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Haider KH. Priming mesenchymal stem cells to develop "super stem cells". World J Stem Cells 2024; 16:623-640. [PMID: 38948094 PMCID: PMC11212549 DOI: 10.4252/wjsc.v16.i6.623] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Revised: 05/04/2024] [Accepted: 05/20/2024] [Indexed: 06/25/2024] Open
Abstract
The stem cell pre-treatment approaches at cellular and sub-cellular levels encompass physical manipulation of stem cells to growth factor treatment, genetic manipulation, and chemical and pharmacological treatment, each strategy having advantages and limitations. Most of these pre-treatment protocols are non-combinative. This editorial is a continuum of Li et al's published article and Wan et al's editorial focusing on the significance of pre-treatment strategies to enhance their stemness, immunoregulatory, and immunosuppressive properties. They have elaborated on the intricacies of the combinative pre-treatment protocol using pro-inflammatory cytokines and hypoxia. Applying a well-defined multi-pronged combinatorial strategy of mesenchymal stem cells (MSCs), pre-treatment based on the mechanistic understanding is expected to develop "Super MSCs", which will create a transformative shift in MSC-based therapies in clinical settings, potentially revolutionizing the field. Once optimized, the standardized protocols may be used with slight modifications to pre-treat different stem cells to develop "super stem cells" with augmented stemness, functionality, and reparability for diverse clinical applications with better outcomes.
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Affiliation(s)
- Khawaja Husnain Haider
- Department of Basic Sciences, Sulaiman AlRajhi University, AlQaseem 52736, Saudi Arabia.
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Hu X, Su Y, Xu J, Cheng YY, Liu T, Li X, Ma X, Chen Z, Song K. Electromagnetic field-mediated chitosan/gelatin/nano-hydroxyapatite and bone-derived scaffolds regulate the osteoblastic and chondrogenic phenotypes of adipose-derived stem cells to construct osteochondral tissue engineering niche in vitro. Int J Biol Macromol 2024; 258:128829. [PMID: 38128807 DOI: 10.1016/j.ijbiomac.2023.128829] [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: 10/01/2023] [Revised: 11/17/2023] [Accepted: 12/13/2023] [Indexed: 12/23/2023]
Abstract
It is critical to explore the effects of electromagnetic field (EMF) on the construction of functional osteochondral tissue, which has shown certain clinical significance for the treatment of osteochondral injury. At present, there are few studies on the effect of the direction of EMF on cells. This study aimed to investigate the effects of EMF coupling on different parameters to control adipose-derived stem cells (ADSCs) proliferation and specific chondrogenic and osteogenic differentiation at 2D level and 3D level. The proliferation and differentiation of EMF-induced ADSCs are jointly regulated by EMF and space structure. In this study, Cs7/Gel3/nHAP scaffolds were prepared with good degradation rate (86.75 ± 4.96 %) and absorb water (1100 %), and the pore size was 195.63 ± 54.72 μm. The bone-derived scaffold with a pore size of 267.17 ± 129.18 μm was obtained and its main component was hydroxyapatite. Cs7/Gel3/nHAP scaffolds and bone-derived scaffolds are suitable as 3D level materials. The optimal EMF intensity was 2 mT for chondrogenic differentiation and proliferation and 1 mT for osteogenic differentiation and proliferation. It is noteworthy that EMF has a negative correlation with ADSCs proliferation in the vertical direction at 2D level, while it has a positive correlation with ADSCs proliferation at 3D level. EMF mediated 3D osteochondral scaffold provide good strategy for osteochondral tissue engineering construction.
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Affiliation(s)
- Xueyan Hu
- State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024, China
| | - Ya Su
- State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024, China
| | - Jie Xu
- State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024, China
| | - Yuen Yee Cheng
- Institute for Biomedical Materials and Devices, Faculty of Science, University of Technology Sydney, NSW 2007, Australia
| | - Tianqing Liu
- State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024, China
| | - Xiangqin Li
- State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024, China.
| | - Xiao Ma
- Department of Anesthesia, First Affiliated Hospital of Dalian Medical University, Dalian 116011, China.
| | - Zhen Chen
- Clinical Laboratory, First Affiliated Hospital of Dalian Medical University, Dalian 116011, China.
| | - Kedong Song
- State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024, China.
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Yang J, Feng Y, Li Q, Zeng Y. Evidence of the static magnetic field effects on bone-related diseases and bone cells. PROGRESS IN BIOPHYSICS AND MOLECULAR BIOLOGY 2023; 177:168-180. [PMID: 36462638 DOI: 10.1016/j.pbiomolbio.2022.11.006] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Revised: 11/28/2022] [Accepted: 11/30/2022] [Indexed: 12/03/2022]
Abstract
Static magnetic fields (SMFs), magnetic fields with constant intensity and orientation, have been extensively studied in the field of bone biology both fundamentally and clinically as a non-invasive physical factor. A large number of animal experiments and clinical studies have shown that SMFs have effective therapeutic effects on bone-related diseases such as non-healing fractures, bone non-union of bone implants, osteoporosis and osteoarthritis. The maintenance of bone health in adults depends on the basic functions of bone cells, such as bone formation by osteoblasts and bone resorption by osteoclasts. Numerous studies have revealed that SMFs can regulate the proliferation, differentiation, and function of bone tissue cells, including bone marrow mesenchymal stem cells (BMSCs), osteoblasts, bone marrow monocytes (BMMs), osteoclasts, and osteocytes. In this paper, the effects of SMFs on bone-related diseases and bone tissue cells are reviewed from both in vivo studies and in vitro studies, and the possible mechanisms are analyzed. In addition, some challenges that need to be further addressed in the research of SMF and bone are also discussed.
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Affiliation(s)
- Jiancheng Yang
- Department of Osteoporosis, Honghui Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Yan Feng
- Department of Osteoporosis, Honghui Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Qingmei Li
- Department of Osteoporosis, Honghui Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Yuhong Zeng
- Department of Osteoporosis, Honghui Hospital, Xi'an Jiaotong University, Xi'an, China.
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Yang J, Wu J, Guo Z, Zhang G, Zhang H. Iron Oxide Nanoparticles Combined with Static Magnetic Fields in Bone Remodeling. Cells 2022; 11:cells11203298. [PMID: 36291164 PMCID: PMC9600888 DOI: 10.3390/cells11203298] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Accepted: 10/18/2022] [Indexed: 11/27/2022] Open
Abstract
Iron oxide nanoparticles (IONPs) are extensively used in bone-related studies as biomaterials due to their unique magnetic properties and good biocompatibility. Through endocytosis, IONPs enter the cell where they promote osteogenic differentiation and inhibit osteoclastogenesis. Static magnetic fields (SMFs) were also found to enhance osteoblast differentiation and hinder osteoclastic differentiation. Once IONPs are exposed to an SMF, they become rapidly magnetized. IONPs and SMFs work together to synergistically enhance the effectiveness of their individual effects on the differentiation and function of osteoblasts and osteoclasts. This article reviewed the individual and combined effects of different types of IONPs and different intensities of SMFs on bone remodeling. We also discussed the mechanism underlying the synergistic effects of IONPs and SMFs on bone remodeling.
