabolic diseases. Cancer stem cells(CSCs) play an important function in cancer metastasis, recurrence, and drug resistance, and have the characteristics of stem cells. They are expressed in various cell lineages, including adipocytes. Recent studies have shown that cancer stem cells that undergo epithelial-mesenchymal transformation can undergo adipocytic differentiation, thereby reducing the degree of malignancy. This opens up new possibilities for cancer treatment. This review summarizes the regulation of acetylation during adipocyte differentiation, involving the functions of histone acetylating and deacetylating enzymes as well as non-histone acetylation modifications. Mechanistic studies on adipogenesis and acetylation during the differentiation of cancer cells into a benign cell phenotype may help identify new targets for cancer treatment.
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Affiliation(s)
- Xiaorui Wang
- Department of Pathology, Tianjin Union Medical Center, Nankai University, Tianjin 300121, China; Graduate School, Tianjin Medical University, Tianjin 300070, China
| | - Na Li
- Department of Pathology, Tianjin Union Medical Center, Nankai University, Tianjin 300121, China; Graduate School, Tianjin Medical University, Tianjin 300070, China
| | - Minying Zheng
- Department of Pathology, Tianjin Union Medical Center, Nankai University, Tianjin 300121, China
| | - Yongjun Yu
- Department of Pathology, Tianjin Union Medical Center, Nankai University, Tianjin 300121, China
| | - Shiwu Zhang
- Department of Pathology, Tianjin Union Medical Center, Nankai University, Tianjin 300121, China.
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16
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Fasciano S, Luo S, Wang S. Long non-coding RNA (lncRNA) MALAT1 in regulating osteogenic and adipogenic differentiation using a double-stranded gapmer locked nucleic acid nanobiosensor. Analyst 2023; 148:6261-6273. [PMID: 37937546 DOI: 10.1039/d3an01531a] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2023]
Abstract
Long non-coding RNAs (lncRNA) are non-protein coding RNA molecules that are longer than 200 nucleotides. The lncRNA molecule plays diverse roles in gene regulation, chromatin remodeling, and cellular processes, influencing various biological pathways. However, probing the complex dynamics of lncRNA in live cells is a challenging task. In this study, a double-stranded gapmer locked nucleic acid (ds-GapM-LNA) nanobiosensor is designed for visualizing the abundance and expression of lncRNA in live human bone-marrow-derived mesenchymal stem cells (hMSCs). The sensitivity, specificity, and stability were characterized. The results showed that this ds-GapM-LNA nanobiosensor has very good sensitivity, specificity, and stability, which allows for dissecting the regulatory roles of cellular processes during dynamic physiological events. By incorporating this nanobiosensor in living hMSC imaging, we elucidated lncRNA MALAT1 expression dynamics during osteogenic and adipogenic differentiation. The data reveal that lncRNA MALAT1 expression is correlated with distinct sub-stages of osteogenic and adipogenic differentiation.
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Affiliation(s)
- Samantha Fasciano
- Department of Chemistry, Chemical and Biomedical Engineering, Tagliatela College of Engineering, University of New Haven, West Haven, CT, 06516, USA.
- Department of Cellular and Molecular Biology, College of Art and Science, University of New Haven, West Haven, CT, 06516, USA
| | - Shuai Luo
- Department of Chemistry, Chemical and Biomedical Engineering, Tagliatela College of Engineering, University of New Haven, West Haven, CT, 06516, USA.
| | - Shue Wang
- Department of Chemistry, Chemical and Biomedical Engineering, Tagliatela College of Engineering, University of New Haven, West Haven, CT, 06516, USA.
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17
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Deering J, Mahmoud D, Rier E, Lin Y, do Nascimento Pereira AC, Titotto S, Fang Q, Wohl GR, Deng F, Grandfield K, Elbestawi MA, Chen J. Osseointegration of functionally graded Ti6Al4V porous implants: Histology of the pore network. BIOMATERIALS ADVANCES 2023; 155:213697. [PMID: 37979439 DOI: 10.1016/j.bioadv.2023.213697] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Revised: 10/11/2023] [Accepted: 11/05/2023] [Indexed: 11/20/2023]
Abstract
The additive manufacturing of titanium into porous geometries offers a means to generate low-stiffness endosseous implants with a greater surface area available for osseointegration. In this work, selective laser melting was used to produce gyroid-based scaffolds with a uniform pore size of 300 μm or functionally graded pore size from 600 μm to 300 μm. Initial in vitro assessment with Saos-2 cells showed favourable cell proliferation at pore sizes of 300 and 600 μm. Following implantation into rabbit tibiae, early histological observations at four weeks indicated some residual inflammation alongside neovessel infiltration into the scaffold interior and some early apposition of mineralized bone tissue. At twelve weeks, both scaffolds were filled with a mixture of adipocyte-rich marrow, micro-capillaries, and mineralized bone tissue. X-ray microcomputed tomography showed a higher bone volume fraction (BV/TV) and percentage of bone-implant contact (BIC) in the implants with 300 μm pores than in the functionally graded specimens. In functionally graded specimens, localized BV/TV measurement was observed to be higher in the innermost region containing smaller pores (estimated at 300-400 μm) than in larger pores at the implant exterior. The unit cell topology of the porous implant was also observed to guide the direction of bone ingrowth by conducting along the implant struts. These results suggest that in vivo experimentation is necessary alongside parametric optimization of functionally graded porous implants to predict short-term and long-term bone apposition.
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Affiliation(s)
- Joseph Deering
- Department of Materials Science and Engineering, McMaster University, Hamilton, ON, Canada
| | - Dalia Mahmoud
- Department of Mechanical Engineering, McMaster University, Hamilton, ON, Canada; Production Engineering Department, Faculty of Engineering, Alexandria University, Alexandria 21544, Egypt
| | - Elyse Rier
- School of Biomedical Engineering, McMaster University, Hamilton, ON, Canada
| | - Yujing Lin
- Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, China
| | - Anna Cecilia do Nascimento Pereira
- Center of Engineering, Modeling and Applied Social Sciences, Federal University of ABC (UFABC), Santo André, Brazil; 4D Printing and Biomimetics' (4DB) Research Group, Federal University of ABC (UFABC), Santo André, Brazil
| | - Silvia Titotto
- Center of Engineering, Modeling and Applied Social Sciences, Federal University of ABC (UFABC), Santo André, Brazil; 4D Printing and Biomimetics' (4DB) Research Group, Federal University of ABC (UFABC), Santo André, Brazil
| | - Qiyin Fang
- Department of Engineering Physics, McMaster University, Hamilton, ON, Canada
| | - Gregory R Wohl
- Department of Mechanical Engineering, McMaster University, Hamilton, ON, Canada; School of Biomedical Engineering, McMaster University, Hamilton, ON, Canada; Brockhouse Institute for Materials Research, McMaster University, Hamilton, ON, Canada
| | - Feilong Deng
- Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, China
| | - Kathryn Grandfield
- Department of Materials Science and Engineering, McMaster University, Hamilton, ON, Canada; School of Biomedical Engineering, McMaster University, Hamilton, ON, Canada; Brockhouse Institute for Materials Research, McMaster University, Hamilton, ON, Canada.
| | - Mohamed A Elbestawi
- Department of Mechanical Engineering, McMaster University, Hamilton, ON, Canada.
| | - Jianyu Chen
- Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, China.
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18
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Mai M, Luo S, Fasciano S, Oluwole TE, Ortiz J, Pang Y, Wang S. Morphology-based deep learning approach for predicting adipogenic and osteogenic differentiation of human mesenchymal stem cells (hMSCs). Front Cell Dev Biol 2023; 11:1329840. [PMID: 38099293 PMCID: PMC10720363 DOI: 10.3389/fcell.2023.1329840] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Accepted: 11/17/2023] [Indexed: 12/17/2023] Open
Abstract
Human mesenchymal stem cells (hMSCs) are multipotent progenitor cells with the potential to differentiate into various cell types, including osteoblasts, chondrocytes, and adipocytes. These cells have been extensively employed in the field of cell-based therapies and regenerative medicine due to their inherent attributes of self-renewal and multipotency. Traditional approaches for assessing hMSCs differentiation capacity have relied heavily on labor-intensive techniques, such as RT-PCR, immunostaining, and Western blot, to identify specific biomarkers. However, these methods are not only time-consuming and economically demanding, but also require the fixation of cells, resulting in the loss of temporal data. Consequently, there is an emerging need for a more efficient and precise approach to predict hMSCs differentiation in live cells, particularly for osteogenic and adipogenic differentiation. In response to this need, we developed innovative approaches that combine live-cell imaging with cutting-edge deep learning techniques, specifically employing a convolutional neural network (CNN) to meticulously classify osteogenic and adipogenic differentiation. Specifically, four notable pre-trained CNN models, VGG 19, Inception V3, ResNet 18, and ResNet 50, were developed and tested for identifying adipogenic and osteogenic differentiated cells based on cell morphology changes. We rigorously evaluated the performance of these four models concerning binary and multi-class classification of differentiated cells at various time intervals, focusing on pivotal metrics such as accuracy, the area under the receiver operating characteristic curve (AUC), sensitivity, precision, and F1-score. Among these four different models, ResNet 50 has proven to be the most effective choice with the highest accuracy (0.9572 for binary, 0.9474 for multi-class) and AUC (0.9958 for binary, 0.9836 for multi-class) in both multi-class and binary classification tasks. Although VGG 19 matched the accuracy of ResNet 50 in both tasks, ResNet 50 consistently outperformed it in terms of AUC, underscoring its superior effectiveness in identifying differentiated cells. Overall, our study demonstrated the capability to use a CNN approach to predict stem cell fate based on morphology changes, which will potentially provide insights for the application of cell-based therapy and advance our understanding of regenerative medicine.
