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Aștilean Pertea AN, Dreancă A, Gog-Bogdan S, Sevastre B, Ungur A, Negoescu A, Taulescu M, Rotar O, Dindelegan M, Gherman LM, Magyari K, Oana L. Bone proliferation in osteoporotic experimental animals using alginate-pullulan-bioactive glass‑gold nanoparticles composite. Bone 2025:117439. [PMID: 40024425 DOI: 10.1016/j.bone.2025.117439] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Revised: 02/25/2025] [Accepted: 02/26/2025] [Indexed: 03/04/2025]
Abstract
In the present study, scaffold composites based on alginate-pullulan-bioactive glass‑gold nanoparticles were orthotopically implanted in an experimental model of delayed bone union, in rats, given by a metabolic pathology, namely osteoporosis. Differences between treated and untreated groups were observed and the efficacy of our biomaterial was evaluated by applying micro-CT imaging, together with histological evaluation of the osteoporotic animals with sub-critical bone defects, at 30 and 60 days. Osteoporosis was successfully induced by ovariectomy in 9-month-old rats, confirmed by micro-CT and histopathological analysis. A secondary complication from a cortical bone defect was further induced to study bone proliferation in such a delayed environment. The studied composite presents osteointegration and angiogenesis properties at 60 days post-implantation in the osteoporotic animals. These results are given by the micro-CT analysis in which higher bone mineral density and bone volume fraction were observed, alongside histopathology, stating a lack of tissue necrosis and inflammatory reaction and the presence of new woven islands within and around the implanted biomaterial. This is the first endeavor to treat cortical bone defects in osteoporotic animals using scaffold biopolymers containing bioactive glass‑gold nanoparticles instead of cement.
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Affiliation(s)
| | - Alexandra Dreancă
- Faculty of Veterinary Medicine, University of Agricultural Science and Veterinary Medicine, 400372 Cluj-Napoca, Romania.
| | - Sidonia Gog-Bogdan
- Faculty of Veterinary Medicine, University of Agricultural Science and Veterinary Medicine, 400372 Cluj-Napoca, Romania
| | - Bogdan Sevastre
- Faculty of Veterinary Medicine, University of Agricultural Science and Veterinary Medicine, 400372 Cluj-Napoca, Romania
| | - Andrei Ungur
- Faculty of Veterinary Medicine, University of Agricultural Science and Veterinary Medicine, 400372 Cluj-Napoca, Romania
| | - Andrada Negoescu
- Faculty of Veterinary Medicine, University of Agricultural Science and Veterinary Medicine, 400372 Cluj-Napoca, Romania
| | - Marian Taulescu
- Faculty of Veterinary Medicine, University of Agricultural Science and Veterinary Medicine, 400372 Cluj-Napoca, Romania
| | - Oana Rotar
- Faculty of Veterinary Medicine, University of Agricultural Science and Veterinary Medicine, 400372 Cluj-Napoca, Romania
| | - Maximilian Dindelegan
- Faculty of Medicine, Iuliu Hațieganu University of Medicine and Pharmacy "Iuliu Hatieganu", 400012 Cluj-Napoca, Romania
| | - Luciana-Mădălina Gherman
- Centre for Experimental Medicine, University of Medicine and Pharmacy "Iuliu Hatieganu", 400349 Cluj-Napoca, Romania
| | - Klara Magyari
- Nanostructured Materials and Bio-Nano-Interfaces Center, Interdisciplinary Research Institute on Bio-Nano-Sciences, Babes-Bolyai University, 400271 Cluj-Napoca, Romania; INSPIRE Research Platform InfoBioNano4Health & Biomedical Imaging, Babeș Bolyai University, 400084 Cluj-Napoca, Romania.