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Affiliation(s)
- Jiancheng Yang
- Department of Spine Surgery, People’s Hospital of Longhua, Affiliated Hospital of Southern Medical University, Shenzhen 518109, China
- Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi’an 710072, China
| | - Jiawen Wu
- Department of Spine Surgery, People’s Hospital of Longhua, Affiliated Hospital of Southern Medical University, Shenzhen 518109, China
| | - Zengfeng Guo
- Department of Spine Surgery, People’s Hospital of Longhua, Affiliated Hospital of Southern Medical University, Shenzhen 518109, China
| | - Gejing Zhang
- Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi’an 710072, China
| | - Hao Zhang
- Department of Spine Surgery, People’s Hospital of Longhua, Affiliated Hospital of Southern Medical University, Shenzhen 518109, China
- Correspondence: ; Tel.: +86-13823352822
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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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Filippi M, Garello F, Yasa O, Kasamkattil J, Scherberich A, Katzschmann RK. Engineered Magnetic Nanocomposites to Modulate Cellular Function. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2022; 18:e2104079. [PMID: 34741417 DOI: 10.1002/smll.202104079] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Revised: 09/13/2021] [Indexed: 06/13/2023]
Abstract
Magnetic nanoparticles (MNPs) have various applications in biomedicine, including imaging, drug delivery and release, genetic modification, cell guidance, and patterning. By combining MNPs with polymers, magnetic nanocomposites (MNCs) with diverse morphologies (core-shell particles, matrix-dispersed particles, microspheres, etc.) can be generated. These MNCs retain the ability of MNPs to be controlled remotely using external magnetic fields. While the effects of these biomaterials on the cell biology are still poorly understood, such information can help the biophysical modulation of various cellular functions, including proliferation, adhesion, and differentiation. After recalling the basic properties of MNPs and polymers, and describing their coassembly into nanocomposites, this review focuses on how polymeric MNCs can be used in several ways to affect cell behavior. A special emphasis is given to 3D cell culture models and transplantable grafts, which are used for regenerative medicine, underlining the impact of MNCs in regulating stem cell differentiation and engineering living tissues. Recent advances in the use of MNCs for tissue regeneration are critically discussed, particularly with regard to their prospective involvement in human therapy and in the construction of advanced functional materials such as magnetically operated biomedical robots.
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Affiliation(s)
- Miriam Filippi
- Soft Robotics Laboratory, ETH Zurich, Tannenstrasse 3, Zurich, 8092, Switzerland
| | - Francesca Garello
- Department of Molecular Biotechnology and Health Sciences, University of Torino, Via Nizza 52, Torino, 10126, Italy
| | - Oncay Yasa
- Soft Robotics Laboratory, ETH Zurich, Tannenstrasse 3, Zurich, 8092, Switzerland
| | - Jesil Kasamkattil
- Department of Biomedicine, University Hospital Basel, Hebelstrasse 20, Basel, 4031, Switzerland
| | - Arnaud Scherberich
- Department of Biomedicine, University Hospital Basel, Hebelstrasse 20, Basel, 4031, Switzerland
- Department of Biomedical Engineering, University of Basel, Gewerbestrasse 14, Allschwil, 4123, Switzerland
| | - Robert K Katzschmann
- Soft Robotics Laboratory, ETH Zurich, Tannenstrasse 3, Zurich, 8092, Switzerland
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Cheng CC, Chung CA, Chang CJ, Cheng YC, Huang CJ, Chien CC, Lin HT. Hydrostatic pressure facilitates calcium deposition and osteogenic gene expression in the osteoblastic differentiation of placenta-derived multipotent cells. Taiwan J Obstet Gynecol 2022; 61:270-276. [PMID: 35361387 DOI: 10.1016/j.tjog.2022.02.014] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/22/2021] [Indexed: 11/19/2022] Open
Abstract
OBJECTIVE We tested the osteoblastic differentiation effects caused by physical stimulation such as hydrostatic pressure using placenta-derived multipotent cells. MATERIALS AND METHODS The placenta-derived multipotent cells (PDMCs) were treated with osteogenic medium to induce PDMCs differentiation into osteoblast-like cells. The induced PDMCs were stimulated using hydrostatic pressure at a magnitude of 30 kPa for 1 h/day for up to 12 days. The calcium deposition monitored by Alizarin Red staining and the calcium content of each experimental group were quantified. RESULTS The results demonstrated both the calcium deposition and concentration were elevated through hydrostatic pressure stimulation. Moreover, in order to indicate of PDMC osteodifferentiation, RT-qPCR analysis were performed and mRNA expression of osteoblast differentiation markers (type I collagen, alkaline phosphatase, RUNX2, and BGLAP), the bone morphogenetic protein family (BMP1-7) and BMP receptors (BMPR1A, BMPR1B, and BMPR2) were examined. Among them, the mRNA levels of RUNX2, COL1A1, BMP1, BMP3, and BMPR1A increased significantly in the hydrostatic-pressure-stimulated groups, whereas BGLAP, ALP, BMP2, BMP6, BMPR1B, and BMPR2 exhibited a slight upregulation between the control and experimental groups, indicating the specific signal route induced by hydrostatic pressure on PDMCs. CONCLUSION Our results revealed the beneficial effects of stem cells stimulated using hydrostatic pressure, which could enhance calcium deposition considerably and facilitate osteodifferentiation, and the results may be applied to tissue regeneration in the near future.
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Affiliation(s)
- Chih-Chien Cheng
- Department of Mechanical Engineering, National Central University, Jhongli, Taiwan; Department of Obstetrics/Gynecology, Taipei City Hospital, Taipei, Taiwan; School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei, Taiwan
| | - Chih-Ang Chung
- Department of Mechanical Engineering, National Central University, Jhongli, Taiwan
| | - Chih-Ju Chang
- Department of Mechanical Engineering, National Central University, Jhongli, Taiwan; School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei, Taiwan; Department of Neurosurgery, Cathay General Hospital, Taipei, Taiwan
| | - Yu-Che Cheng
- School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei, Taiwan; Department of Medical Research, Cathay General Hospital, Taipei, Taiwan; Department of Biomedical Science and Engineering, National Central University, Jhongli, Taiwan
| | - Chi-Jung Huang
- School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei, Taiwan; Department of Medical Research, Cathay General Hospital, Taipei, Taiwan; Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan
| | - Chih-Cheng Chien
- School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei, Taiwan; Department of Medical Research, Cathay General Hospital, Taipei, Taiwan; Department of Anesthesiology, Sijhih Cathay General Hospital, Sijhih District, New Taipei City, Taiwan
| | - Hsi-Ting Lin
- Department of Surgery, Cathay General Hospital, Taipei, Taiwan; Department of Orthopedics, Cathay General Hospital, Taipei, Taiwan.
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Lin S, Li J, Shao J, Zhang J, He X, Huang D, Dong L, Lin J, Weng W, Cheng K. Anisotropic magneto-mechanical stimulation on collagen coatings to accelerate osteogenesis. Colloids Surf B Biointerfaces 2021; 210:112227. [PMID: 34838419 DOI: 10.1016/j.colsurfb.2021.112227] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2021] [Revised: 11/08/2021] [Accepted: 11/14/2021] [Indexed: 01/08/2023]
Abstract
Mechanical stimulation has been considered to be critical to cellular response and tissue regeneration. However, harnessing the direction of mechanical stimulation during osteogenesis still remains a challenge. In this study, we designed a series of novel magnetized collagen coatings (MCCs) (randomly or parallel-oriented collagen fibers) to exert the anisotropic mechanical stimulation using oriented magnetic actuation during osteogenesis. Strikingly, we found the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) were significantly up-regulated when the direction of magnetic actuation was parallel to the randomly-oriented collagen coating surface, in contrast to the down-regulated capacity under the perpendicular magnetic actuation. Moreover, further exerting a parallel mechanical stimulation along the parallel-oriented collagen coating, which cells have been oriented by the oriented collagens, were not only able to up-regulate the osteogenic differentiation of BMSCs but also promote the new bone formation during osteogenesis in vivo. We also demonstrated the anisotropic magneto-mechanical stimulation for the osteogenic differences might be attributed to the stretching or bending tensile status of collagen fibers controlled by the direction of magnetic actuation, driving the α5β1-dependent integrin signaling cascade. This study therefore got insight of understanding the directional mechanical stimulation on osteogenesis, and also paved a way for sustaining regulation of the biomaterials-host interface.