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Affiliation(s)
- Maxwell Mai
- Department of Mathematics, Southern Connecticut State University, New Haven, CT, United States
| | - Shuai Luo
- Department of Chemistry, Chemical and Biomedical Engineering, University of New Haven, West Haven, CT, United States
| | - Samantha Fasciano
- Department of Cellular and Molecular Biology, University of New Haven, West Haven, CT, United States
| | - Timilehin Esther Oluwole
- Department of Chemistry, Chemical and Biomedical Engineering, University of New Haven, West Haven, CT, United States
| | - Justin Ortiz
- Department of Mechanical and Industrial Engineering, University of New Haven, West Haven, CT, United States
| | - Yulei Pang
- Department of Mathematics, Southern Connecticut State University, New Haven, CT, United States
| | - Shue Wang
- Department of Chemistry, Chemical and Biomedical Engineering, University of New Haven, West Haven, CT, United States
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19
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Zhang L, Guan Q, Wang Z, Feng J, Zou J, Gao B. Consequences of Aging on Bone. Aging Dis 2023; 15:2417-2452. [PMID: 38029404 PMCID: PMC11567267 DOI: 10.14336/ad.2023.1115] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2023] [Accepted: 11/16/2023] [Indexed: 12/01/2023] Open
Abstract
With the aging of the global population, the incidence of musculoskeletal diseases has been increasing, seriously affecting people's health. As people age, the microenvironment within skeleton favors bone resorption and inhibits bone formation, accompanied by bone marrow fat accumulation and multiple cellular senescence. Specifically, skeletal stem/stromal cells (SSCs) during aging tend to undergo adipogenesis rather than osteogenesis. Meanwhile, osteoblasts, as well as osteocytes, showed increased apoptosis, decreased quantity, and multiple functional limitations including impaired mechanical sensing, intercellular modulation, and exosome secretion. Also, the bone resorption function of macrophage-lineage cells (including osteoclasts and preosteoclasts) was significantly enhanced, as well as impaired vascularization and innervation. In this study, we systematically reviewed the effect of aging on bone and the within microenvironment (including skeletal cells as well as their intracellular structure variations, vascular structures, innervation, marrow fat distribution, and lymphatic system) caused by aging, and mechanisms of osteoimmune regulation of the bone environment in the aging state, and the causal relationship with multiple musculoskeletal diseases in addition with their potential therapeutic strategy.
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Affiliation(s)
- Lingli Zhang
- College of Athletic Performance, Shanghai University of Sport, Shanghai, China
| | - Qiao Guan
- School of Exercise and Health, Shanghai University of Sport, Shanghai, China
| | - Zhikun Wang
- School of Exercise and Health, Shanghai University of Sport, Shanghai, China
| | - Jie Feng
- School of Exercise and Health, Shanghai University of Sport, Shanghai, China
| | - Jun Zou
- School of Exercise and Health, Shanghai University of Sport, Shanghai, China
| | - Bo Gao
- Department of Orthopedic Surgery, Xijing Hospital, Air Force Medical University, Xi’an, China
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20
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Estévez M, Cicuéndez M, Crespo J, Serrano-López J, Colilla M, Fernández-Acevedo C, Oroz-Mateo T, Rada-Leza A, González B, Izquierdo-Barba I, Vallet-Regí M. Large-scale production of superparamagnetic iron oxide nanoparticles by flame spray pyrolysis: In vitro biological evaluation for biomedical applications. J Colloid Interface Sci 2023; 650:560-572. [PMID: 37429163 DOI: 10.1016/j.jcis.2023.07.009] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Revised: 06/21/2023] [Accepted: 07/03/2023] [Indexed: 07/12/2023]
Abstract
Despite the large number of synthesis methodologies described for superparamagnetic iron oxide nanoparticles (SPIONs), the search for their large-scale production for their widespread use in biomedical applications remains a mayor challenge. Flame Spray Pyrolysis (FSP) could be the solution to solve this limitation, since it allows the fabrication of metal oxide nanoparticles with high production yield and low manufacture costs. However, to our knowledge, to date such fabrication method has not been upgraded for biomedical purposes. Herein, SPIONs have been fabricated by FSP and their surface has been treated to be subsequently coated with dimercaptosuccinic acid (DMSA) to enhance their colloidal stability in aqueous media. The final material presents high quality in terms of nanoparticle size, homogeneous size distribution, long-term colloidal stability and magnetic properties. A thorough in vitro validation has been performed with peripheral blood cells and mesenchymal stem cells (hBM-MSCs). Specifically, hemocompatibility studies show that these functionalized FSP-SPIONs-DMSA nanoparticles do not cause platelet aggregation or impair basal monocyte function. Moreover, in vitro biocompatibility assays show a dose-dependent cellular uptake while maintaining high cell viability values and cell cycle progression without causing cellular oxidative stress. Taken together, the results suggest that the FSP-SPIONs-DMSA optimized in this work could be a worthy alternative with the benefit of a large-scale production aimed at industrialization for biomedical applications.
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Affiliation(s)
- Manuel Estévez
- Departamento de Química en Ciencias Farmacéuticas, Facultad de Farmacia, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria, Hospital 12 de Octubre i+12, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain.
| | - Mónica Cicuéndez
- Departamento de Química en Ciencias Farmacéuticas, Facultad de Farmacia, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, Spain.
| | - Julián Crespo
- Tecnología Navarra de Nanoproductos S.L. (TECNAN), área industrial PERGUITA, C/A, N° 1, 31210 Los Arcos (Navarra), Spain.
| | - Juana Serrano-López
- Experimental Hematology Lab, IIS- Fundación Jiménez Díaz, UAM, Madrid 28040, Spain.
| | - Montserrat Colilla
- Departamento de Química en Ciencias Farmacéuticas, Facultad de Farmacia, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria, Hospital 12 de Octubre i+12, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain; Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Spain.
| | - Claudio Fernández-Acevedo
- Centro Tecnológico ĹUrederra, área industrial PERGUITA, C/A, N° 1, 31210 Los Arcos (Navarra), Spain.
| | - Tamara Oroz-Mateo
- Centro Tecnológico ĹUrederra, área industrial PERGUITA, C/A, N° 1, 31210 Los Arcos (Navarra), Spain.
| | - Amaia Rada-Leza
- Centro Tecnológico ĹUrederra, área industrial PERGUITA, C/A, N° 1, 31210 Los Arcos (Navarra), Spain.
| | - Blanca González
- Departamento de Química en Ciencias Farmacéuticas, Facultad de Farmacia, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria, Hospital 12 de Octubre i+12, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain; Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Spain.
| | - Isabel Izquierdo-Barba
- Departamento de Química en Ciencias Farmacéuticas, Facultad de Farmacia, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria, Hospital 12 de Octubre i+12, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain; Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Spain.
| | - María Vallet-Regí
- Departamento de Química en Ciencias Farmacéuticas, Facultad de Farmacia, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria, Hospital 12 de Octubre i+12, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain; Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Spain.
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21
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Zhang A, Wong JKU, Redzikultsava K, Baldry M, Alavi SK, Wang Z, van Koten E, Weiss A, Bilek M, Yeo GC, Akhavan B. A cost-effective and enhanced mesenchymal stem cell expansion platform with internal plasma-activated biofunctional interfaces. Mater Today Bio 2023; 22:100727. [PMID: 37529421 PMCID: PMC10388840 DOI: 10.1016/j.mtbio.2023.100727] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2023] [Revised: 06/30/2023] [Accepted: 07/07/2023] [Indexed: 08/03/2023] Open
Abstract
Mesenchymal stem cells (MSCs) used for clinical applications require in vitro expansion to achieve therapeutically relevant numbers. However, conventional planar cell expansion approaches using tissue culture vessels are inefficient, costly, and can trigger MSC phenotypic and functional decline. Here we present a one-step dry plasma process to modify the internal surfaces of three-dimensional (3D) printed, high surface area to volume ratio (high-SA:V) porous scaffolds as platforms for stem cell expansion. To address the long-lasting challenge of uniform plasma treatment within the micrometre-sized pores of scaffolds, we developed a packed bed plasma immersion ion implantation (PBPI3) technology by which plasma is ignited inside porous materials for homogeneous surface activation. COMSOL Multiphysics simulations support our experimental data and provide insights into the role of electrical field and pressure distribution in plasma ignition. Spatial surface characterisation inside scaffolds demonstrates the homogeneity of PBPI3 activation. The PBPI3 treatment induces radical-containing chemical structures that enable the covalent attachment of biomolecules via a simple, non-toxic, single-step incubation process. We showed that PBPI3-treated scaffolds biofunctionalised with fibroblast growth factor 2 (FGF2) significantly promoted the expansion of MSCs, preserved cell phenotypic expression, and multipotency, while reducing the usage of costly growth factor supplements. This breakthrough PBPI3 technology can be applied to a wide range of 3D polymeric porous scaffolds, paving the way towards developing new biomimetic interfaces for tissue engineering and regenerative medicine.
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Affiliation(s)
- Anyu Zhang
- School of Biomedical Engineering, University of Sydney, NSW 2006, Australia
- School of Physics, University of Sydney, NSW 2006, Australia
- Sydney Nano Institute, University of Sydney, NSW 2006, Australia
| | - Johnny Kuan Un Wong
- Charles Perkins Centre, University of Sydney, NSW 2006, Australia
- School of Life and Environmental Sciences, University of Sydney, NSW 2006, Australia
- Sydney Nano Institute, University of Sydney, NSW 2006, Australia
| | - Katazhyna Redzikultsava
- School of Biomedical Engineering, University of Sydney, NSW 2006, Australia
- School of Physics, University of Sydney, NSW 2006, Australia
| | - Mark Baldry
- School of Biomedical Engineering, University of Sydney, NSW 2006, Australia
- School of Physics, University of Sydney, NSW 2006, Australia
- Sydney Nano Institute, University of Sydney, NSW 2006, Australia
| | - Seyedeh Kh Alavi
- School of Biomedical Engineering, University of Sydney, NSW 2006, Australia
- School of Physics, University of Sydney, NSW 2006, Australia
| | - Ziyu Wang
- Charles Perkins Centre, University of Sydney, NSW 2006, Australia
- School of Life and Environmental Sciences, University of Sydney, NSW 2006, Australia
| | | | - Anthony Weiss
- Charles Perkins Centre, University of Sydney, NSW 2006, Australia
- School of Life and Environmental Sciences, University of Sydney, NSW 2006, Australia
| | - Marcela Bilek
- School of Biomedical Engineering, University of Sydney, NSW 2006, Australia
- School of Physics, University of Sydney, NSW 2006, Australia
- Charles Perkins Centre, University of Sydney, NSW 2006, Australia
- Sydney Nano Institute, University of Sydney, NSW 2006, Australia
| | - Giselle C Yeo
- Charles Perkins Centre, University of Sydney, NSW 2006, Australia
- School of Life and Environmental Sciences, University of Sydney, NSW 2006, Australia
| | - Behnam Akhavan
- School of Biomedical Engineering, University of Sydney, NSW 2006, Australia
- School of Physics, University of Sydney, NSW 2006, Australia
- Sydney Nano Institute, University of Sydney, NSW 2006, Australia
- School of Engineering, University of Newcastle, Callaghan, NSW 2308, Australia
- Hunter Medical Research Institute (HMRI), Precision Medicine Program, New Lambton Heights, NSW, 2305, Australia
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22
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Größbacher G, Bartolf-Kopp M, Gergely C, Bernal PN, Florczak S, de Ruijter M, Rodriguez NG, Groll J, Malda J, Jungst T, Levato R. Volumetric Printing Across Melt Electrowritten Scaffolds Fabricates Multi-Material Living Constructs with Tunable Architecture and Mechanics. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2023; 35:e2300756. [PMID: 37099802 DOI: 10.1002/adma.202300756] [Citation(s) in RCA: 30] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/24/2023] [Revised: 04/17/2023] [Indexed: 06/19/2023]
Abstract
Major challenges in biofabrication revolve around capturing the complex, hierarchical composition of native tissues. However, individual 3D printing techniques have limited capacity to produce composite biomaterials with multi-scale resolution. Volumetric bioprinting recently emerged as a paradigm-shift in biofabrication. This ultrafast, light-based technique sculpts cell-laden hydrogel bioresins into 3D structures in a layerless fashion, providing enhanced design freedom over conventional bioprinting. However, it yields prints with low mechanical stability, since soft, cell-friendly hydrogels are used. Herein, the possibility to converge volumetric bioprinting with melt electrowriting, which excels at patterning microfibers, is shown for the fabrication of tubular hydrogel-based composites with enhanced mechanical behavior. Despite including non-transparent melt electrowritten scaffolds in the volumetric printing process, high-resolution bioprinted structures are successfully achieved. Tensile, burst, and bending mechanical properties of printed tubes are tuned altering the electrowritten mesh design, resulting in complex, multi-material tubular constructs with customizable, anisotropic geometries that better mimic intricate biological tubular structures. As a proof-of-concept, engineered tubular structures are obtained by building trilayered cell-laden vessels, and features (valves, branches, fenestrations) that can be rapidly printed using this hybrid approach. This multi-technology convergence offers a new toolbox for manufacturing hierarchical and mechanically tunable multi-material living structures.