| | - Liviu Oana
- Faculty of Veterinary Medicine, University of Agricultural Science and Veterinary Medicine, 400372 Cluj-Napoca, Romania
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2
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Lange-Consiglio A, Tagliasacchi F, Cremonesi F, Gusmara C, Pollera C, Scarpa P, Gaspari G, Riccaboni P. Characterization of Urine-Derived Stromal/Stem Cells from Healthy Dogs and Dogs Affected by Chronic Kidney Disease (CKD). Animals (Basel) 2025; 15:242. [PMID: 39858242 PMCID: PMC11758669 DOI: 10.3390/ani15020242] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2024] [Revised: 01/02/2025] [Accepted: 01/10/2025] [Indexed: 01/27/2025] Open
Abstract
Urine-derived mesenchymal stromal/stem cells (USCs) could be a valuable source of cells in regenerative medicine because urine can be easily collected non-invasively. In this paper, USCs were isolated from both healthy dogs and dogs affected by chronic kidney disease (CKD), and the efficacy of collection methods (spontaneous micturition, bladder catheterization, and cystocentesis) were compared. Isolated cells were cultured in the presence of platelet-rich plasma and studied for their proliferative capacity (growth curve, doubling time, and colony forming unit), differentiation properties, expression of mesenchymal markers, and Klotho protein. Morphologically, all cells were elongated and fibroblast-like. USCs isolated from samples collected by spontaneous micturition and bladder catheterization failed to proliferate, whilst USCs obtained by cystocentesis showed a doubling time of 2.04 days in healthy dogs and 1.7 days in dogs with CKD (p < 0.05). Cells were able to differentiate into osteogenic, chondrogenic, and adipogenic lines, showed positive expression to mesenchymal/stem markers, negative expression to hematopoietic markers, and major histocompatibility complex (MHCII) antigen. Klotho protein expression was confirmed. This study confirmed that USCs from healthy and CKD dogs can act as stem cells, with those from sick dogs having greater proliferative ability with the potential for use as autologous therapies.
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Affiliation(s)
- Anna Lange-Consiglio
- Reproduction Laboratory, Department of Veterinary Medicine and Animal Science, Università degli Studi di Milano, 26900 Lodi, Italy; (A.L.-C.); (F.C.)
| | - Filippo Tagliasacchi
- Department of Veterinary Medicine and Animal Science, Università degli Studi di Milano, 26900 Lodi, Italy; (F.T.); (C.G.); (C.P.); (P.S.); (P.R.)
| | - Fausto Cremonesi
- Reproduction Laboratory, Department of Veterinary Medicine and Animal Science, Università degli Studi di Milano, 26900 Lodi, Italy; (A.L.-C.); (F.C.)
| | - Claudia Gusmara
- Department of Veterinary Medicine and Animal Science, Università degli Studi di Milano, 26900 Lodi, Italy; (F.T.); (C.G.); (C.P.); (P.S.); (P.R.)
- Laboratorio di Malattie Infettive degli Animali (MiLab), Department of Veterinary Medicine and Animal Science, Università degli Studi di Milano, 26900 Lodi, Italy
| | - Claudia Pollera
- Department of Veterinary Medicine and Animal Science, Università degli Studi di Milano, 26900 Lodi, Italy; (F.T.); (C.G.); (C.P.); (P.S.); (P.R.)
| | - Paola Scarpa
- Department of Veterinary Medicine and Animal Science, Università degli Studi di Milano, 26900 Lodi, Italy; (F.T.); (C.G.); (C.P.); (P.S.); (P.R.)
| | - Giulia Gaspari
- Reproduction Laboratory, Department of Veterinary Medicine and Animal Science, Università degli Studi di Milano, 26900 Lodi, Italy; (A.L.-C.); (F.C.)
| | - Pietro Riccaboni
- Department of Veterinary Medicine and Animal Science, Università degli Studi di Milano, 26900 Lodi, Italy; (F.T.); (C.G.); (C.P.); (P.S.); (P.R.)