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Affiliation(s)
- Suya Lin
- School of Materials Science and Engineering, State Key Laboratory of Silicon Materials, Center of Rehabilitation Biomedical Materials, Cyrus Tang Center for Sensor Materials and Applications, Zhejiang University, Hangzhou 310027, China
| | - Juan Li
- The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Jiaqi Shao
- The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Jiamin Zhang
- School of Materials Science and Engineering, State Key Laboratory of Silicon Materials, Center of Rehabilitation Biomedical Materials, Cyrus Tang Center for Sensor Materials and Applications, Zhejiang University, Hangzhou 310027, China
| | - Xuzhao He
- School of Materials Science and Engineering, State Key Laboratory of Silicon Materials, Center of Rehabilitation Biomedical Materials, Cyrus Tang Center for Sensor Materials and Applications, Zhejiang University, Hangzhou 310027, China
| | - Donghua Huang
- Department of Orthopaedic Surgery, the Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, China
| | - Lingqing Dong
- The Affiliated Stomatologic Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Jun Lin
- The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.
| | - Wenjian Weng
- School of Materials Science and Engineering, State Key Laboratory of Silicon Materials, Center of Rehabilitation Biomedical Materials, Cyrus Tang Center for Sensor Materials and Applications, Zhejiang University, Hangzhou 310027, China
| | - Kui Cheng
- School of Materials Science and Engineering, State Key Laboratory of Silicon Materials, Center of Rehabilitation Biomedical Materials, Cyrus Tang Center for Sensor Materials and Applications, Zhejiang University, Hangzhou 310027, China; Department of Rehabilitation Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
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Xie F, Wen G, Sun W, Jiang K, Chen T, Chen S, Wen J. Mechanical stress promotes angiogenesis through fibroblast exosomes. Biochem Biophys Res Commun 2020; 533:346-353. [PMID: 32962863 DOI: 10.1016/j.bbrc.2020.04.159] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2020] [Accepted: 04/30/2020] [Indexed: 12/22/2022]
Abstract
BACKGROUND Mechanical stress can induce multiple functional changes in vascular endothelial cells, including proliferation, differentiation, and migration. Furthermore, human fibroblasts are susceptible to external mechanical stress. In this work, we investigated whether mechanical stress can induce exosome secretion from fibroblasts to modulate angiogenesis. METHODS A CCK-8 cell proliferation assay was used to determine mechanical parameters. Then, exosomes from fibroblasts were isolated and characterized with regard to concentration and markers. We subsequently explored the effect of exosomes on proliferation, migration, and angiogenesis. Additionally, high-throughput sequencing was used to screen differentially expressed miRNAs in the mechanical stress-induced exosomes. RESULTS A static stretching of 15% significantly enhanced the cell viability of the fibroblasts (p < 0.05) and significantly induced the secretion of exosomes from the fibroblasts, which had a stronger internalization ability. Further experiments demonstrated that the presence of static stretching-induced exosomes significantly increased cell proliferation, migration, and angiogenesis by regulating the Erk1/2 signaling pathway. Additionally, 12 up-regulated and 12 down-regulated candidate miRNAs were discriminated in the static stretching-induced exosomes. CONCLUSION Our findings conclusively demonstrate that static stretching-derived exosomes from fibroblasts promote angiogenesis through differentially expressed miRNAs, providing novel insights into the molecular mechanism by which mechanical stress influences angiogenesis.
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Affiliation(s)
- Fei Xie
- China Academy of Chinese Medical Sciences, Wangjing Hospital, Beijing, China.
| | - Guannan Wen
- China Academy of Chinese Medical Sciences, Wangjing Hospital, Beijing, China.
| | - Weidong Sun
- China Academy of Chinese Medical Sciences, Wangjing Hospital, Beijing, China.
| | - Kewei Jiang
- China Academy of Chinese Medical Sciences, Wangjing Hospital, Beijing, China.
| | - Ting Chen
- China Academy of Chinese Medical Sciences, Wangjing Hospital, Beijing, China.
| | - Si Chen
- China Academy of Chinese Medical Sciences, Wangjing Hospital, Beijing, China.
| | - Jianmin Wen
- China Academy of Chinese Medical Sciences, Wangjing Hospital, Beijing, China.
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10
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Kämmerer PW, Pabst AM, Dau M, Staedt H, Al-Nawas B, Heller M. Immobilization of BMP-2, BMP-7 and alendronic acid on titanium surfaces: Adhesion, proliferation and differentiation of bone marrow-derived stem cells. J Biomed Mater Res A 2019; 108:212-220. [PMID: 31587476 DOI: 10.1002/jbm.a.36805] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2018] [Revised: 08/28/2019] [Accepted: 09/03/2019] [Indexed: 12/11/2022]
Abstract
This study analyzed the influence of titanium (TiO2 ) surface modifications with two osteogenic proteins (BMP-2, BMP-7) and an anti-osteoclastic drug (alendronic acid [AA]) on sandblasted/acid-etched (SLA) and plain TiO2 (PT) on cell adhesion, proliferation and differentiation (alkaline phosphatase [AP] and osteocalcin [OC]) of bone-marrow derived stem cells (BMSCs) after 1, 3 and 7 days in-vitro. Initially, AA surfaces showed the highest cell number and surface coverage. At day 3 and 7, BMP and AA-modified surfaces exhibited a significantly enhanced cell growth. For proliferation, at days 3 and 7, an enhancement on BMP-2, BMP-7 and AA-surfaces was seen. At day 7, SLA also showed a higher proliferation when compared to PT. Initially, AP expression was elevated on SLA and AA surfaces. At days 3 and 7, a significant increased AP expression was seen for SLA, BMP-2, BMP-7 and AA discs. For OC, SLA and AA surfaces had the highest expression after 1 day whereas after 3 and 7 days a significant difference was recorded for SLA, BMP-2, BMP-7 and AA. In conclusion, a beneficial biological effect of a chemical immobilization method of BMP-2, BMP-7 and alendronate onto titanium surfaces on BMSCs was proven.
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Affiliation(s)
- Peer W Kämmerer
- Department of Oral- and Maxillofacial Surgery, University Medical Center Mainz, Mainz, Germany
| | - Andreas M Pabst
- Department of Oral- and Maxillofacial Surgery, Federal Armed Forces Hospital, Koblenz, Germany
| | - Michael Dau
- Department of Oral- and Maxillofacial Surgery, University Medical Center Rostock, Rostock, Germany
| | - Henning Staedt
- Private Practice and Department of Prosthodontics and Materials Science, University Medical Center Rostock, Rostock, Germany
| | - Bilal Al-Nawas
- Department of Oral- and Maxillofacial Surgery, University Medical Center Mainz, Mainz, Germany
| | - Martin Heller
- Department of Gynecology, Johannes Gutenberg University Medical Center, Mainz, Germany
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11
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Marycz K, Alicka M, Kornicka-Garbowska K, Polnar J, Lis-Bartos A, Wiglusz RJ, Roecken M, Nedelec JM. Promotion through external magnetic field of osteogenic differentiation potential in adipose-derived mesenchymal stem cells: Design of polyurethane/poly(lactic) acid sponges doped with iron oxide nanoparticles. J Biomed Mater Res B Appl Biomater 2019; 108:1398-1411. [PMID: 31513334 DOI: 10.1002/jbm.b.34488] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2019] [Revised: 08/19/2019] [Accepted: 08/29/2019] [Indexed: 12/28/2022]
Abstract
Recently, iron oxide nanoparticles (IONPs) have gathered special attention in regenerative medicine. Owing to their magnetic and bioactive properties, IONPs are utilized in the fabrication of novel biomaterials. Yet, there was no report regarding thermoplastic polyurethane (TPU) and poly(lactic acid) (PLA) polymer doped with IONPs on osteogenic differentiation of mesenchymal stem cells. Thus the objectives of presented study was to: (a) fabricate magnetic TPU + PLA sponges doped with iron (III) oxide Fe2 O3 nanoparticles; (b) investigate the effects of biomaterial and its exposition to static magnetic field (MF) on osteogenic differentiation, proliferation, and apoptosis in adipose-derived mesenchymal stem cells (ASCs). TPU + PLA sponges were prepared using solvent casting technique while incorporation of the Fe2 O3 nanoparticles was performed with solution cast method. RT-PCR was applied to evaluate expression of osteogenic-related genes and integrin's in cells cultured on fabricated materials with or without the stimulation of static MF. MF stimulation enhanced the expression of osteopontin and collagen type I while decreased expression of bone morphogenetic protein 2 in tested magnetic materials-TPU + PLA/1% Fe2 O3 and TPU + PLA/5% Fe2 O3 . Therefore, TPU + PLA sponges doped with IONPs and exposure to MF resulted in improved osteogenic differentiation of ASC.