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Affiliation(s)
- Gabriel Größbacher
- Department of Orthopaedics, University Medical Center Utrecht, Utrecht University, Utrecht, 3584 CX, The Netherlands
| | - Michael Bartolf-Kopp
- Department of Functional Materials in Medicine and Dentistry, Institute of Functional Materials and Biofabrication (IFB), KeyLab Polymers for Medicine of the Bavarian Polymer Institute (BPI), University of Würzburg, Pleicherwall 2, 97070, Würzburg, Germany
| | - Csaba Gergely
- Department of Functional Materials in Medicine and Dentistry, Institute of Functional Materials and Biofabrication (IFB), KeyLab Polymers for Medicine of the Bavarian Polymer Institute (BPI), University of Würzburg, Pleicherwall 2, 97070, Würzburg, Germany
| | - Paulina Núñez Bernal
- Department of Orthopaedics, University Medical Center Utrecht, Utrecht University, Utrecht, 3584 CX, The Netherlands
| | - Sammy Florczak
- Department of Orthopaedics, University Medical Center Utrecht, Utrecht University, Utrecht, 3584 CX, The Netherlands
| | - Mylène de Ruijter
- Department of Orthopaedics, University Medical Center Utrecht, Utrecht University, Utrecht, 3584 CX, The Netherlands
| | - Núria Ginés Rodriguez
- Department of Orthopaedics, University Medical Center Utrecht, Utrecht University, Utrecht, 3584 CX, The Netherlands
| | - Jürgen Groll
- Department of Functional Materials in Medicine and Dentistry, Institute of Functional Materials and Biofabrication (IFB), KeyLab Polymers for Medicine of the Bavarian Polymer Institute (BPI), University of Würzburg, Pleicherwall 2, 97070, Würzburg, Germany
| | - Jos Malda
- Department of Orthopaedics, University Medical Center Utrecht, Utrecht University, Utrecht, 3584 CX, The Netherlands
- Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, 3584 CT, The Netherlands
| | - Tomasz Jungst
- Department of Functional Materials in Medicine and Dentistry, Institute of Functional Materials and Biofabrication (IFB), KeyLab Polymers for Medicine of the Bavarian Polymer Institute (BPI), University of Würzburg, Pleicherwall 2, 97070, Würzburg, Germany
| | - Riccardo Levato
- Department of Orthopaedics, University Medical Center Utrecht, Utrecht University, Utrecht, 3584 CX, The Netherlands
- Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, 3584 CT, The Netherlands
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23
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Hu Y, Zhang H, Wang S, Cao L, Zhou F, Jing Y, Su J. Bone/cartilage organoid on-chip: Construction strategy and application. Bioact Mater 2023; 25:29-41. [PMID: 37056252 PMCID: PMC10087111 DOI: 10.1016/j.bioactmat.2023.01.016] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Revised: 01/15/2023] [Accepted: 01/16/2023] [Indexed: 01/21/2023] Open
Abstract
The necessity of disease models for bone/cartilage related disorders is well-recognized, but the barrier between ex-vivo cell culture, animal models and the real human body has been pending for decades. The organoid-on-a-chip technique showed opportunity to revolutionize basic research and drug screening for diseases like osteoporosis and arthritis. The bone/cartilage organoid on-chip (BCoC) system is a novel platform of multi-tissue which faithfully emulate the essential elements, biologic functions and pathophysiological response under real circumstances. In this review, we propose the concept of BCoC platform, summarize the basic modules and current efforts to orchestrate them on a single microfluidic system. Current disease models, unsolved problems and future challenging are also discussed, the aim should be a deeper understanding of diseases, and ultimate realization of generic ex-vivo tools for further therapeutic strategies of pathological conditions.
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24
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Wang Y, Hang K, Ying L, Wu J, Wu X, Zhang W, Li L, Wang Z, Bai J, Gao X, Xue D, Pan Z. LAMP2A regulates the balance of mesenchymal stem cell adipo-osteogenesis via the Wnt/β-catenin/GSK3β signaling pathway. J Mol Med (Berl) 2023; 101:783-799. [PMID: 37162558 DOI: 10.1007/s00109-023-02328-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Revised: 04/24/2023] [Accepted: 04/25/2023] [Indexed: 05/11/2023]
Abstract
Chaperone-mediated autophagy (CMA) plays multiple roles in cell metabolism. We found that lysosome-associated membrane protein type 2A (LAMP2A), a crucial protein of CMA, plays a key role in the control of mesenchymal stem cell (MSC) adipo-osteogenesis. We identified a differentially expressed CMA gene (LAMP2) in GEO datasets (GSE4911 and GSE494). Further, we performed co-expression analyses to define the relationships between CMA components genes and other relevant genes including Col1a1, Runx2, Wnt3 and Gsk3β. Mouse BMSCs (mMSCs) exhibiting Lamp2a gene knockdown (LA-KD) and overexpression (LA-OE) were created using an adenovirus system; then we investigated LAMP2A function in vitro by Western blot, Oil Red staining, ALP staining, ARS staining and Immunofluorescence analysis. Next, we used a modified mouse model of tibial fracture to investigate LAMP2A function in vivo. LAMP2A knockdown in mMSCs decreased the levels of osteogenic-specific proteins (COL1A1 and RUNX2) and increased those of the adipogenesis markers PPARγ and C/EBPα; LAMP2A overexpression had the opposite effects. The active-β-catenin and phospho-GSK3β (Ser9) levels were upregulated by LAMP2A overexpression and downregulated by LAMP2A knockdown. In the mouse model of tibial fracture, mMSC-overexpressing LAMP2A improved bone healing, as demonstrated by microcomputed tomography and histological analyses. In summary, LAMP2A positively regulates mMSC osteogenesis and suppresses adipo-osteogenesis, probably via Wnt/β-catenin/GSK3β signaling. LAMP2A promoted fracture-healing in the mouse model of tibial fracture. KEY MESSAGES: • LAMP2 positively regulates the mBMSCs osteogenic differentiation. • LAMP2 negatively regulates the mBMSCs adipogenic differentiation. • LAMP2 regulates mBMSCs osteogenesis via Wnt/β-catenin/GSK3β signaling pathway. • LAMP2 overexpression mBMSCs promote the fracture healing.
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Affiliation(s)
- Yibo Wang
- Department of Orthopedic Surgery of the Second Affiliated Hospital, School of Medicine, Zhejiang University, No. 88, Jiefang Road, Hangzhou, 310009, China
- Orthopedics Research Institute of Zhejiang University, No. 88, Jiefang Road, Hangzhou, 310009, China
| | - Kai Hang
- Department of Orthopedic Surgery of the Second Affiliated Hospital, School of Medicine, Zhejiang University, No. 88, Jiefang Road, Hangzhou, 310009, China
- Orthopedics Research Institute of Zhejiang University, No. 88, Jiefang Road, Hangzhou, 310009, China
| | - Li Ying
- Department of Orthopedic, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, No. 150, Ximen Street, Linhai, 317000, China
| | - Jiaqi Wu
- Department of Orthopedic Surgery of the Second Affiliated Hospital, School of Medicine, Zhejiang University, No. 88, Jiefang Road, Hangzhou, 310009, China
- Orthopedics Research Institute of Zhejiang University, No. 88, Jiefang Road, Hangzhou, 310009, China
| | - Xiaoyong Wu
- Department of Orthopedic Surgery of the Second Affiliated Hospital, School of Medicine, Zhejiang University, No. 88, Jiefang Road, Hangzhou, 310009, China
- Orthopedics Research Institute of Zhejiang University, No. 88, Jiefang Road, Hangzhou, 310009, China
| | - Weijun Zhang
- Department of Orthopedic Surgery of the Second Affiliated Hospital, School of Medicine, Zhejiang University, No. 88, Jiefang Road, Hangzhou, 310009, China
- Orthopedics Research Institute of Zhejiang University, No. 88, Jiefang Road, Hangzhou, 310009, China
| | - Lijun Li
- Department of Orthopedic Surgery of the Second Affiliated Hospital, School of Medicine, Zhejiang University, No. 88, Jiefang Road, Hangzhou, 310009, China
- Orthopedics Research Institute of Zhejiang University, No. 88, Jiefang Road, Hangzhou, 310009, China
| | - Zhongxiang Wang
- Department of Orthopedic Surgery of the Second Affiliated Hospital, School of Medicine, Zhejiang University, No. 88, Jiefang Road, Hangzhou, 310009, China
- Orthopedics Research Institute of Zhejiang University, No. 88, Jiefang Road, Hangzhou, 310009, China
| | - Jinwu Bai
- Department of Orthopedic Surgery of the Second Affiliated Hospital, School of Medicine, Zhejiang University, No. 88, Jiefang Road, Hangzhou, 310009, China
- Orthopedics Research Institute of Zhejiang University, No. 88, Jiefang Road, Hangzhou, 310009, China
| | - Xiang Gao
- Department of Orthopedic Surgery of the Second Affiliated Hospital, School of Medicine, Zhejiang University, No. 88, Jiefang Road, Hangzhou, 310009, China.
- Orthopedics Research Institute of Zhejiang University, No. 88, Jiefang Road, Hangzhou, 310009, China.
| | - Deting Xue
- Department of Orthopedic Surgery of the Second Affiliated Hospital, School of Medicine, Zhejiang University, No. 88, Jiefang Road, Hangzhou, 310009, China.