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3
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Yang HS, Zheng YX, Bai X, He XY, Wang TH. Application prospects of urine-derived stem cells in neurological and musculoskeletal diseases. World J Orthop 2024; 15:918-931. [DOI: 10.5312/wjo.v15.i10.918] [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: 04/24/2024] [Revised: 08/25/2024] [Accepted: 09/09/2024] [Indexed: 10/11/2024] Open
Abstract
Urine-derived stem cells (USCs) are derived from urine and harbor the potential of proliferation and multidirectional differentiation. Moreover, USCs could be reprogrammed into pluripotent stem cells [namely urine-derived induced pluripotent stem cells (UiPSCs)] through transcription factors, such as octamer binding transcription factor 4, sex determining region Y-box 2, kruppel-like factor 4, myelocytomatosis oncogene, and Nanog homeobox and protein lin-28, in which the first four are known as Yamanaka factors. Mounting evidence supports that USCs and UiPSCs possess high potential of neurogenic, myogenic, and osteogenic differentiation, indicating that they may play a crucial role in the treatment of neurological and musculoskeletal diseases. Therefore, we summarized the origin and physiological characteristics of USCs and UiPSCs and their therapeutic application in neurological and musculoskeletal disorders in this review, which not only contributes to deepen our understanding of hallmarks of USCs and UiPSCs but also provides the theoretical basis for the treatment of neurological and musculoskeletal disorders with USCs and UiPSCs.
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Affiliation(s)
- Hui-Si Yang
- Department of Neurology and National Traditional Chinese Medicine Clinical Research Base, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China
| | - Yue-Xiang Zheng
- Department of Neurology and National Traditional Chinese Medicine Clinical Research Base, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China
| | - Xue Bai
- Department of Neurology and National Traditional Chinese Medicine Clinical Research Base, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China
| | - Xiu-Ying He
- Department of Anesthesiology, Institute of Neurological Disease, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Ting-Hua Wang
- Department of Neurology and National Traditional Chinese Medicine Clinical Research Base, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China
- Department of Anesthesiology, Institute of Neurological Disease, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
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Yu P, Bosholm CC, Zhu H, Duan Z, Atala A, Zhang Y. Beyond waste: understanding urine's potential in precision medicine. Trends Biotechnol 2024; 42:953-969. [PMID: 38369434 PMCID: PMC11741143 DOI: 10.1016/j.tibtech.2024.01.009] [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: 08/29/2023] [Revised: 01/26/2024] [Accepted: 01/29/2024] [Indexed: 02/20/2024]
Abstract
Urine-derived stem cells (USCs) are a promising source of stem cells for cell therapy, renal toxicity drug testing, and renal disease biomarker discovery. Patients' own USCs can be used for precision medicine. In this review we first describe the isolation and characterization of USCs. We then discuss preclinical studies investigating the use of USCs in cell therapy, exploring the utility of USCs and USC-derived induced pluripotent stem cells (u-iPSCs) in drug toxicity testing, and investigating the use of USCs as biomarkers for renal disease diagnosis. Finally, we discuss the challenges of using USCs in these applications and provide insights into future research directions. USCs are a promising tool for advancing renal therapy, drug testing, and biomarker discovery. Further research is needed to explore their potential.
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Affiliation(s)
- Pengfei Yu
- The Fourth Department of Liver Disease, Beijing YouAn Hospital, Capital Medical University, Beijing, China; Wake Forest Institute for Regeneration Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA
| | - Carol Christine Bosholm
- Wake Forest Institute for Regeneration Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA
| | - Hainan Zhu
- Wake Forest Institute for Regeneration Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA
| | - Zhongping Duan
- The Fourth Department of Liver Disease, Beijing YouAn Hospital, Capital Medical University, Beijing, China
| | - Anthony Atala
- Wake Forest Institute for Regeneration Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA
| | - Yuanyuan Zhang
- Wake Forest Institute for Regeneration Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.