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Affiliation(s)
- Krzysztof Marycz
- Department of Experimental Biology, Wroclaw University of Environmental and Life Sciences, Wroclaw, Poland.,Faculty of Veterinary Medicine, Equine Clinic - Equine Surgery, Justus-Liebig-University, Gießen, Germany
| | - Michalina Alicka
- Department of Experimental Biology, Wroclaw University of Environmental and Life Sciences, Wroclaw, Poland
| | | | - Joanna Polnar
- Faculty of Materials Science and Ceramics, Department of Ceramics and Refractories, AGH University of Science and Technology, Krakow, Poland
| | - Anna Lis-Bartos
- Faculty of Materials Science and Ceramics, Department of Biomaterials and Composites, AGH University of Science and Technology, Krakow, Poland
| | - Rafał J Wiglusz
- Institute of Low Temperature and Structure Research, Polish Academy of Sciences, Wroclaw, Poland
| | - Michael Roecken
- Faculty of Veterinary Medicine, Equine Clinic - Equine Surgery, Justus-Liebig-University, Gießen, Germany
| | - Jean-Marie Nedelec
- Université Clermont Auvergne, CNRS, SIGMA Clermont, ICCF, Clermont-Ferrand, France
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12
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Marycz K, Kornicka K, Röcken M. Static Magnetic Field (SMF) as a Regulator of Stem Cell Fate - New Perspectives in Regenerative Medicine Arising from an Underestimated Tool. Stem Cell Rev Rep 2019; 14:785-792. [PMID: 30225821 PMCID: PMC6223715 DOI: 10.1007/s12015-018-9847-4] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Tissue engineering and stem cell-based therapies are one of the most rapidly developing fields in medical sciences. Therefore, much attention has been paid to the development of new drug-delivery systems characterized by low cytotoxicity, high efficiency and controlled release. One of the possible strategies to achieve these goals is the application of magnetic field and/or magnetic nanoparticles, which have been shown to exert a wide range of effects on cellular metabolism. Static magnetic field (SMF) has been commonly used in medicine as a tool to increase wound healing, bone regeneration and as a component of magnetic resonance technique. However, recent data shed light on deeper mechanism of SMF action on physiological properties of different cell populations, including stem cells. In the present review, we focused on SMF effects on stem cell biology and its possible application as a tool for controlled drug delivery. We also highlighted the perspectives, in which SMF can be used in future therapies in tissue engineering due to its easy application and a wide range of possible effects on cells and organisms.
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Affiliation(s)
- Krzysztof Marycz
- Department of Experimental Biology, Wroclaw University of Environmental and Life Sciences, Norwida 27B, Wrocław, Poland. .,Faculty of Veterinary Medicine, Equine Clinic - Equine Surgery, Justus-Liebig-University, 35392, Gießen, Germany.
| | - K Kornicka
- Department of Experimental Biology, Wroclaw University of Environmental and Life Sciences, Norwida 27B, Wrocław, Poland
| | - M Röcken
- Faculty of Veterinary Medicine, Equine Clinic - Equine Surgery, Justus-Liebig-University, 35392, Gießen, Germany
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Sun M, Chi G, Li P, Lv S, Xu J, Xu Z, Xia Y, Tan Y, Xu J, Li L, Li Y. Effects of Matrix Stiffness on the Morphology, Adhesion, Proliferation and Osteogenic Differentiation of Mesenchymal Stem Cells. Int J Med Sci 2018; 15:257-268. [PMID: 29483817 PMCID: PMC5820855 DOI: 10.7150/ijms.21620] [Citation(s) in RCA: 161] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2017] [Accepted: 12/21/2017] [Indexed: 01/05/2023] Open
Abstract
BMMSCs have drawn great interest in tissue engineering and regenerative medicine attributable to their multi-lineage differentiation capacity. Increasing evidence has shown that the mechanical stiffness of extracellular matrix is a critical determinant for stem cell behaviors. However, it remains unknown how matrix stiffness influences MSCs commitment with changes in cell morphology, adhesion, proliferation, self-renewal and differentiation. We employed fibronectin coated polyacrylamide hydrogels with variable stiffnesses ranging from 13 to 68 kPa to modulate the mechanical environment of BMMSCs and found that the morphology and adhesion of BMMSCs were highly dependent on mechanical stiffness. Cells became more spread and more adhesive on substrates of higher stiffness. Similarly, the proliferation of BMMSCs increased as stiffness increased. Sox2 expression was lower during 4h to 1 week on the 13-16 kPa and 62-68 kPa, in contrast, it was higher during 4h to 1 week on the 48-53 kPa. Oct4 expression on 13-16 kPa was higher than 48-53 kPa at 4h, and it has no significant differences at other time point among three different stiffness groups. On 62-68 kPa, BMMSCs were able to be induced toward osteogenic phenotype and generated a markedly high level of RUNX2, ALP, and Osteopontin. The cells exhibited a polygonal morphology and larger spreading area. These results suggest that matrix stiffness modulates commitment of BMMSCs. Our findings may eventually aid in the development of novel, effective biomaterials for the applications in tissue engineering.
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Affiliation(s)
- Meiyu Sun
- The Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune College of Medicine, Jilin University, 130021, People's Republic of China
| | - Guangfan Chi
- The Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune College of Medicine, Jilin University, 130021, People's Republic of China
| | - Pengdong Li
- The Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune College of Medicine, Jilin University, 130021, People's Republic of China
| | - Shuang Lv
- The Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune College of Medicine, Jilin University, 130021, People's Republic of China
| | - Juanjuan Xu
- The Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune College of Medicine, Jilin University, 130021, People's Republic of China
| | - Ziran Xu
- The Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune College of Medicine, Jilin University, 130021, People's Republic of China
| | - Yuhan Xia
- The Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune College of Medicine, Jilin University, 130021, People's Republic of China
| | - Ye Tan
- The Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune College of Medicine, Jilin University, 130021, People's Republic of China
| | - Jiayi Xu
- The Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune College of Medicine, Jilin University, 130021, People's Republic of China
| | - Lisha Li
- The Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune College of Medicine, Jilin University, 130021, People's Republic of China
| | - Yulin Li
- The Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune College of Medicine, Jilin University, 130021, People's Republic of China
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Xia P, Wang X, Qu Y, Lin Q, Cheng K, Gao M, Ren S, Zhang T, Li X. TGF-β1-induced chondrogenesis of bone marrow mesenchymal stem cells is promoted by low-intensity pulsed ultrasound through the integrin-mTOR signaling pathway. Stem Cell Res Ther 2017; 8:281. [PMID: 29237506 PMCID: PMC5729425 DOI: 10.1186/s13287-017-0733-9] [Citation(s) in RCA: 58] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2017] [Revised: 11/19/2017] [Accepted: 11/23/2017] [Indexed: 02/06/2023] Open
Abstract
Background Low-intensity pulsed ultrasound (LIPUS) is a mechanical stimulus that plays a key role in regulating the differentiation of bone marrow mesenchymal stem cells (BMSCs). However, the way in which it affects the chondrogenic differentiation of BMSCs remains unknown. In this study, we aimed to investigate whether LIPUS is able to influence TGF-β1-induced chondrogenesis of BMSCs through the integrin-mechanistic target of the Rapamycin (mTOR) signaling pathway. Methods BMSCs were isolated from rat bone marrow and cultured in either standard or TGF-β1-treated culture medium. BMSCs were then subjected to LIPUS at a frequency of 3 MHz and a duty cycle of 20%, and integrin and mTOR inhibitors added in order to analyze their influence on cell differentiation. BMSCs were phenotypically analyzed by flow cytometry and the degree of chondrogenesis evaluated through toluidine blue staining, immunofluorescence, and immunocytochemistry. Furthermore, expression of COL2, aggrecan, SOX9, and COL1 was assessed by qRT-PCR and western blot analysis. Results We found that LIPUS promoted TGF-β1-induced chondrogenesis of BMSCs, represented by increased expression of COL2, aggrecan and SOX9 genes, and decreased expression of COL1. Notably, these effects were prevented following addition of integrin and mTOR inhibitors. Conclusions Taken together, these results indicate that mechanical stimulation combined with LIPUS promotes TGF-β1-induced chondrogenesis of BMSCs through the integrin-mTOR signaling pathway.