- Orthopedics Research Institute of Zhejiang University, No. 88, Jiefang Road, Hangzhou, 310009, China.
| | - Zhijun Pan
- Department of Orthopedic Surgery of the Second Affiliated Hospital, School of Medicine, Zhejiang University, No. 88, Jiefang Road, Hangzhou, 310009, China.
- Orthopedics Research Institute of Zhejiang University, No. 88, Jiefang Road, Hangzhou, 310009, China.
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25
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Ma Z, Guo X, Zhang J, Jiang Q, Liang W, Meng W, Chen S, Zhu Y, Ye C, Jia K. Evaluation of safety and efficacy of the bone marrow mesenchymal stem cell and gelatin-nano-hydroxyapatite combination in canine femoral defect repair. Front Vet Sci 2023; 10:1162407. [PMID: 37415965 PMCID: PMC10320857 DOI: 10.3389/fvets.2023.1162407] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Accepted: 06/06/2023] [Indexed: 07/08/2023] Open
Abstract
Femoral shaft fracture is a common bone trauma in dogs. The limitation of mesenchymal stem cells in bone defect applications is that the cell suspension cannot be fixed to the bone defect site. In the study, our objective was to substantiate the combined application of canine bone marrow mesenchymal stem cells (cBMSCs) and gelatin-nano-hydroxyapatite (Gel-nHAP) and evaluate its therapeutic effect on bone defect diseases in dogs. Experiments were performed to evaluate the following: (1) the porosity of Gel-nHAP; (2) the adhesion of cBMSCs to Gel-nHAP; and (3) the effect of Gel-nHAP on cBMSC proliferation. The efficacy and safety of the combination of cBMSC and Gel-nHAP in the repair of femoral shaft defects were evaluated in animal experiments. The results showed that Gel-nHAP supported the attachment of cBMSCs and exhibited good biocompatibility. In the animal bone defect repair experiment, significant cortical bone growth was observed in the Gel-nHAP group at week 8 (p < 0.05) and in the cBMSCs-Gel-nHAP group at week 4 (p < 0.01). We demonstrated that Gel-nHAP could promote the repair of bone defects, and the effect of cBMSC-Gel-nHAP on the repair of bone defects was profound.
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Affiliation(s)
- Zihang Ma
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
- Guangdong Technological Engineering Research Center for Pet, Guangzhou, China
| | - Xiaoying Guo
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
- Guangdong Technological Engineering Research Center for Pet, Guangzhou, China
| | - Jun Zhang
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
- Guangdong Technological Engineering Research Center for Pet, Guangzhou, China
- Guangdong Polytechnic of Science and Trade, Guangzhou, China
| | - Qifeng Jiang
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
- Guangdong Technological Engineering Research Center for Pet, Guangzhou, China
| | - Wuying Liang
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
- Guangdong Technological Engineering Research Center for Pet, Guangzhou, China
| | - Wenxin Meng
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
- Guangdong Technological Engineering Research Center for Pet, Guangzhou, China
| | - Shuaijiang Chen
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
- Guangdong Technological Engineering Research Center for Pet, Guangzhou, China
| | - Yufan Zhu
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
- Guangdong Technological Engineering Research Center for Pet, Guangzhou, China
| | - Cundong Ye
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
- Guangdong Technological Engineering Research Center for Pet, Guangzhou, China
- College of Tropical Agriculture and Forestry, Guangdong Agriculture Industry Business Polytechnic, Guangzhou, China
| | - Kun Jia
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
- Guangdong Technological Engineering Research Center for Pet, Guangzhou, China
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26
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Pinto-Cardoso R, Bessa-Andrês C, Correia-de-Sá P, Bernardo Noronha-Matos J. Could hypoxia rehabilitate the osteochondral diseased interface? Lessons from the interplay of hypoxia and purinergic signals elsewhere. Biochem Pharmacol 2023:115646. [PMID: 37321413 DOI: 10.1016/j.bcp.2023.115646] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2023] [Revised: 06/03/2023] [Accepted: 06/07/2023] [Indexed: 06/17/2023]
Abstract
The osteochondral unit comprises the articular cartilage (90%), subchondral bone (5%) and calcified cartilage (5%). All cells present at the osteochondral unit that is ultimately responsible for matrix production and osteochondral homeostasis, such as chondrocytes, osteoblasts, osteoclasts and osteocytes, can release adenine and/or uracil nucleotides to the local microenvironment. Nucleotides are released by these cells either constitutively or upon plasma membrane damage, mechanical stress or hypoxia conditions. Once in the extracellular space, endogenously released nucleotides can activate membrane-bound purinoceptors. Activation of these receptors is fine-tuning regulated by nucleotides' breakdown by enzymes of the ecto-nucleotidase cascade. Depending on the pathophysiological conditions, both the avascular cartilage and the subchondral bone subsist to significant changes in oxygen tension, which has a tremendous impact on tissue homeostasis. Cell stress due to hypoxic conditions directly influences the expression and activity of several purinergic signalling players, namely nucleotide release channels (e.g. Cx43), NTPDase enzymes and purinoceptors. This review gathers experimental evidence concerning the interplay between hypoxia and the purinergic signalling cascade contributing to osteochondral unit homeostasis. Reporting deviations to this relationship resulting from pathological alterations of articular joints may ultimately unravel novel therapeutic targets for osteochondral rehabilitation. At this point, one can only hypothesize how hypoxia mimetic conditions can be beneficial to the ex vivo expansion and differentiation of osteo- and chondro-progenitors for auto-transplantation and tissue regenerative purposes.
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Affiliation(s)
- Rui Pinto-Cardoso
- Laboratório de Farmacologia e Neurobiologia; Center for Drug Discovery and Innovative Medicines (MedInUP), Departamento de Imuno-Fisiologia e Farmacologia, Instituto de Ciências Biomédicas Abel Salazar - Universidade do Porto (ICBAS-UP)
| | - Catarina Bessa-Andrês
- Laboratório de Farmacologia e Neurobiologia; Center for Drug Discovery and Innovative Medicines (MedInUP), Departamento de Imuno-Fisiologia e Farmacologia, Instituto de Ciências Biomédicas Abel Salazar - Universidade do Porto (ICBAS-UP)
| | - Paulo Correia-de-Sá
- Laboratório de Farmacologia e Neurobiologia; Center for Drug Discovery and Innovative Medicines (MedInUP), Departamento de Imuno-Fisiologia e Farmacologia, Instituto de Ciências Biomédicas Abel Salazar - Universidade do Porto (ICBAS-UP)
| | - José Bernardo Noronha-Matos
- Laboratório de Farmacologia e Neurobiologia; Center for Drug Discovery and Innovative Medicines (MedInUP), Departamento de Imuno-Fisiologia e Farmacologia, Instituto de Ciências Biomédicas Abel Salazar - Universidade do Porto (ICBAS-UP).
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27
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Administration of stem cells against cardiovascular diseases with a focus on molecular mechanisms: Current knowledge and prospects. Tissue Cell 2023; 81:102030. [PMID: 36709696 DOI: 10.1016/j.tice.2023.102030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2022] [Revised: 01/15/2023] [Accepted: 01/16/2023] [Indexed: 01/20/2023]
Abstract
Cardiovascular diseases (CVDs) are a serious global concern for public and human health. Despite the emergence of significant therapeutic advances, it is still the leading cause of death and disability worldwide. As a result, extensive efforts are underway to develop practical therapeutic approaches. Stem cell-based therapies could be considered a promising strategy for the treatment of CVDs. The efficacy of stem cell-based therapeutic approaches is demonstrated through recent laboratory and clinical studies due to their inherent regenerative properties, proliferative nature, and their capacity to differentiate into different cells such as cardiomyocytes. These properties could improve cardiovascular functioning leading to heart regeneration. The two most common types of stem cells with the potential to cure heart diseases are induced pluripotent stem cells (iPSCs) and mesenchymal stem cells (MSCs). Several studies have demonstrated the use, efficacy, and safety of MSC and iPSCs-based therapies for the treatment of CVDs. In this study, we explain the application of stem cells, especially iPSCs and MSCs, in the treatment of CVDs with a focus on cellular and molecular mechanisms and then discuss the advantages, disadvantages, and perspectives of using this technology in the treatment of these diseases.
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28
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Lee J, Lee H, Jin EJ, Ryu D, Kim GH. 3D bioprinting using a new photo-crosslinking method for muscle tissue restoration. NPJ Regen Med 2023; 8:18. [PMID: 37002225 PMCID: PMC10066283 DOI: 10.1038/s41536-023-00292-5] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2022] [Accepted: 03/17/2023] [Indexed: 04/03/2023] Open
Abstract
Three-dimensional (3D) bioprinting is a highly effective technique for fabricating cell-loaded constructs in tissue engineering. However, the versatility of fabricating precise and complex cell-loaded hydrogels is limited owing to the poor crosslinking ability of cell-containing hydrogels. Herein, we propose an optic-fiber-assisted bioprinting (OAB) process to efficiently crosslink methacrylated hydrogels. By selecting appropriate processing conditions for the photo-crosslinking technique, we fabricated biofunctional cell-laden structures including methacrylated gelatin (Gelma), collagen, and decellularized extracellular matrix. To apply the method to skeletal muscle regeneration, cell-laden Gelma constructs were processed with a functional nozzle having a topographical cue and an OAB process that could induce a uniaxial alignment of C2C12 and human adipose stem cells (hASCs). Significantly higher degrees of cell alignment and myogenic activities in the cell-laden Gelma structure were observed compared with those in the cell construct that was printed using a conventional crosslinking method. Moreover, an in vivo regenerative potential was observed in volumetric muscle defects in a mouse model. The hASC-laden construct significantly induced greater muscle regeneration than the cell construct without topographical cues. Based on the results, the newly designed bioprinting process can prove to be highly effective in fabricating biofunctional cell-laden constructs for various tissue engineering applications.
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Affiliation(s)
- JaeYoon Lee
- Department of Precision Medicine, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea
| | - Hyeongjin Lee
- Department of Precision Medicine, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea
- Department of Biotechnology and Bioinformatics, Korea University, Sejong, Republic of Korea
| | - Eun-Ju Jin
- Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea
| | - Dongryeol Ryu
- Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.
- Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea.
| | - Geun Hyung Kim
- Department of Precision Medicine, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.
- Department of Biophysics, Institute of Quantum Biophysics, Sungkyunkwan University, Suwon, Republic of Korea.