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Atia GA, Rashed F, Taher ES, Cho SG, Dayem AA, Soliman MM, Shalaby HK, Mohammed NA, Taymour N, El-Sherbiny M, Ebrahim E, Ramadan MM, Abdelkader A, Abdo M, Aldarmahi AA, Atwa AM, Bafail DA, Abdeen A. Challenges of therapeutic applications and regenerative capacities of urine based stem cells in oral, and maxillofacial reconstruction. Biomed Pharmacother 2024; 177:117005. [PMID: 38945084 DOI: 10.1016/j.biopha.2024.117005] [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: 03/31/2024] [Revised: 06/09/2024] [Accepted: 06/17/2024] [Indexed: 07/02/2024] Open
Abstract
Urine-derived stem cells (USCs) have gained the attention of researchers in the biomedical field in the past few years . Regarding the several varieties of cells that have been used for this purpose, USCs have demonstrated mesenchymal stem cell-like properties, such as differentiation and immunomodulation. Furthermore, they could be differentiated into several lineages. This is very interesting for regenerative techniques based on cell therapy. This review will embark on describing their separation, and profiling. We will specifically describe the USCs characteristics, in addition to their differentiation potential. Then, we will introduce and explore the primary uses of USCs. These involve thier utilization as a platform to produce stem cells, however, we shall concentrate on the utilization of USCs for therapeutic, and regenerative orofacial applications, providing an in-depth evaluation of this purpose. The final portion will address the limitations and challenges of their implementation in regenerative dentistry.
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Affiliation(s)
- Gamal A Atia
- Department of Oral Medicine, Periodontology, and Diagnosis, Faculty of Dentistry, Suez Canal University, Ismailia 41522, Egypt.
| | - Fatema Rashed
- Department of Basic Medical and Dental Sciences, Faculty of Dentistry, Zarqa University, Zarqa 13110, Jordan
| | - Ehab S Taher
- Department of Basic Medical and Dental Sciences, Faculty of Dentistry, Zarqa University, Zarqa 13110, Jordan
| | - Ssang-Goo Cho
- Department of Stem Cell and Regenerative Biotechnology and Institute of Advanced Regenerative Science, Konkuk University, Seoul 05029, South Korea.
| | - Ahmed Abdal Dayem
- Department of Stem Cell and Regenerative Biotechnology and Institute of Advanced Regenerative Science, Konkuk University, Seoul 05029, South Korea
| | - Magdalen M Soliman
- Department of Oral Medicine, Periodontology, and Diagnosis, Faculty of Dentistry, Badr University, Egypt
| | - Hany K Shalaby
- Department of Oral Medicine, Periodontology and Oral Diagnosis, Faculty of Dentistry, Suez University, Suez 43512, Egypt
| | - Nourelhuda A Mohammed
- Physiology and Biochemistry Department, Faculty of Medicine, Mutah University, Mutah, Al-Karak 61710, Jordan
| | - Noha Taymour
- Department of Substitutive Dental Sciences, College of Dentistry, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia
| | - Mohamed El-Sherbiny
- Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, 71666, Riyadh 11597, Saudi Arabia; Department of Anatomy, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt
| | - Elturabi Ebrahim
- Department of Medical Surgical Nursing, Nursing College, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
| | - Mahmoud M Ramadan
- Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates
| | - Afaf Abdelkader
- Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Benha University, Benha 13518, Egypt
| | - Mohamed Abdo
- Department of Animal Histology and Anatomy, School of Veterinary Medicine, Badr University in Cairo (BUC), Badr City, Egypt; Department of Anatomy and Embryology, Faculty Veterinary Medicine, University of Sadat City, Sadat City, Egypt
| | - Ahmed A Aldarmahi
- Department of Basic Science, College of Science and Health Professions, King Saud bin Abdulaziz University for Health Sciences, Jeddah 21582, Saudi Arabia; National Guard, Health Affairs, King Abdullah International Medical Research Centre, Jeddah 21582, Saudi Arabia
| | - Ahmed M Atwa
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Egyptian Russian University, Cairo 11829, Egypt
| | - Duaa A Bafail
- Department of Clinical Pharmacology, Faculty of Medicine, King Abdulaziz University, Jeddah 11829, Saudi Arabia
| | - Ahmed Abdeen
- Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Benha University, Toukh 13736, Egypt.