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Affiliation(s)
- Peng Xia
- Department of Rehabilitation Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China
| | - Xiaoju Wang
- Department of Rehabilitation Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China
| | - Yanping Qu
- Department of Rehabilitation Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China
| | - Qiang Lin
- Department of Rehabilitation Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China
| | - Kai Cheng
- Department of Rehabilitation Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China
| | - Mingxia Gao
- Department of Rehabilitation Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China
| | - Shasha Ren
- Department of Rehabilitation Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China
| | - Tingting Zhang
- Department of Rehabilitation Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China
| | - Xueping Li
- Department of Rehabilitation Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China.
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15
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Popa EG, Santo VE, Rodrigues MT, Gomes ME. Magnetically-Responsive Hydrogels for Modulation of Chondrogenic Commitment of Human Adipose-Derived Stem Cells. Polymers (Basel) 2016; 8:E28. [PMID: 30979122 PMCID: PMC6432525 DOI: 10.3390/polym8020028] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2015] [Revised: 01/08/2016] [Accepted: 01/19/2016] [Indexed: 01/29/2023] Open
Abstract
Magnetic nanoparticles (MNPs) are attractive tools to overcome limitations of current regenerative medicine strategies, demonstrating potential to integrate therapeutic and diagnostic functionalities in highly controlled systems. In traditional tissue engineering (TE) approaches, the MNPs association with stem cells in a three-dimensional (3D) template offers the possibility to achieve a mechano-magnetic responsive system, enabling remote control actuation. Herein, we propose to study the role of MNPs integrated in κ-carrageenan (κC) hydrogels in the cellular response of human adipose-derived stem cells (hASCs) aiming at cartilage TE applications. The results indicated that the concentration of MNPs in the κC hydrogels influences cellular behavior, tuning a positive effect on cell viability, cell content and metabolic activity of hASCs, with the most promising outcomes found in 5% MNP-κC matrices. Although hASCs laden in MNPs-free- and MNPs-κC hydrogels showed similar metabolic and proliferation levels, MNPs κC hydrogels under magnetic actuation evidenced an instructive effect on hASCs, at a gene expression level, towards chondrogenic phenotype even in basic medium cultures. Therefore, the MNPs-based systems developed in this study may contribute to advanced strategies towards cartilage-like engineered substitutes.
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Affiliation(s)
- Elena G Popa
- 3B's Research Group-Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Taipas, Guimarães 4806-909, Portugal.
- ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.
| | - Vítor E Santo
- 3B's Research Group-Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Taipas, Guimarães 4806-909, Portugal.
- ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.
| | - Márcia T Rodrigues
- 3B's Research Group-Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Taipas, Guimarães 4806-909, Portugal.
- ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.
| | - Manuela E Gomes
- 3B's Research Group-Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Taipas, Guimarães 4806-909, Portugal.
- ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.
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Connell JJ, Patrick PS, Yu Y, Lythgoe MF, Kalber TL. Advanced cell therapies: targeting, tracking and actuation of cells with magnetic particles. Regen Med 2015; 10:757-72. [PMID: 26390317 DOI: 10.2217/rme.15.36] [Citation(s) in RCA: 54] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Regenerative medicine would greatly benefit from a new platform technology that enabled measurable, controllable and targeting of stem cells to a site of disease or injury in the body. Superparamagnetic iron-oxide nanoparticles offer attractive possibilities in biomedicine and can be incorporated into cells, affording a safe and reliable means of tagging. This review describes three current and emerging methods to enhance regenerative medicine using magnetic particles to guide therapeutic cells to a target organ; track the cells using MRI and assess their spatial localization with high precision and influence the behavior of the cell using magnetic actuation. This approach is complementary to the systemic injection of cell therapies, thus expanding the horizon of stem cell therapeutics.
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Affiliation(s)
- John J Connell
- UCL Centre of Advanced Biomedical Imaging, Division of Medicine, University College London, Paul O'Gorman Building, 72 Huntley Street, London, WC1E 6DD, UK
| | - P Stephen Patrick
- UCL Centre of Advanced Biomedical Imaging, Division of Medicine, University College London, Paul O'Gorman Building, 72 Huntley Street, London, WC1E 6DD, UK
| | - Yichao Yu
- UCL Centre of Advanced Biomedical Imaging, Division of Medicine, University College London, Paul O'Gorman Building, 72 Huntley Street, London, WC1E 6DD, UK
| | - Mark F Lythgoe
- UCL Centre of Advanced Biomedical Imaging, Division of Medicine, University College London, Paul O'Gorman Building, 72 Huntley Street, London, WC1E 6DD, UK
| | - Tammy L Kalber
- UCL Centre of Advanced Biomedical Imaging, Division of Medicine, University College London, Paul O'Gorman Building, 72 Huntley Street, London, WC1E 6DD, UK
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Boda SK, Thrivikraman G, Basu B. Magnetic field assisted stem cell differentiation – role of substrate magnetization in osteogenesis. J Mater Chem B 2015; 3:3150-3168. [DOI: 10.1039/c5tb00118h] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Substrate magnetization as a tool for modulating the osteogenesis of human mesenchymal stem cells for bone tissue engineering applications.
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Affiliation(s)
- Sunil Kumar Boda
- Laboratory for Biomaterials
- Materials Research Centre
- Indian Institute of Science
- Bangalore – 560012
- India
| | - Greeshma Thrivikraman
- Laboratory for Biomaterials
- Materials Research Centre
- Indian Institute of Science
- Bangalore – 560012
- India
| | - Bikramjit Basu
- Laboratory for Biomaterials
- Materials Research Centre
- Indian Institute of Science
- Bangalore – 560012
- India
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18
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Kasten A, Naser T, Brüllhoff K, Fiedler J, Müller P, Möller M, Rychly J, Groll J, Brenner RE. Guidance of mesenchymal stem cells on fibronectin structured hydrogel films. PLoS One 2014; 9:e109411. [PMID: 25329487 PMCID: PMC4198140 DOI: 10.1371/journal.pone.0109411] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2014] [Accepted: 08/29/2014] [Indexed: 12/21/2022] Open
Abstract
Designing of implant surfaces using a suitable ligand for cell adhesion to stimulate specific biological responses of stem cells will boost the application of regenerative implants. For example, materials that facilitate rapid and guided migration of stem cells would promote tissue regeneration. When seeded on fibronectin (FN) that was homogeneously immmobilized to NCO-sP(EO-stat-PO), which otherwise prevents protein binding and cell adhesion, human mesenchymal stem cells (MSC) revealed a faster migration, increased spreading and a more rapid organization of different cellular components for cell adhesion on fibronectin than on a glass surface. To further explore, how a structural organization of FN controls the behavior of MSC, adhesive lines of FN with varying width between 10 µm and 80 µm and spacings between 5 µm and 20 µm that did not allow cell adhesion were generated. In dependance on both line width and gaps, cells formed adjacent cell contacts, were individually organized in lines, or bridged the lines. With decreasing sizes of FN lines, speed and directionality of cell migration increased, which correlated with organization of the actin cytoskeleton, size and shape of the nuclei as well as of focal adhesions. Together, defined FN lines and gaps enabled a fine tuning of the structural organization of cellular components and migration. Microstructured adhesive substrates can mimic the extracellular matrix in vivo and stimulate cellular mechanisms which play a role in tissue regeneration.