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In Search of the Holy Grail: Stem Cell Therapy as a Novel Treatment of Heart Failure with Preserved Ejection Fraction. Int J Mol Sci 2023; 24:ijms24054903. [PMID: 36902332 PMCID: PMC10003723 DOI: 10.3390/ijms24054903] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Revised: 02/20/2023] [Accepted: 02/25/2023] [Indexed: 03/06/2023] Open
Abstract
Heart failure, a leading cause of hospitalizations and deaths, is a major clinical problem. In recent years, the increasing incidence of heart failure with preserved ejection fraction (HFpEF) has been observed. Despite extensive research, there is no efficient treatment for HFpEF available. However, a growing body of evidence suggests stem cell transplantation, due to its immunomodulatory effect, may decrease fibrosis and improve microcirculation and therefore, could be the first etiology-based therapy of the disease. In this review, we explain the complex pathogenesis of HFpEF, delineate the beneficial effects of stem cells in cardiovascular therapy, and summarize the current knowledge concerning cell therapy in diastolic dysfunction. Furthermore, we identify outstanding knowledge gaps that may indicate directions for future clinical studies.
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Molecular Mechanisms Responsible for Mesenchymal Stem Cell-Based Modulation of Obstructive Sleep Apnea. Int J Mol Sci 2023; 24:ijms24043708. [PMID: 36835120 PMCID: PMC9958695 DOI: 10.3390/ijms24043708] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2022] [Revised: 01/20/2023] [Accepted: 01/26/2023] [Indexed: 02/16/2023] Open
Abstract
Mesenchymal stem cells (MSCs) are adult stem cells that reside in almost all postnatal tissues where, due to the potent regenerative, pro-angiogenic and immunomodulatory properties, regulate tissue homeostasis. Obstructive sleep apnea (OSA) induces oxidative stress, inflammation and ischemia which recruit MSCs from their niches in inflamed and injured tissues. Through the activity of MSC-sourced anti-inflammatory and pro-angiogenic factors, MSCs reduce hypoxia, suppress inflammation, prevent fibrosis and enhance regeneration of damaged cells in OSA-injured tissues. The results obtained in large number of animal studies demonstrated therapeutic efficacy of MSCs in the attenuation of OSA-induced tissue injury and inflammation. Herewith, in this review article, we emphasized molecular mechanisms which are involved in MSC-based neo-vascularization and immunoregulation and we summarized current knowledge about MSC-dependent modulation of OSA-related pathologies.
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Regulatory Mechanism between Ferritin and Mitochondrial Reactive Oxygen Species in Spinal Ligament-Derived Cells from Ossification of Posterior Longitudinal Ligament Patient. Int J Mol Sci 2023; 24:ijms24032872. [PMID: 36769191 PMCID: PMC9917908 DOI: 10.3390/ijms24032872] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Revised: 01/20/2023] [Accepted: 01/31/2023] [Indexed: 02/05/2023] Open
Abstract
Primary spinal ligament-derived cells (SLDCs) from cervical herniated nucleus pulposus tissue (control, Ctrl) and ossification of the posterior longitudinal ligament (OPLL) tissue of surgical patients were analyzed for pathogenesis elucidation. Here, we found that decreased levels of ferritin and increased levels of alkaline phosphatase (ALP), a bone formation marker, provoked osteogenesis in SLDCs in OPLL. SLDCs from the Ctrl and OPLL groups satisfied the definition of mesenchymal stem/stromal cells. RNA sequencing revealed that oxidative phosphorylation and the citric acid cycle pathway were upregulated in the OPLL group. SLDCs in the OPLL group showed increased mitochondrial mass, increased mitochondrial reactive oxygen species (ROS) production, decreased levels of ROS scavengers including ferritin. ROS and ferritin levels were upregulated and downregulated in a time-dependent manner, and both types of molecules repressed ALP. Osteogenesis was mitigated by apoferritin addition. We propose that enhancing ferritin levels might alleviate osteogenesis in OPLL.
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Pagani CA, Bancroft AC, Tower RJ, Livingston N, Sun Y, Hong JY, Kent RN, Strong AL, Nunez JH, Medrano JMR, Patel N, Nanes BA, Dean KM, Li Z, Ge C, Baker BM, James AW, Weiss SJ, Franceschi RT, Levi B. Discoidin domain receptor 2 regulates aberrant mesenchymal lineage cell fate and matrix organization. SCIENCE ADVANCES 2022; 8:eabq6152. [PMID: 36542719 PMCID: PMC9770942 DOI: 10.1126/sciadv.abq6152] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Accepted: 11/05/2022] [Indexed: 06/17/2023]
Abstract
Extracellular matrix (ECM) interactions regulate both the cell transcriptome and proteome, thereby determining cell fate. Traumatic heterotopic ossification (HO) is a disorder characterized by aberrant mesenchymal lineage (MLin) cell differentiation, forming bone within soft tissues of the musculoskeletal system following traumatic injury. Recent work has shown that HO is influenced by ECM-MLin cell receptor signaling, but how ECM binding affects cellular outcomes remains unclear. Using time course transcriptomic and proteomic analyses, we identified discoidin domain receptor 2 (DDR2), a cell surface receptor for fibrillar collagen, as a key MLin cell regulator in HO formation. Inhibition of DDR2 signaling, through either constitutive or conditional Ddr2 deletion or pharmaceutical inhibition, reduced HO formation in mice. Mechanistically, DDR2 perturbation alters focal adhesion orientation and subsequent matrix organization, modulating Focal Adhesion Kinase (FAK) and Yes1 Associated Transcriptional Regulator and WW Domain Containing Transcription Regulator 1 (YAP/TAZ)-mediated MLin cell signaling. Hence, ECM-DDR2 interactions are critical in driving HO and could serve as a previously unknown therapeutic target for treating this disease process.
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Affiliation(s)
- Chase A. Pagani
- Center for Organogenesis and Trauma, Department of Surgery, University of Texas Southwestern, Dallas, TX, USA
| | - Alec C. Bancroft
- Center for Organogenesis and Trauma, Department of Surgery, University of Texas Southwestern, Dallas, TX, USA
| | - Robert J. Tower
- Center for Organogenesis and Trauma, Department of Surgery, University of Texas Southwestern, Dallas, TX, USA
| | - Nicholas Livingston
- Center for Organogenesis and Trauma, Department of Surgery, University of Texas Southwestern, Dallas, TX, USA
| | - Yuxiao Sun
- Center for Organogenesis and Trauma, Department of Surgery, University of Texas Southwestern, Dallas, TX, USA
| | - Jonathan Y. Hong
- Center for Organogenesis and Trauma, Department of Surgery, University of Texas Southwestern, Dallas, TX, USA
| | - Robert N. Kent
- Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA
| | - Amy L. Strong
- Section of Plastic Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI, USA
| | - Johanna H. Nunez
- Center for Organogenesis and Trauma, Department of Surgery, University of Texas Southwestern, Dallas, TX, USA
| | - Jessica Marie R. Medrano
- Center for Organogenesis and Trauma, Department of Surgery, University of Texas Southwestern, Dallas, TX, USA
| | - Nicole Patel
- Section of Plastic Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI, USA
| | - Benjamin A. Nanes
- Department of Dermatology, University of Texas Southwestern, Dallas, TX, USA
- Lydia Hill Department of Bioinformatics, University of Texas Southwestern, Dallas, TX, USA
| | - Kevin M. Dean
- Lydia Hill Department of Bioinformatics, University of Texas Southwestern, Dallas, TX, USA
- Cecil H. and The Ida Green Center for Systems Biology, University of Texas Southwestern, Dallas, TX, USA
| | - Zhao Li
- Department of Pathology, Johns Hopkins University, Baltimore, MD, USA
| | - Chunxi Ge
- School of Dentistry, University of Michigan, Ann Arbor, MI, USA
| | - Brendon M. Baker
- Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA
| | - Aaron W. James
- Department of Pathology, Johns Hopkins University, Baltimore, MD, USA
| | - Stephen J. Weiss
- Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA
| | | | - Benjamin Levi
- Center for Organogenesis and Trauma, Department of Surgery, University of Texas Southwestern, Dallas, TX, USA
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Sadraei F, Ghollasi M, Khakpai F, Halabian R, Jalali Tehrani H. Osteogenic differentiation of pre-conditioned bone marrow mesenchymal stem cells with Nisin on modified poly-L-lactic-acid nanofibers. Regen Ther 2022; 21:263-270. [PMID: 36092506 PMCID: PMC9440272 DOI: 10.1016/j.reth.2022.07.015] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Revised: 06/18/2022] [Accepted: 07/23/2022] [Indexed: 11/16/2022] Open
Affiliation(s)
- Fariba Sadraei
- Cognitive and Neuroscience Research Center (CNRC), Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Marzieh Ghollasi
- Department of Cell and Molecular Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran
| | - Fatemeh Khakpai
- Cognitive and Neuroscience Research Center (CNRC), Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Raheleh Halabian
- Applied Microbiology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
- Corresponding author. Applied Microbiology Research Center, Systems Biology Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran, Postal Code 14359-44711.
| | - Hora Jalali Tehrani
- Department of Developmental Biology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
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Chen W, Wu P, Yu F, Luo G, Qing L, Tang J. HIF-1α Regulates Bone Homeostasis and Angiogenesis, Participating in the Occurrence of Bone Metabolic Diseases. Cells 2022; 11:cells11223552. [PMID: 36428981 PMCID: PMC9688488 DOI: 10.3390/cells11223552] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2022] [Revised: 10/16/2022] [Accepted: 11/07/2022] [Indexed: 11/12/2022] Open
Abstract
In the physiological condition, the skeletal system's bone resorption and formation are in dynamic balance, called bone homeostasis. However, bone homeostasis is destroyed under pathological conditions, leading to the occurrence of bone metabolism diseases. The expression of hypoxia-inducible factor-1α (HIF-1α) is regulated by oxygen concentration. It affects energy metabolism, which plays a vital role in preventing bone metabolic diseases. This review focuses on the HIF-1α pathway and describes in detail the possible mechanism of its involvement in the regulation of bone homeostasis and angiogenesis, as well as the current experimental studies on the use of HIF-1α in the prevention of bone metabolic diseases. HIF-1α/RANKL/Notch1 pathway bidirectionally regulates the differentiation of macrophages into osteoclasts under different conditions. In addition, HIF-1α is also regulated by many factors, including hypoxia, cofactor activity, non-coding RNA, trace elements, etc. As a pivotal pathway for coupling angiogenesis and osteogenesis, HIF-1α has been widely studied in bone metabolic diseases such as bone defect, osteoporosis, osteonecrosis of the femoral head, fracture, and nonunion. The wide application of biomaterials in bone metabolism also provides a reasonable basis for the experimental study of HIF-1α in preventing bone metabolic diseases.