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Sun Y, Zhao H, Yang S, Wang G, Zhu L, Sun C, An Y. Urine-derived stem cells: Promising advancements and applications in regenerative medicine and beyond. Heliyon 2024; 10:e27306. [PMID: 38509987 PMCID: PMC10951541 DOI: 10.1016/j.heliyon.2024.e27306] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2023] [Revised: 02/27/2024] [Accepted: 02/27/2024] [Indexed: 03/22/2024] Open
Abstract
Currently, stem cells are a prominent focus of regenerative engineering research. However, due to the limitations of commonly used stem cell sources, their application in therapy is often restricted to the experimental stage and constrained by ethical considerations. In contrast, urine-derived stem cells (USCs) offer promising advantages for clinical trials and applications. The noninvasive nature of the collection process allows for repeated retrieval within a short period, making it a more feasible option. Moreover, studies have shown that USCs have a protective effect on organs, promoting vascular regeneration, inhibiting oxidative stress, and reducing inflammation in various acute and chronic organ dysfunctions. The application of USCs has also been enhanced by advancements in biomaterials technology, enabling better targeting and controlled release capabilities. This review aims to summarize the current state of research on USCs, providing insights for future applications in basic and clinical settings.
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Affiliation(s)
| | | | - Shuguang Yang
- Department of Critical Care Medicine, Peking University People's Hospital, PR China
| | - Guangjie Wang
- Department of Critical Care Medicine, Peking University People's Hospital, PR China
| | - Leijie Zhu
- Department of Critical Care Medicine, Peking University People's Hospital, PR China
| | - Chang Sun
- Department of Critical Care Medicine, Peking University People's Hospital, PR China
| | - Youzhong An
- Department of Critical Care Medicine, Peking University People's Hospital, PR China
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Kunitake K, Motohashi N, Inoue T, Suzuki Y, Aoki Y. Characterization of CD90/Thy-1 as a crucial molecular signature for myogenic differentiation in human urine-derived cells through single-cell RNA sequencing. Sci Rep 2024; 14:2329. [PMID: 38282008 PMCID: PMC10822841 DOI: 10.1038/s41598-024-52530-5] [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: 06/16/2023] [Accepted: 01/19/2024] [Indexed: 01/30/2024] Open
Abstract
Human urine-derived cells (UDCs) are primary cultured cells originating from the upper urinary tract and are known to be multipotent. We previously developed MYOD1-transduced UDCs (MYOD1-UDCs) as a model recapitulating the pathogenesis of Duchenne muscular dystrophy (DMD) caused by a lack of dystrophin. MYOD1-UDCs also allow evaluation of the efficacy of exon skipping with antisense oligonucleotides. However, despite the introduction of MYOD1, some MYOD1-UDCs failed to form myotubes, possibly because of heterogeneity among UDCs. Here, we carried out single-cell RNA-sequencing analyses and revealed that CD90/Thy-1 was highly expressed in a limited subpopulation of UDCs with high myogenic potency. Furthermore, CD90-positive MYOD1-UDCs, but not CD90-negative cells, could form myotubes expressing high levels of myosin heavy chain and dystrophin. Notably, overexpression of CD90 in CD90-negative MYOD1-UDCs did not enhance myogenic differentiation, whereas CD90 suppression in CD90-positive UDCs led to decreased myotube formation and decreased myosin heavy chain expression. CD90 may thus contribute to the fusion of single-nucleated MYOD1-UDCs into myotubes but is not crucial for promoting the expression of late muscle regulatory factors. Finally, we confirmed that CD90-positive MYOD1-UDCs derived from patients with DMD were a valuable tool for obtaining a highly reproducible and stable evaluation of exon skipping using antisense oligonucleotide.
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Affiliation(s)
- Katsuhiko Kunitake
- Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), 4-1-1 Ogawa-Higashi, Kodaira, Tokyo, 187-8502, Japan
- Department of NCNP Brain Physiology and Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
| | - Norio Motohashi
- Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), 4-1-1 Ogawa-Higashi, Kodaira, Tokyo, 187-8502, Japan
| | - Takafumi Inoue
- Department of Life Science and Medical Bioscience, Waseda University, Tokyo, Japan
| | - Yutaka Suzuki
- Laboratory of Systems Genomics, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan
| | - Yoshitsugu Aoki
- Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), 4-1-1 Ogawa-Higashi, Kodaira, Tokyo, 187-8502, Japan.