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Affiliation(s)
- Annika Kasten
- Laboratory of Cell Biology, Rostock University Medical Center, Rostock, Germany
| | - Tamara Naser
- Division for Biochemistry of Joint and Connective Tissue Diseases of the Orthopedic Department, University of Ulm, Ulm, Germany
| | - Kristina Brüllhoff
- DWI Leibniz Institute for Interactive Materials and Institute of Technical and Macromolecular Chemistry, RWTH Aachen University, Aachen, Germany
| | - Jörg Fiedler
- Division for Biochemistry of Joint and Connective Tissue Diseases of the Orthopedic Department, University of Ulm, Ulm, Germany
| | - Petra Müller
- Laboratory of Cell Biology, Rostock University Medical Center, Rostock, Germany
| | - Martin Möller
- DWI Leibniz Institute for Interactive Materials and Institute of Technical and Macromolecular Chemistry, RWTH Aachen University, Aachen, Germany
| | - Joachim Rychly
- Laboratory of Cell Biology, Rostock University Medical Center, Rostock, Germany
- * E-mail:
| | - Jürgen Groll
- DWI Leibniz Institute for Interactive Materials and Institute of Technical and Macromolecular Chemistry, RWTH Aachen University, Aachen, Germany
- Department and Chair of Functional Materials in Medicine and Dentistry, University of Würzburg, Würzburg, Germany
| | - Rolf E. Brenner
- Division for Biochemistry of Joint and Connective Tissue Diseases of the Orthopedic Department, University of Ulm, Ulm, Germany
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19
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Wang Q, Wu W, Han X, Zheng A, Lei S, Wu J, Chen H, He C, Luo F, Liu X. Osteogenic differentiation of amniotic epithelial cells: synergism of pulsed electromagnetic field and biochemical stimuli. BMC Musculoskelet Disord 2014; 15:271. [PMID: 25112311 PMCID: PMC4267405 DOI: 10.1186/1471-2474-15-271] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2014] [Accepted: 06/28/2014] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Pulsed electromagnetic field (PEMF) is a non-invasive physical therapy used in the treatment of fracture nonunion or delayed healing. PEMF can facilitate the osteogenic differentiation of bone marrow mesenchymal stem cells in vitro. Amniotic epithelial cells (AECs) have been proposed as a potential source of stem cells for cell therapy. However, whether PEMF could modulate the osteogenic differentiation of AECs is unknown. In the present study, the effects of PEMF on the osteogenic differentiation of AECs were investigated. METHODS AECs were isolated from amniotic membrane of human placenta by trypsin digestion and were induced by PEMF and/or osteo-induction medium. After 21 days we used real time RT-PCR and immunocytochemistry to study the expression of osteoblast markers. The signal transduction of osteogenesis was further investigated. RESULTS The PEMF stimulation, or osteo-induction medium alone could induce osteogenic differentiation of AECs, as shown by expression of osteoblast specific genes and proteins including alkaline phosphatase and osteocalcin. Furthermore, a combination of PEMF and osteo-induction medium had synergy effects on osteogenic differentiation. In our study, the gene expression of BMP-2, Runx2, β-catenin, Nrf2, Keap1 and integrinβ1 were up-regulated in the osteogenic differentiation of AECs induced by PEMF and/or osteo-induction medium. CONCLUSIONS Combined application of PEMF and osteo-induction medium is synergistic for the osteogenic differentiation of AECs. It might be a novel approach in the bone regenerative medicine.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - Xiaojing Liu
- Center of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, P, R, China.
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20
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Chen SK, Chung CA, Cheng YC, Huang CJ, Ruaan RC, Chen WY, Li C, Tsao CW, Hu WW, Chien CC. Hydrostatic pressure enhances mitomycin C induced apoptosis in urothelial carcinoma cells. Urol Oncol 2013; 32:26.e17-24. [PMID: 23403205 DOI: 10.1016/j.urolonc.2012.09.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2012] [Revised: 09/13/2012] [Accepted: 09/13/2012] [Indexed: 10/27/2022]
Abstract
OBJECTIVES Urothelial carcinoma (UC) of the bladder is the second most common cancer of the genitourinary system. Clinical UC treatment usually involves transurethral resection of the bladder tumor followed by adjuvant intravesical immunotherapy or chemotherapy to prevent recurrence. Intravesical chemotherapy induces fewer side effects than immunotherapy but is less effective at preventing tumor recurrence. Improvement to intravesical chemotherapy is, therefore, needed. METHODS AND MATERIALS Cellular effects of mitomycin C (MMC) and hydrostatic pressure on UC BFTC905 cells were assessed. The viability of the UC cells was determined using cellular proliferation assay. Changes in apoptotic function were evaluated by caspase 3/7 activities, expression of FasL, and loss of mitochondrial membrane potential. RESULTS Reduced cell viability was associated with increasing hydrostatic pressure. Caspase 3/7 activities were increased following treatment of the UC cells with MMC or hydrostatic pressure. In combination with 10 kPa hydrostatic pressure, MMC treatment induced increasing FasL expression. The mitochondria of UC cells displayed increasingly impaired membrane potentials following a combined treatment with 10 μg/ml MMC and 10 kPa hydrostatic pressure. CONCLUSIONS Both MMC and hydrostatic pressure can induce apoptosis in UC cells through an extrinsic pathway. Hydrostatic pressure specifically increases MMC-induced apoptosis and might minimize the side effects of the chemotherapy by reducing the concentration of the chemical agent. This study provides a new and alternative approach for treatment of patients with UC following transurethral resection of the bladder tumor.
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Affiliation(s)
- Shao-Kuan Chen
- Department of Urology, Sijhih Cathay General Hospital, New Taipei City, Taiwan; Department of Mechanical Engineering, National Central University, Jhongli, Taiwan; School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan
| | - Chih-Ang Chung
- Department of Mechanical Engineering, National Central University, Jhongli, Taiwan; Institute of Biomedical Engineering, National Central University, Jhongli, Taiwan
| | - Yu-Che Cheng
- Institute of Biomedical Engineering, National Central University, Jhongli, Taiwan; Department of Medical Research, Cathay General Hospital, Taipei, Taiwan
| | - Chi-Jung Huang
- School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan; Department of Medical Research, Cathay General Hospital, Taipei, Taiwan; Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan
| | - Ruoh-Chyu Ruaan
- Institute of Biomedical Engineering, National Central University, Jhongli, Taiwan; Department of Chemical and Materials Engineering, National Central University, Jhongli, Taiwan
| | - Wen-Yih Chen
- Department of Chemical and Materials Engineering, National Central University, Jhongli, Taiwan
| | - Chuan Li
- Department of Mechanical Engineering, National Central University, Jhongli, Taiwan
| | - Chia-Wen Tsao
- Department of Mechanical Engineering, National Central University, Jhongli, Taiwan
| | - Wei-Wen Hu
- Department of Chemical and Materials Engineering, National Central University, Jhongli, Taiwan
| | - Chih-Cheng Chien
- School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan; Institute of Biomedical Engineering, National Central University, Jhongli, Taiwan; Department of Medical Research, Cathay General Hospital, Taipei, Taiwan; Department of Anesthesiology, Sijhih Cathay General Hospital, Sijhih District, New Taipei City, Taiwan.