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Kim WJ, Kim GH. A bioprinted complex tissue model for myotendinous junction with biochemical and biophysical cues. Bioeng Transl Med 2022; 7:e10321. [PMID: 36176596 PMCID: PMC9472009 DOI: 10.1002/btm2.10321] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Revised: 03/07/2022] [Accepted: 03/11/2022] [Indexed: 11/07/2022] Open
Abstract
In the musculoskeletal system, the myotendinous junction (MTJ) is optimally designed from the aspect of force transmission generated from a muscle through a tendon onto the bone to induce movement. Although the MTJ is a key complex tissue in force transmission, the realistic fabrication, and formation of complex tissues can be limited. To obtain the MTJ construct, we prepared two bioinks, muscle- and tendon-derived decellularized extracellular matrix (dECM), which can induce myogenic and tenogenic differentiation of human adipose-derived stem cells (hASCs). By using a modified bioprinting process supplemented with a nozzle consisting of a single-core channel and double-sheath channels, we can achieve three different types of MTJ units, composed of muscle, tendon, and interface zones. Our results indicated that the bioprinted dECM-based constructs induced hASCs to myogenic and tenogenic differentiation. In addition, a significantly higher MTJ-associated gene expression was detected at the MTJ interface with a cell-mixing zone than in the other interface models. Based on the results, the bioprinted MTJ model can be a potential platform for understanding the interaction between muscle and tendon cells, and even the bioprinting method can be extensively applied to obtain complex tissues.
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Affiliation(s)
- Won Jin Kim
- Department of Biomechatronic EngineeringCollege of Biotechnology and Bioengineering, Sungkyunkwan University (SKKU)SuwonRepublic of Korea
| | - Geun Hyung Kim
- Department of Biomechatronic EngineeringCollege of Biotechnology and Bioengineering, Sungkyunkwan University (SKKU)SuwonRepublic of Korea
- Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan UniversitySuwonRepublic of Korea
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Maioli M, Rinaldi S, Cruciani S, Necas A, Fontani V, Corda G, Santaniello S, Rinaldi A, Barcessat A, Necasova A, Castagna A, Filipejova Z, Ventura C, Fozza C. Antisenescence effect of REAC biomodulation to counteract the evolution of myelodysplastic syndrome. Physiol Res 2022; 71:539-549. [PMID: 35899943 PMCID: PMC9616590 DOI: 10.33549/physiolres.934903] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Accepted: 07/15/2022] [Indexed: 11/25/2022] Open
Abstract
About 30 percent of patients diagnosed with myelodysplastic syndromes (MDS) progress to acute myeloid leukemia (AML). The senescence of bone marrow?derived mesenchymal stem cells (BMSCs) seems to be one of the determining factors in inducing this drift. Research is continuously looking for new methodologies and technologies that can use bioelectric signals to act on senescence and cell differentiation towards the phenotype of interest. The Radio Electric Asymmetric Conveyer (REAC) technology, aimed at reorganizing the endogenous bioelectric activity, has already shown to be able to determine direct cell reprogramming effects and counteract the senescence mechanisms in stem cells. Aim of the present study was to prove if the anti-senescence results previously obtained in different kind of stem cells with the REAC Tissue optimization - regenerative (TO-RGN) treatment, could also be observed in BMSCs, evaluating cell viability, telomerase activity, p19ARF, P21, P53, and hTERT gene expression. The results show that the REAC TO-RGN treatment may be a useful tool to counteract the BMSCs senescence which can be the basis of AML drift. Nevertheless, further clinical studies on humans are needed to confirm this hypothesis.
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Affiliation(s)
- M Maioli
- Department of Biomedical Sciences, University of Sassari, Sassari, Italy.
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Yao H, Zhang L, Yan S, He Y, Zhu H, Li Y, Wang D, Yang K. Low-intensity pulsed ultrasound/nanomechanical force generators enhance osteogenesis of BMSCs through microfilaments and TRPM7. J Nanobiotechnology 2022; 20:378. [PMID: 35964037 PMCID: PMC9375242 DOI: 10.1186/s12951-022-01587-3] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Accepted: 08/03/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Low-intensity pulsed ultrasound (LIPUS) has been reported to accelerate fracture healing, but the mechanism is unclear and its efficacy needs to be further optimized. Ultrasound in combination with functionalized microbubbles has been shown to induce local shear forces and controllable mechanical stress in cells, amplifying the mechanical effects of LIPUS. Nanoscale lipid bubbles (nanobubbles) have high stability and good biosafety. However, the effect of LIPUS combined with functionalized nanobubbles on osteogenesis has rarely been studied. RESULTS In this study, we report cyclic arginine-glycine-aspartic acid-modified nanobubbles (cRGD-NBs), with a particle size of ~ 500 nm, able to actively target bone marrow mesenchymal stem cells (BMSCs) via integrin receptors. cRGD-NBs can act as nanomechanical force generators on the cell membrane, and further enhance the BMSCs osteogenesis and bone formation promoted by LIPUS. The polymerization of actin microfilaments and the mechanosensitive transient receptor potential melastatin 7 (TRPM7) ion channel play important roles in BMSCs osteogenesis promoted by LIPUS/cRGD-NBs. Moreover, the mutual regulation of TRPM7 and actin microfilaments promote the effect of LIPUS/cRGD-NBs. The extracellular Ca2 + influx, controlled partly by TRPM7, could participated in the effect of LIPUS/cRGD-NBs on BMSCs. CONCLUSIONS The nanomechanical force generators cRGD-NBs could promote osteogenesis of BMSCs and bone formation induced by LIPUS, through regulation TRPM7, actin cytoskeleton, and intracellular calcium oscillations. This study provides new directions for optimizing the efficacy of LIPUS for fracture healing, and a theoretical basis for the further application and development of LIPUS in clinical practice.
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Affiliation(s)
- Huan Yao
- Pediatric Research Institute, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Engineering Research Center of Stem Cell Therapy, Chongqing, 400014, China.,Department of Ultrasound, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Liang Zhang
- Department of Ultrasound, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Shujin Yan
- Department of Ultrasound, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Yiman He
- Department of Ultrasound, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Hui Zhu
- Department of Ultrasound, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Yasha Li
- Pediatric Research Institute, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Engineering Research Center of Stem Cell Therapy, Chongqing, 400014, China
| | - Dong Wang
- Department of Ultrasound, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Ke Yang
- Pediatric Research Institute, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Engineering Research Center of Stem Cell Therapy, Chongqing, 400014, China.
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Rayat Pisheh H, Ansari M, Eslami H. How is mechanobiology involved in bone regenerative medicine? Tissue Cell 2022; 76:101821. [DOI: 10.1016/j.tice.2022.101821] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Revised: 04/27/2022] [Accepted: 05/10/2022] [Indexed: 10/18/2022]
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Agas D, Gabai V, Sufianov AA, Shneider A, Giovanna Sabbieti M. P62/SQSTM1 enhances osteogenesis and attenuates inflammatory signals in bone marrow microenvironment. Gen Comp Endocrinol 2022; 320:114009. [PMID: 35227727 DOI: 10.1016/j.ygcen.2022.114009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Revised: 02/21/2022] [Accepted: 02/23/2022] [Indexed: 11/04/2022]
Abstract
Bone marrow-derived mesenchymal/stromal stem cells (MSCs) became a major focus of research since the anti-inflammatory features and the osteogenic commitment of these cells can prevent the inflamm-aging and various form of osteopenia in humans and animals. We previously showed that p62/SQSTM1 plasmid can prompt release of anti-inflammatory cytokines/chemokines by MSC when injected in adult mice. Furthermore, it can enhance osteoblastogenesis at the expense of adipogenesis and ameliorate bone density and bone remodeling. On the other hand, absence of p62 partially exhausted MSC pool caused expansion of fat cells within bone marrow and pro-inflammatory mediator's accumulation. Given the critical function of p62 as molecular hub of MSC dynamics, here, using MSCs from p62 knockout adult mice, we investigated the effect of this protein on MSC survival and bone-forming molecule cascades. We found that the main osteogenic routes are impaired in absence of p62. In particular, lack of p62 can suppress Smads activation, and Osterix and CREBs expression, thus significantly modifying the schedule of MSCs differentiation. MSCs obtained from p62-/- mice have also demonstrate an amplified NFκB/ Smad1/5/8 colocalization along with NFκB activation in the nucleus, which precludes Smads binding to target promoters. Considering the "teamwork" of TGFβ, PTH and BMP2 on MSC homeostatic behavior, we consider that p62 exerts an essential role as a hub protein. Lastly, ex vivo pulsing p62-deficient MSCs, which then will be administered to a patient as a cell therapy, may be considered as a treatment for bone and bone marrow disorders.
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Affiliation(s)
- Dimitrios Agas
- School of Biosciences and Veterinary Medicine, University of Camerino, Camerino, (MC), Italy.
| | | | - Albert A Sufianov
- Federal Center of Neurosurgery, Tyumen, Russian Federation; Sechenov First Moscow State Medical University, Moscow, Russian Federation
| | - Alexander Shneider
- CureLab Oncology Inc, Dedham, MA, USA; Ariel University, Department of Molecular Biology, Israel; Peter the Great St. Petersburg Polytechnic University, Institute of Biomedical Systems and Biotechnology, Russian Federation
| | - Maria Giovanna Sabbieti
- School of Biosciences and Veterinary Medicine, University of Camerino, Camerino, (MC), Italy.
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Wei Y, Wang B, Jia L, Huang W, Xiang AP, Fang C, Liang X, Li W. Lateral Mesoderm-Derived Mesenchymal Stem Cells With Robust Osteochondrogenic Potential and Hematopoiesis-Supporting Ability. Front Mol Biosci 2022; 9:767536. [PMID: 35573747 PMCID: PMC9095820 DOI: 10.3389/fmolb.2022.767536] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Accepted: 03/14/2022] [Indexed: 11/13/2022] Open
Abstract
Mesenchymal stem cells (MSCs) are among the most promising cell sources for the treatment of various diseases. Nonetheless, the therapeutic efficacy in clinical trials has been inconsistent due to the heterogeneity of MSCs, which may be partially attributed to their undefined developmental origins. The lateral mesoderm is also a developmental source of MSCs that constitute appendicular skeletal elements in the developing vertebrate embryo. However, it is difficult to isolate homogeneous lateral mesoderm (LM)-derived MSCs from bone tissues or bone marrow due to the lack of understanding of their characteristics. Herein, we successfully established an efficient differentiation protocol for the derivation of MSCs with a LM origin from human pluripotent stem cells (hPSCs) under specific conditions. LM-MSCs resembled bone marrow-derived MSCs (BMSCs) with regard to cell surface markers, global gene profiles, and immunoregulatory activity and showed a homeodomain transcription factor (HOX) gene expression pattern typical of skeletal MSCs in long bones. Moreover, we demonstrated that LM-MSCs had an increased osteogenic/chondrogenic differentiation capacity and hematopoietic support potential compared to BMSCs. These homogeneous LM-MSCs may serve as a powerful tool for elucidating their precise role in bone formation and hematopoiesis and could be a potentially ideal cell source for therapeutic applications.