- Department of NCNP Brain Physiology and Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
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Cavaleiro C, Afonso GJM, Oliveira PJ, Valero J, Mota SI, Ferreiro E. Urine-derived stem cells in neurological diseases: current state-of-the-art and future directions. Front Mol Neurosci 2023; 16:1229728. [PMID: 37965041 PMCID: PMC10642248 DOI: 10.3389/fnmol.2023.1229728] [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: 05/26/2023] [Accepted: 10/10/2023] [Indexed: 11/16/2023] Open
Abstract
Stem cells have potential applications in the field of neurological diseases, as they allow for the development of new biological models. These models can improve our understanding of the underlying pathologies and facilitate the screening of new therapeutics in the context of precision medicine. Stem cells have also been applied in clinical tests to repair tissues and improve functional recovery. Nevertheless, although promising, commonly used stem cells display some limitations that curb the scope of their applications, such as the difficulty of obtention. In that regard, urine-derived cells can be reprogrammed into induced pluripotent stem cells (iPSCs). However, their obtaining can be challenging due to the low yield and complexity of the multi-phased and typically expensive differentiation protocols. As an alternative, urine-derived stem cells (UDSCs), included within the population of urine-derived cells, present a mesenchymal-like phenotype and have shown promising properties for similar purposes. Importantly, UDSCs have been differentiated into neuronal-like cells, auspicious for disease modeling, while overcoming some of the shortcomings presented by other stem cells for these purposes. Thus, this review assesses the current state and future perspectives regarding the potential of UDSCs in the ambit of neurological diseases, both for disease modeling and therapeutic applications.
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Affiliation(s)
- Carla Cavaleiro
- CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal
- Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal
- Institute for Interdisciplinary Research, University of Coimbra, Doctoral Programme in Experimental Biology and Biomedicine (PDBEB), Coimbra, Portugal
| | - Gonçalo J. M. Afonso
- CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal
- Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal
- Institute for Interdisciplinary Research, University of Coimbra, Doctoral Programme in Experimental Biology and Biomedicine (PDBEB), Coimbra, Portugal
| | - Paulo J. Oliveira
- CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal
- Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal
| | - Jorge Valero
- Instituto de Neurociencias de Castilla y León, University of Salamanca, Salamanca, Spain
- Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain
- Department of Cell Biology and Pathology, University of Salamanca, Salamanca, Spain
| | - Sandra I. Mota
- CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal
- Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal
| | - Elisabete Ferreiro
- CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal
- Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal
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Dvorakova J, Wiesnerova L, Chocholata P, Kulda V, Landsmann L, Cedikova M, Kripnerova M, Eberlova L, Babuska V. Human cells with osteogenic potential in bone tissue research. Biomed Eng Online 2023; 22:33. [PMID: 37013601 PMCID: PMC10069154 DOI: 10.1186/s12938-023-01096-w] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Accepted: 03/24/2023] [Indexed: 04/05/2023] Open
Abstract
Bone regeneration after injury or after surgical bone removal due to disease is a serious medical challenge. A variety of materials are being tested to replace a missing bone or tooth. Regeneration requires cells capable of proliferation and differentiation in bone tissue. Although there are many possible human cell types available for use as a model for each phase of this process, no cell type is ideal for each phase. Osteosarcoma cells are preferred for initial adhesion assays due to their easy cultivation and fast proliferation, but they are not suitable for subsequent differentiation testing due to their cancer origin and genetic differences from normal bone tissue. Mesenchymal stem cells are more suitable for biocompatibility testing, because they mimic natural conditions in healthy bone, but they proliferate more slowly, soon undergo senescence, and some subpopulations may exhibit weak osteodifferentiation. Primary human osteoblasts provide relevant results in evaluating the effect of biomaterials on cellular activity; however, their resources are limited for the same reasons, like for mesenchymal stem cells. This review article provides an overview of cell models for biocompatibility testing of materials used in bone tissue research.