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21
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Higuchi A, Ling QD, Chang Y, Hsu ST, Umezawa A. Physical Cues of Biomaterials Guide Stem Cell Differentiation Fate. Chem Rev 2013; 113:3297-328. [DOI: 10.1021/cr300426x] [Citation(s) in RCA: 345] [Impact Index Per Article: 28.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- Akon Higuchi
- Department of Chemical and Materials
Engineering, National Central University, Jhongli, Taoyuan 32001, Taiwan
- Department of Reproductive Biology, National Research Institute for Child Health and Development, 2-10-1 Okura,
Setagaya-ku, Tokyo 157-8535, Japan
- Cathay Medical Research Institute, Cathay General Hospital, No. 32, Ln 160, Jian-Cheng Road, Hsi-Chi City, Taipei 221, Taiwan
| | - Qing-Dong Ling
- Cathay Medical Research Institute, Cathay General Hospital, No. 32, Ln 160, Jian-Cheng Road, Hsi-Chi City, Taipei 221, Taiwan
- Institute of Systems Biology
and Bioinformatics, National Central University, No. 300 Jhongda Rd., Jhongli, Taoyuan 32001, Taiwan
| | - Yung Chang
- Department of Chemical Engineering, R&D Center for Membrane Technology, Chung Yuan Christian University, 200 Chung-Bei Rd., Jhongli, Taoyuan 320, Taiwan
| | - Shih-Tien Hsu
- Taiwan Landseed Hospital, 77 Kuangtai Road, Pingjen City, Tao-Yuan
County 32405, Taiwan
| | - Akihiro Umezawa
- Department of Reproductive Biology, National Research Institute for Child Health and Development, 2-10-1 Okura,
Setagaya-ku, Tokyo 157-8535, Japan
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Beer MV, Rech C, Gasteier P, Sauerzapfe B, Salber J, Ewald A, Möller M, Elling L, Groll J. The next step in biomimetic material design: poly-LacNAc-mediated reversible exposure of extra cellular matrix components. Adv Healthc Mater 2013. [PMID: 23184377 DOI: 10.1002/adhm.201200080] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Affiliation(s)
- Meike V Beer
- Department of Functional Materials in Medicine and Dentistry, University of Würzburg, Würzburg, Germany
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Bulnheim U, Müller P, Neumann HG, Peters K, Unger RE, Kirkpatrick CJ, Rychly J. Endothelial cells stimulate osteogenic differentiation of mesenchymal stem cells on calcium phosphate scaffolds. J Tissue Eng Regen Med 2012; 8:831-40. [PMID: 23038605 DOI: 10.1002/term.1590] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2011] [Revised: 01/25/2012] [Accepted: 07/07/2012] [Indexed: 12/14/2022]
Abstract
The interaction of mesenchymal stem cells (MSCs) with endothelium in vivo is significant for regenerative processes in organisms. To design concepts for tissue engineering for bone regeneration based on this interaction, the osteogenic differentiation of human bone marrow-derived MSCs in a co-culture with human dermal microvascular endothelial cells (HDMECs) was studied. The experiments were focussed on the regulation of MSCs in a co-culture with HDMECs on different calcium phosphate scaffolds. Alkaline phosphatase (ALP) activity and mRNA expression of various osteogenic markers increased significantly when cells were co-cultured on materials with calcium phosphate scaffolds compared to tissue culture polystyrene or when MSCs were cultured alone. In addition, it was observed that the expression of osteopontin and osteocalcin was highly sensitive to the substrate for cell adhesion. Whereas these late osteogenic markers were down-regulated in co-cultures on polystyrene, they were up-regulated on calcium phosphate and moreover, were differentially expressed on the three calcium phosphate scaffolds tested. To enhance the osteogenic differentiation of MSCs in a co-culture, direct cell-cell interactions were required. Concerning molecular mechanisms in the interactions between both cell types, it was found that connexin 43 was expressed in contact sites and more apparently, endothelial cells grew over the MSCs, which facilitated direct cellular interactions mediated by various adhesion receptors. This study revealed significant findings for the design of implant materials suitable for regeneration of bone by stimulating the functional interaction of MSCs with endothelial cells.
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Affiliation(s)
- Ulrike Bulnheim
- Laboratory of Cell Biology, Medical Faculty, University of Rostock, Schillingallee 69, 18057, Rostock, Germany
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Panseri S, Cunha C, D'Alessandro T, Sandri M, Giavaresi G, Marcacci M, Hung CT, Tampieri A. Intrinsically superparamagnetic Fe-hydroxyapatite nanoparticles positively influence osteoblast-like cell behaviour. J Nanobiotechnology 2012; 10:32. [PMID: 22828388 PMCID: PMC3458931 DOI: 10.1186/1477-3155-10-32] [Citation(s) in RCA: 84] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2012] [Accepted: 06/18/2012] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Superparamagnetic nanoparticles (MNPs) have been progressively explored for their potential in biomedical applications and in particular as a contrast agent for diagnostic imaging, for magnetic drug delivery and more recently for tissue engineering applications. Considering the importance of having safe MNPs for such applications, and the essential role of iron in bone remodelling, this study developed and analysed novel biocompatible and bioreabsorbable superparamagnetic nanoparticles, that avoid the use of poorly tolerated magnetite based nanoparticles, for bone tissue engineering applications. RESULTS MNPs were obtained by doping hydroxyapatite (HA) with Fe ions, by directly substituting Fe2+ and Fe3+ into the HA structure yielding superparamagnetic bioactive phase. In the current study, we have investigated the effects of increasing concentrations (2000 μg/ml; 1000 μg/ml; 500 μg/ml; 200 μg/ml) of FeHA MNPs in vitro using Saos-2 human osteoblast-like cells cultured for 1, 3 and 7 days with and without the exposure to a static magnetic field of 320 mT. Results demonstrated not only a comparable osteoblast viability and morphology, but increased in cell proliferation, when compared to a commercially available Ha nanoparticles, even with the highest dose used. Furthermore, FeHA MNPs exposure to the static magnetic field resulted in a significant increase in cell proliferation throughout the experimental period, and higher osteoblast activity.In vivo preliminary results demonstrated good biocompatibility of FeHA superparamagnetic material four weeks after implantation into a critical size lesion of the rabbit condyle. CONCLUSIONS The results of the current study suggest that these novel FeHA MNPs may be particularly relevant for strategies of bone tissue regeneration and open new perspectives for the application of a static magnetic field in a clinical setting of bone replacement, either for diagnostic imaging or magnetic drug delivery.
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Affiliation(s)
- Silvia Panseri
- Laboratory of Biomechanics and Technology Innovation, Rizzoli Orthopaedic Institute, Bologna, Italy.