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Affiliation(s)
- Yili Wei
- Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China
| | - Bin Wang
- Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China
| | - Lei Jia
- Reproductive Medicine Research Center, Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Weijun Huang
- Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China
| | - Andy Peng Xiang
- Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China
- Department of Biochemistry, Zhongshan Medical School, Sun Yat-Sen University, Guangzhou, China
| | - Cong Fang
- Reproductive Medicine Research Center, Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Xiaoyan Liang
- Reproductive Medicine Research Center, Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
- *Correspondence: Xiaoyan Liang, ; Weiqiang Li,
| | - Weiqiang Li
- Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China
- Department of Biochemistry, Zhongshan Medical School, Sun Yat-Sen University, Guangzhou, China
- *Correspondence: Xiaoyan Liang, ; Weiqiang Li,
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[Research progress of different cell seeding densities and cell ratios in cartilage tissue engineering]. ZHONGGUO XIU FU CHONG JIAN WAI KE ZA ZHI = ZHONGGUO XIUFU CHONGJIAN WAIKE ZAZHI = CHINESE JOURNAL OF REPARATIVE AND RECONSTRUCTIVE SURGERY 2022; 36:470-478. [PMID: 35426288 PMCID: PMC9011064 DOI: 10.7507/1002-1892.202110091] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
OBJECTIVE To review the research progress of different cell seeding densities and cell ratios in cartilage tissue engineering. METHODS The literature about tissue engineered cartilage constructed with three-dimensional scaffold was extensively reviewed, and the seeding densities and ratios of most commonly used seed cells were summarized. RESULTS Articular chondrocytes (ACHs) and bone marrow mesenchymal stem cells (BMSCs) are the most commonly used seed cells, and they can induce hyaline cartilage formation in vitro and in vivo. Cell seeding density and cell ratio both play important roles in cartilage formation. Tissue engineered cartilage with good quality can be produced when the cell seeding density of ACHs or BMSCs reaches or exceeds that in normal articular cartilage. Under the same culture conditions, the ability of pure BMSCs to build hyaline cartilage is weeker than that of pure ACHs or co-culture of both. CONCLUSION Due to the effect of scaffold materials, growth factors, and cell passages, optimal cell seeding density and cell ratio need further study.
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Ganjian M, Modaresifar K, Rompolas D, Fratila-Apachitei LE, Zadpoor AA. Nanoimprinting for high-throughput replication of geometrically precise pillars in fused silica to regulate cell behavior. Acta Biomater 2022; 140:717-729. [PMID: 34875357 DOI: 10.1016/j.actbio.2021.12.001] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 11/04/2021] [Accepted: 12/01/2021] [Indexed: 12/31/2022]
Abstract
Developing high-throughput nanopatterning techniques that also allow for precise control over the dimensions of the fabricated features is essential for the study of cell-nanopattern interactions. Here, we developed a process that fulfills both of these criteria. Firstly, we used electron-beam lithography (EBL) to fabricate precisely controlled arrays of submicron pillars with varying values of interspacing on a large area of fused silica. Two types of etching procedures with two different systems were developed to etch the fused silica and create the final desired height. We then studied the interactions of preosteoblasts (MC3T3-E1) with these pillars. Varying interspacing was observed to significantly affect the morphological characteristics of the cell, the organization of actin fibers, and the formation of focal adhesions. The expression of osteopontin (OPN) significantly increased on the patterns, indicating the potential of the pillars for inducing osteogenic differentiation. The EBL pillars were thereafter used as master molds in two subsequent processing steps, namely soft lithography and thermal nanoimprint lithography for high-fidelity replication of the pillars on the substrates of interest. The molding parameters were optimized to maximize the fidelity of the generated patterns and minimize the wear and tear of the master mold. Comparing the replicated feature with those present on the original mold confirmed that the geometry and dimensions of the replicated pillars closely resemble those of the original ones. The method proposed in this study, therefore, enables the precise fabrication of submicron- and nanopatterns on a wide variety of materials that are relevant for systematic cell studies. STATEMENT OF SIGNIFICANCE: Submicron pillars with specific dimensions on the bone implants have been proven to be effective in controlling cell behaviors. Nowadays, numerous methods have been proposed to produce bio-instructive submicron-topographies. However, most of these techniques are suffering from being low-throughput, low-precision, and expensive. Here, we developed a high-throughput nanopatterning technique that allows for control over the dimensions of the features for the study of cell-nanotopography interactions. Assessing the adaptation of preosteoblast cells showed the potential of the pillars for inducing osteogenic differentiation. Afterward, the pillars were used for high-fidelity replication of the bio-instructive features on the substrates of interest. The results show the advantages of nanoimprint lithography as a unique technique for the patterning of large areas of bio-instructive surfaces.
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Schumacher M, Habibović P, van Rijt S. Peptide-Modified Nano-Bioactive Glass for Targeted Immobilization of Native VEGF. ACS APPLIED MATERIALS & INTERFACES 2022; 14:4959-4968. [PMID: 35041377 PMCID: PMC8815037 DOI: 10.1021/acsami.1c21378] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/03/2023]
Abstract
A limiting factor in large bone defect regeneration is the slow and disorganized formation of a functional vascular network in the defect area, often resulting in delayed healing or implant failure. To overcome this, strategies that induce angiogenic processes should be combined with potent bone graft substitutes in new bone regeneration approaches. To this end, we describe a unique approach to immobilize the pro-angiogenic growth factor VEGF165 in its native state on the surface of nanosized bioactive glass particles (nBGs) via a binding peptide (PR1P). We demonstrate that covalent coupling of the peptide to amine functional groups grafted on the nBG surface allows immobilization of VEGF with high efficiency and specificity. The amount of coupled peptide could be controlled by varying amine density, which eventually allows tailoring the amount of bound VEGF within a physiologically effective range. In vitro analysis of endothelial cell tube formation in response to VEGF-carrying nBG confirmed that the biological activity of VEGF is not compromised by the immobilization. Instead, comparable angiogenic stimulation was found for lower doses of immobilized VEGF compared to exogenously added VEGF. The described system, for the first time, employs a binding peptide for growth factor immobilization on bioactive glass nanoparticles and represents a promising strategy to overcome the problem of insufficient neovascularization in large bone defect regeneration.
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The horizon of bone organoid: A perspective on construction and application. Bioact Mater 2022; 18:15-25. [PMID: 35387160 PMCID: PMC8961298 DOI: 10.1016/j.bioactmat.2022.01.048] [Citation(s) in RCA: 83] [Impact Index Per Article: 27.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2022] [Revised: 01/29/2022] [Accepted: 01/30/2022] [Indexed: 12/19/2022] Open
Abstract
Bone defects repair and regeneration by various causes such as tumor resection, trauma, degeneration, etc. have always been a key issue in the clinics. As one of the few organs that can regenerate after adulthood, bone itself has a strong regenerative ability. In recent decades, bone tissue engineering technology provides various types of functional scaffold materials and seed cells for bone regeneration and repair, which significantly accelerates the speed and quality of bone regeneration, and many clinical problems are gradually solved. However, the bone metabolism mechanism is complicated, the research duration is long and difficult, which significantly restricts the progress of bone regeneration and repair research. Organoids as a new concept, which is built in vitro with the help of tissue engineering technology based on biological theory, can simulate the complex biological functions of organs in vivo. Once proposed, it shows broad application prospects in the research of organ development, drug screening, mechanism study, and so on. As a complex and special organ, bone organoid construction itself is quite challenging. This review will introduce the characteristics of bone microenvironment, the concept of organoids, focus on the research progress of bone organoids, and propose the strategies for bone organoid construction, study direction, and application prospects.
This review introduces the concept and recent progress of bone organoids. This review proposes the study focus and strategies for constructing bone organoids. This review summarizes the potential applications of bone organoids.
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Tang L, Wu T, Zhou Y, Zhong Y, Sun L, Guo J, Fan X, Ta D. Study on synergistic effects of carboxymethyl cellulose and LIPUS for bone tissue engineering. Carbohydr Polym 2022; 286:119278. [DOI: 10.1016/j.carbpol.2022.119278] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Revised: 01/28/2022] [Accepted: 02/18/2022] [Indexed: 02/07/2023]
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Sun YL, Shang LR, Liu RH, Li XY, Zhang SH, Ren YK, Fu K, Cheng HB, Yahaya BH, Liu YL, Lin JT. Therapeutic effects of menstrual blood-derived endometrial stem cells on mouse models of streptozotocin-induced type 1 diabetes. World J Stem Cells 2022; 14:104-116. [PMID: 35126831 PMCID: PMC8788184 DOI: 10.4252/wjsc.v14.i1.104] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Revised: 07/20/2021] [Accepted: 12/25/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Type 1 diabetes (T1D), a chronic metabolic and autoimmune disease, seriously endangers human health. In recent years, mesenchymal stem cell (MSC) transplantation has become an effective treatment for diabetes. Menstrual blood-derived endometrial stem cells (MenSC), a novel MSC type derived from the decidual endometrium during menstruation, are expected to become promising seeding cells for diabetes treatment because of their noninvasive collection procedure, high proliferation rate and high immunomodulation capacity.
AIM To comprehensively compare the effects of MenSC and umbilical cord-derived MSC (UcMSC) transplantation on T1D treatment, to further explore the potential mechanism of MSC-based therapies in T1D, and to provide support for the clinical application of MSC in diabetes treatment.
METHODS A conventional streptozotocin-induced T1D mouse model was established, and the effects of MenSC and UcMSC transplantation on their blood glucose and serum insulin levels were detected. The morphological and functional changes in the pancreas, liver, kidney, and spleen were analyzed by routine histological and immunohistochemical examinations. Changes in the serum cytokine levels in the model mice were assessed by protein arrays. The expression of target proteins related to pancreatic regeneration and apoptosis was examined by western blot.
RESULTS MenSC and UcMSC transplantation significantly improved the blood glucose and serum insulin levels in T1D model mice. Immunofluorescence analysis revealed that the numbers of insulin+ and CD31+ cells in the pancreas were significantly increased in MSC-treated mice compared with control mice. Subsequent western blot analysis also showed that vascular endothelial growth factor (VEGF), Bcl2, Bcl-xL and Proliferating cell nuclear antigen in pancreatic tissue was significantly upregulated in MSC-treated mice compared with control mice. Additionally, protein arrays indicated that MenSC and UcMSC transplantation significantly downregulated the serum levels of interferon γ and tumor necrosis factor α and upregulated the serum levels of interleukin-6 and VEGF in the model mice. Additionally, histological and immunohistochemical analyses revealed that MSC transplantation systematically improved the morphologies and functions of the liver, kidney, and spleen in T1D model mice.