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Affiliation(s)
- Jana Dvorakova
- Department of Medical Chemistry and Biochemistry, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1655/76, 323 00, Plzen, Czech Republic
| | - Lucie Wiesnerova
- Department of Medical Chemistry and Biochemistry, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1655/76, 323 00, Plzen, Czech Republic
| | - Petra Chocholata
- Department of Medical Chemistry and Biochemistry, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1655/76, 323 00, Plzen, Czech Republic
| | - Vlastimil Kulda
- Department of Medical Chemistry and Biochemistry, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1655/76, 323 00, Plzen, Czech Republic
| | - Lukas Landsmann
- Department of Medical Chemistry and Biochemistry, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1655/76, 323 00, Plzen, Czech Republic
| | - Miroslava Cedikova
- Biomedical Center, Laboratory of Tumor Biology and Immunotherapy, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1655/76, 323 00, Plzen, Czech Republic
| | - Michaela Kripnerova
- Department of Biology, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1655/76, 323 00, Plzen, Czech Republic
| | - Lada Eberlova
- Department of Anatomy, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1655/76, 323 00, Plzen, Czech Republic
| | - Vaclav Babuska
- Department of Medical Chemistry and Biochemistry, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1655/76, 323 00, Plzen, Czech Republic.
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10
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Qin L, Liu N, Bao CLM, Yang DZ, Ma GX, Yi WH, Xiao GZ, Cao HL. Mesenchymal stem cells in fibrotic diseases-the two sides of the same coin. Acta Pharmacol Sin 2023; 44:268-287. [PMID: 35896695 PMCID: PMC9326421 DOI: 10.1038/s41401-022-00952-0] [Citation(s) in RCA: 44] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2022] [Accepted: 06/29/2022] [Indexed: 02/06/2023] Open
Abstract
Fibrosis is caused by extensive deposition of extracellular matrix (ECM) components, which play a crucial role in injury repair. Fibrosis attributes to ~45% of all deaths worldwide. The molecular pathology of different fibrotic diseases varies, and a number of bioactive factors are involved in the pathogenic process. Mesenchymal stem cells (MSCs) are a type of multipotent stem cells that have promising therapeutic effects in the treatment of different diseases. Current updates of fibrotic pathogenesis reveal that residential MSCs may differentiate into myofibroblasts which lead to the fibrosis development. However, preclinical and clinical trials with autologous or allogeneic MSCs infusion demonstrate that MSCs can relieve the fibrotic diseases by modulating inflammation, regenerating damaged tissues, remodeling the ECMs, and modulating the death of stressed cells after implantation. A variety of animal models were developed to study the mechanisms behind different fibrotic tissues and test the preclinical efficacy of MSC therapy in these diseases. Furthermore, MSCs have been used for treating liver cirrhosis and pulmonary fibrosis patients in several clinical trials, leading to satisfactory clinical efficacy without severe adverse events. This review discusses the two opposite roles of residential MSCs and external MSCs in fibrotic diseases, and summarizes the current perspective of therapeutic mechanism of MSCs in fibrosis, through both laboratory study and clinical trials.