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Yan YX, Gong YW, Guo Y, Lv Q, Guo C, Zhuang Y, Zhang Y, Li R, Zhang XZ. Mechanical strain regulates osteoblast proliferation through integrin-mediated ERK activation. PLoS One 2012; 7:e35709. [PMID: 22539993 PMCID: PMC3335094 DOI: 10.1371/journal.pone.0035709] [Citation(s) in RCA: 93] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2011] [Accepted: 03/20/2012] [Indexed: 01/21/2023] Open
Abstract
Mechanical strain plays a critical role in the proliferation, differentiation and maturation of bone cells. As mechanical receptor cells, osteoblasts perceive and respond to stress force, such as those associated with compression, strain and shear stress. However, the underlying molecular mechanisms of this process remain unclear. Using a four-point bending device, mouse MC3T3-E1 cells was exposed to mechanical tensile strain. Cell proliferation was determined to be most efficient when stimulated once a day by mechanical strain at a frequency of 0.5 Hz and intensities of 2500 µε with once a day, and a periodicity of 1 h/day for 3 days. The applied mechanical strain resulted in the altered expression of 1992 genes, 41 of which are involved in the mitogen-activated protein kinase (MAPK) signaling pathway. Activation of ERK by mechanical strain promoted cell proliferation and inactivation of ERK by PD98059 suppressed proliferation, confirming that ERK plays an important role in the response to mechanical strain. Furthermore, the membrane-associated receptors integrin β1 and integrin β5 were determined to regulate ERK activity and the proliferation of mechanical strain-treated MC3T3-E1 cells in opposite ways. The knockdown of integrin β1 led to the inhibition of ERK activity and cell proliferation, whereas the knockdown of integrin β5 led to the enhancement of both processes. This study proposes a novel mechanism by which mechanical strain regulates bone growth and remodeling.
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Affiliation(s)
- Yu-xian Yan
- Institute of Medical Equipment, Academy of Military Medical Science, Tianjin, China
- Experiment Management Center of Medical College of People's Armed Police Forces, TianJin, China
| | - Yuan-wei Gong
- Institute of Medical Equipment, Academy of Military Medical Science, Tianjin, China
| | - Yong Guo
- Institute of Medical Equipment, Academy of Military Medical Science, Tianjin, China
| | - Qi Lv
- Experiment Management Center of Medical College of People's Armed Police Forces, TianJin, China
| | - Chun Guo
- Institute of Medical Equipment, Academy of Military Medical Science, Tianjin, China
| | - Yan Zhuang
- Experiment Management Center of Medical College of People's Armed Police Forces, TianJin, China
| | - Yuan Zhang
- Experiment Management Center of Medical College of People's Armed Police Forces, TianJin, China
| | - Ruixin Li
- Institute of Medical Equipment, Academy of Military Medical Science, Tianjin, China
| | - Xi-zheng Zhang
- Institute of Medical Equipment, Academy of Military Medical Science, Tianjin, China
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Dado D, Sagi M, Levenberg S, Zemel A. Mechanical control of stem cell differentiation. Regen Med 2012; 7:101-16. [DOI: 10.2217/rme.11.99] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
Numerous studies have focused on identifying the chemical and biological factors that govern the differentiation of stem cells; however, recent research has shown that mechanical cues may play an equally important role. Mechanical forces such as shear stresses and tensile loads, as well as the rigidity and topography of the extracellular matrix were shown to induce significant changes in the morphology and fate of stem cells. We survey experimental studies that focused on the response of stem cells to mechanical and geometrical properties of their environment and discuss the mechanical mechanisms that accompany their response including the remodeling of the cytoskeleton and determination of cell and nucleus size and shape.
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Affiliation(s)
- Dekel Dado
- Biomedical Engineering, Technion, Haifa, 32000, Israel
| | - Maayan Sagi
- Institute of Dental Sciences & the Fritz Haber Research Center, Hebrew-University, Hadassah Medical Center, Jerusalem, 91120, Israel
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Steinmetz NJ, Bryant SJ. The effects of intermittent dynamic loading on chondrogenic and osteogenic differentiation of human marrow stromal cells encapsulated in RGD-modified poly(ethylene glycol) hydrogels. Acta Biomater 2011; 7:3829-40. [PMID: 21742067 DOI: 10.1016/j.actbio.2011.06.031] [Citation(s) in RCA: 57] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2011] [Revised: 05/28/2011] [Accepted: 06/21/2011] [Indexed: 10/18/2022]
Abstract
Biochemical and biomechanical cues are known to influence the differentiation of stem cells. Biomechanical cues arise from cellular interactions with their surrounding matrix and from applied forces. This study investigates the role of biomechanical cues in chondrogenic and osteogenic differentiation of human marrow stromal cells (hMSC) when encapsulated in synthetic hydrogels. Poly(ethylene glycol) hydrogels were fabricated with tethered cell adhesion moieties, RGD. Cell-laden hydrogels were subjected to 4 h daily intermittent dynamic compressive loading (0.3Hz, 15% amplitude strain) for up to 14 days and the cell response evaluated by gene expression and matrix deposition for chondrogenic and osteogenic markers. The three-dimensional hydrogel supported chondrogenesis and osteogenesis under free swelling conditions, as shown by the up-regulation of cartilage-related markers (SOX9, Col II, Col X, and aggrecan) and staining for type II collagen and aggrecan and osteogenically by up-regulation of ALP and staining for type I collagen and for mineralization. However, under dynamic loading the expression of cartilage-related markers SOX9, Col II, Col X, and aggrecan were down-regulated, along with reduced aggrecan staining and no positive staining for type II collagen. Additionally, the bone-related markers RUNX2, Col I, and ALP were down-regulated and positive staining for type I collagen and mineralization was reduced. In conclusion, the selected loading regime appears to have an inhibitory effect on chondrogenesis and osteogenesis of hMSC encapsulated in PEG-RGD hydrogels after 14 days in culture, potentially due to overloading of the differentiating hMSC before sufficient pericellular matrix is produced and/or due to large strains, particularly for osteogenically differentiating hMSC.
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Lee WD, Hurtig MB, Kandel RA, Stanford WL. Membrane Culture of Bone Marrow Stromal Cells Yields Better Tissue Than Pellet Culture for Engineering Cartilage-Bone Substitute Biphasic Constructs in a Two-Step Process. Tissue Eng Part C Methods 2011; 17:939-48. [DOI: 10.1089/ten.tec.2011.0147] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Affiliation(s)
- Whitaik David Lee
- Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada
| | - Mark B. Hurtig
- Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada
| | - Rita A. Kandel
- Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada
- Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada
| | - William L. Stanford
- Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada
- Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario, Canada
- Sprott Centre for Stem Cell Research, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
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Anders T, Adamiak K, Keul H, Elling L, Möller M. Synthesis of a Difunctional Orthogonal Coupler for the Preparation of Carbohydrate-Functionalized sP(EO-stat-PO) Hydrogels. Macromol Biosci 2011; 11:1201-10. [DOI: 10.1002/mabi.201100041] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2011] [Revised: 04/15/2011] [Indexed: 11/11/2022]
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Delaine-Smith RM, Reilly GC. The effects of mechanical loading on mesenchymal stem cell differentiation and matrix production. VITAMINS AND HORMONES 2011; 87:417-80. [PMID: 22127254 DOI: 10.1016/b978-0-12-386015-6.00039-1] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Mesenchymal stem cells or stromal cells (MSCs) have the potential to be used therapeutically in tissue engineering and regenerative medicine to replace or restore the function of damaged tissues. Therefore, considerable effort has been ongoing in the research community to optimize culture conditions for predifferentiation of MSCs. All mesenchymal tissues are subjected to mechanical forces in vivo and all fully differentiated mesenchymal lineage cells respond to mechanical stimulation in vivo and in vitro. Therefore, it is not surprising that MSCs are highly mechanosensitive. We present a summary of current methods of mechanical stimulation of MSCs and an overview of the outcomes of the different mechanical culture techniques tested. Tissue engineers and stem cell researchers should be able to harness this mechanosensitivity to modulate MSC differentiation and matrix production; however, more research needs to be undertaken to understand the complex interactions between the mechanosensitive and biochemically stimulated differentiation pathways.
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Affiliation(s)
- Robin M Delaine-Smith
- The Kroto Research Institute, Department of Materials Science and Engineering, University of Sheffield, Sheffield, United Kingdom
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