CONCLUSION MenSC transplantation significantly improves the symptoms in T1D model mice and exerts protective effects on their main organs. Moreover, MSC-mediated angiogenesis, antiapoptotic effects and immunomodulation likely contribute to the above improvements. Thus, MenSC are expected to become promising seeding cells for clinical diabetes treatment due to their advantages mentioned above.
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Affiliation(s)
- Yu-Liang Sun
- Stem Cell and Biotherapy Technology Research Center, Xinxiang Medical University, Xinxiang 453000, Henan Province, China
- Regenerative Medicine Cluster, Advanced Medical and Dental Institute (IPPT), Universiti Sains Malaysia, Kepala Batas 13200, Penang, Malaysia
| | - Ling-Rui Shang
- Stem Cell and Biotherapy Technology Research Center, Xinxiang Medical University, Xinxiang 453000, Henan Province, China
| | - Rui-Hong Liu
- College of Biomedical Engineering, Xinxiang Medical University, Xinxiang 453000, Henan Province, China
| | - Xin-Yi Li
- Stem Cell and Biotherapy Technology Research Center, Xinxiang Medical University, Xinxiang 453000, Henan Province, China
| | - Sheng-Hui Zhang
- The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang Medical University, Xinxiang 453000, Henan Province, China
| | - Ya-Kun Ren
- Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang 453000, Henan Province, China
| | - Kang Fu
- Department of Technical, Henan Intercell Biotechnology co. LTD, Xinxiang 453000, Henan Province, China
| | - Hong-Bin Cheng
- College of Biomedical Engineering, Xinxiang Medical University, Xinxiang 453000, Henan Province, China
| | - Badrul Hisham Yahaya
- Regenerative Medicine Cluster, Advanced Medical and Dental Institute (IPPT), Universiti Sains Malaysia, Kepala Batas 13200, Penang, Malaysia
| | - Yan-Li Liu
- Stem Cell and Biotherapy Technology Research Center, Xinxiang Medical University, Xinxiang 453000, Henan Province, China
| | - Jun-Tang Lin
- Stem Cell and Biotherapy Technology Research Center, Xinxiang Medical University, Xinxiang 453000, Henan Province, China
- College of Biomedical Engineering, Xinxiang Medical University, Xinxiang 453000, Henan Province, China
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De la Fuente-Hernandez MA, Sarabia-Sanchez MA, Melendez-Zajgla J, Maldonado-Lagunas V. Role of lncRNAs into Mesenchymal Stromal Cell Differentiation. Am J Physiol Cell Physiol 2022; 322:C421-C460. [PMID: 35080923 DOI: 10.1152/ajpcell.00364.2021] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Currently, findings support that 75% of the human genome is actively transcribed, but only 2% is translated into a protein, according to databases such as ENCODE (Encyclopedia of DNA Elements) [1]. The development of high-throughput sequencing technologies, computational methods for genome assembly and biological models have led to the realization of the importance of the previously unconsidered non-coding fraction of the genome. Along with this, noncoding RNAs have been shown to be epigenetic, transcriptional and post-transcriptional regulators in a large number of cellular processes [2]. Within the group of non-coding RNAs, lncRNAs represent a fascinating field of study, given the functional versatility in their mode of action on their molecular targets. In recent years, there has been an interest in learning about lncRNAs in MSC differentiation. The aim of this review is to address the signaling mechanisms where lncRNAs are involved, emphasizing their role in either stimulating or inhibiting the transition to differentiated cell. Specifically, the main types of MSC differentiation are discussed: myogenesis, osteogenesis, adipogenesis and chondrogenesis. The description of increasingly new lncRNAs reinforces their role as players in the well-studied field of MSC differentiation, allowing a step towards a better understanding of their biology and their potential application in the clinic.
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Affiliation(s)
- Marcela Angelica De la Fuente-Hernandez
- Facultad de Medicina, Posgrado en Ciencias Biológicas, Universidad Nacional Autónoma de México, Mexico City, Mexico.,Laboratorio de Epigenética, Instituto Nacional de Medicina Genómica, Mexico City, Mexico
| | - Miguel Angel Sarabia-Sanchez
- Facultad de Medicina, Posgrado en Ciencias Bioquímicas, Universidad Nacional Autónoma de México, Mexico City, Mexico
| | - Jorge Melendez-Zajgla
- Laboratorio de Genómica Funcional del Cáncer, Instituto Nacional de Medicina Genómica, Mexico City, Mexico
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Wang C, Ning H, Gao J, Xue T, Zhao M, Jiang X, Zhu X, Guo X, Li H, Wang X. Disruption of hematopoiesis attenuates the osteogenic differentiation capacity of bone marrow stromal cells. Stem Cell Res Ther 2022; 13:27. [PMID: 35073981 PMCID: PMC8785551 DOI: 10.1186/s13287-022-02708-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Accepted: 10/07/2021] [Indexed: 12/18/2022] Open
Abstract
Background The homeostasis of mesenchymal stem cells (MSCs) is modulated by both their own intracellular molecules and extracellular milieu signals. Hematopoiesis in the bone marrow is maintained by niche cells, including MSCs, and it is indispensable for life. The role of MSCs in maintaining hematopoietic homeostasis has been fully elucidated. However, little is known about the mechanism by which hematopoietic cells reciprocally regulate niche cells. The present study aimed to explore the close relationship between MSCs and hematopoietic cells, which may be exploited for the development of new therapeutic strategies for related diseases. Methods In this study, we isolated cells from the offspring of Tie2Cre + and Ptenflox/flox mice. After cell isolation and culture, we investigated the effect of hematopoietic cells on MSCs using various methods, including flow cytometry, adipogenic and osteogenic differentiation analyses, quantitative PCR, western bloting, and microCT analysis. Results Our results showed that when the phosphatase and tensin homolog deleted on chromosome 10 (Pten) gene was half-deleted in hematopoietic cells, hematopoiesis and osteogenesis were normal in young mice; the frequency of erythroid progenitor cells in the bone marrow gradually decreased and osteogenesis in the femoral epiphysis weakened as the mice grew. The heterozygous loss of Pten in hematopoietic cells leads to the attenuation of osteogenic differentiation and enhanced adipogenic differentiation of MSCs in vitro. Co-culture with normal hematopoietic cells rescued the abnormal differentiation of MSCs, and in contrast, MSCs co-cultured with heterozygous null Pten hematopoietic cells showed abnormal differentiation activity. Co-culture with erythroid progenitor cells also revealed them to play an important role in MSC differentiation. Conclusion Our data suggest that hematopoietic cells function as niche cells of MSCs to balance the differentiation activity of MSCs and may ultimately affect bone development.
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Affiliation(s)
- Changzhen Wang
- The Brain Science Center, Beijing Institute of Basic Medical Sciences, Beijing, 100850, China. .,Laboratory of Bioelectromagnetics, Beijing Institute of Radiation and Medicine, 27 Taiping Road, Haidian District, Beijing, 100850, China.
| | - Hongmei Ning
- Department of Hematology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100071, China
| | - Jiao Gao
- The Chinese People's Liberation Army Strategic Support Force Characteristic Medical Center, Beijing, 100101, China
| | - Teng Xue
- Laboratory of Bioelectromagnetics, Beijing Institute of Radiation and Medicine, 27 Taiping Road, Haidian District, Beijing, 100850, China
| | - Ming Zhao
- The Brain Science Center, Beijing Institute of Basic Medical Sciences, Beijing, 100850, China
| | - Xiaoxia Jiang
- The Brain Science Center, Beijing Institute of Basic Medical Sciences, Beijing, 100850, China
| | - Xiaoming Zhu
- The Brain Science Center, Beijing Institute of Basic Medical Sciences, Beijing, 100850, China
| | - Ximin Guo
- The Brain Science Center, Beijing Institute of Basic Medical Sciences, Beijing, 100850, China
| | - Hong Li
- The Brain Science Center, Beijing Institute of Basic Medical Sciences, Beijing, 100850, China
| | - Xiaoyan Wang
- The Brain Science Center, Beijing Institute of Basic Medical Sciences, Beijing, 100850, China.
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Gao Q, Wang L, Wang S, Huang B, Jing Y, Su J. Bone Marrow Mesenchymal Stromal Cells: Identification, Classification, and Differentiation. Front Cell Dev Biol 2022; 9:787118. [PMID: 35047499 PMCID: PMC8762234 DOI: 10.3389/fcell.2021.787118] [Citation(s) in RCA: 68] [Impact Index Per Article: 22.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Accepted: 11/25/2021] [Indexed: 12/20/2022] Open
Abstract
Bone marrow mesenchymal stromal cells (BMSCs), identified as pericytes comprising the hematopoietic niche, are a group of heterogeneous cells composed of multipotent stem cells, including osteochondral and adipocyte progenitors. Nevertheless, the identification and classification are still controversial, which limits their application. In recent years, by lineage tracing and single-cell sequencing, several new subgroups of BMSCs and their roles in normal physiological and pathological conditions have been clarified. Key regulators and mechanisms controlling the fate of BMSCs are being revealed. Cross-talk among subgroups of bone marrow mesenchymal cells has been demonstrated. In this review, we focus on recent advances in the identification and classification of BMSCs, which provides important implications for clinical applications.
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Affiliation(s)
- Qianmin Gao
- Institute of Translational Medicine, Shanghai University, Shanghai, China.,School of Medicine, Shanghai University, Shanghai, China.,School of Life Sciences, Shanghai University, Shanghai, China.,Shanghai University Institute of Advanced Interdisciplinary Materials Science, Shanghai, China
| | - Lipeng Wang
- Institute of Translational Medicine, Shanghai University, Shanghai, China
| | - Sicheng Wang
- Department of Orthopedics, Shanghai Zhongye Hospital, Shanghai, China
| | - Biaotong Huang
- Institute of Translational Medicine, Shanghai University, Shanghai, China.,Shanghai University Institute of Advanced Interdisciplinary Materials Science, Shanghai, China.,Wenzhou Institute of Shanghai University, Wenzhou, China
| | - Yingying Jing
- Institute of Translational Medicine, Shanghai University, Shanghai, China.,Shanghai University Institute of Advanced Interdisciplinary Materials Science, Shanghai, China
| | - Jiacan Su
- Department of Orthopedics Trauma, Shanghai Changhai Hospital, Naval Medical University, Shanghai, China
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Joint-on-chip platforms: entering a new era of in vitro models for arthritis. Nat Rev Rheumatol 2022; 18:217-231. [PMID: 35058618 DOI: 10.1038/s41584-021-00736-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/08/2021] [Indexed: 12/12/2022]
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