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Affiliation(s)
- Lei Qin
- grid.33199.310000 0004 0368 7223Department of Orthopedics, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, 518000 China
| | - Nian Liu
- grid.33199.310000 0004 0368 7223Department of Orthopedics, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, 518000 China
| | - Chao-le-meng Bao
- CASTD Regengeek (Shenzhen) Medical Technology Co. Ltd, Shenzhen, 518000 China
| | - Da-zhi Yang
- grid.33199.310000 0004 0368 7223Department of Orthopedics, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, 518000 China
| | - Gui-xing Ma
- grid.263817.90000 0004 1773 1790Department of Biochemistry, School of Medicine, Southern University of Science and Technology, Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Shenzhen Key Laboratory of Cell Microenvironment, Shenzhen, 518055 China
| | - Wei-hong Yi
- grid.33199.310000 0004 0368 7223Department of Orthopedics, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, 518000 China
| | - Guo-zhi Xiao
- grid.263817.90000 0004 1773 1790Department of Biochemistry, School of Medicine, Southern University of Science and Technology, Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Shenzhen Key Laboratory of Cell Microenvironment, Shenzhen, 518055 China
| | - Hui-ling Cao
- grid.263817.90000 0004 1773 1790Department of Biochemistry, School of Medicine, Southern University of Science and Technology, Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Shenzhen Key Laboratory of Cell Microenvironment, Shenzhen, 518055 China
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11
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You Q, Lu M, Li Z, Zhou Y, Tu C. Cell Sheet Technology as an Engineering-Based Approach to Bone Regeneration. Int J Nanomedicine 2022; 17:6491-6511. [PMID: 36573205 PMCID: PMC9789707 DOI: 10.2147/ijn.s382115] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Accepted: 11/12/2022] [Indexed: 12/24/2022] Open
Abstract
Bone defects that are congenital or the result of infection, malignancy, or trauma represent a challenge to the global healthcare system. To address this issue, multiple research groups have been developing novel cell sheet technology (CST)-based approaches to promote bone regeneration. These methods hold promise for use in regenerative medicine because they preserve cell-cell contacts, cell-extracellular matrix interactions, and the protein makeup of cell membranes. This review introduces the concept and preparation system of the cell sheet (CS), explores the application of CST in bone regeneration, highlights the current states of the bone regeneration via CST, and offers perspectives on the challenges and future research direction of translating current knowledge from the lab to the clinic.
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Affiliation(s)
- Qi You
- Orthopedic Research Institute, Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China,Sichuan Model Worker and Craftsman Talent Innovation Research Studio, Chengdu, Sichuan Province, People’s Republic of China
| | - Minxun Lu
- Orthopedic Research Institute, Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China,Sichuan Model Worker and Craftsman Talent Innovation Research Studio, Chengdu, Sichuan Province, People’s Republic of China
| | - Zhuangzhuang Li
- Orthopedic Research Institute, Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China,Sichuan Model Worker and Craftsman Talent Innovation Research Studio, Chengdu, Sichuan Province, People’s Republic of China
| | - Yong Zhou
- Orthopedic Research Institute, Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China,Sichuan Model Worker and Craftsman Talent Innovation Research Studio, Chengdu, Sichuan Province, People’s Republic of China
| | - Chongqi Tu
- Orthopedic Research Institute, Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China,Sichuan Model Worker and Craftsman Talent Innovation Research Studio, Chengdu, Sichuan Province, People’s Republic of China,Correspondence: Chongqi Tu; Yong Zhou, Department of Orthopedics, West China Hospital, Sichuan University, No. 37, Guoxuexiang, Chengdu, 610041, Sichuan Province, People’s Republic of China, Email ;
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12
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Urine-Derived Stem Cells for Epithelial Tissues Reconstruction and Wound Healing. Pharmaceutics 2022; 14:pharmaceutics14081669. [PMID: 36015295 PMCID: PMC9415563 DOI: 10.3390/pharmaceutics14081669] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Revised: 08/09/2022] [Accepted: 08/09/2022] [Indexed: 11/17/2022] Open
Abstract
Epithelial tissue injury can occur on any surface site of the body, particularly in the skin or urethral mucosa tissue, due to trauma, infection, inflammation, and toxic compounds. Both internal and external body epithelial tissue injuries can significantly affect patients’ quality of life, increase healthcare spending, and increase the global economic burden. Transplantation of epithelial tissue grafts is an effective treatment strategy in clinical settings. Autologous bio-engineered epithelia are common clinical skin substitutes that have the specific advantages of avoiding tissue rejection, obviating ethical concerns, reducing the risk of infection, and decreasing scarring compared to donor grafts. However, epithelial cells are often obtained from the individual’s skin and mucosa through invasive methods, which cause further injury or damage. Urine-derived stem cells (USC) of kidney origin, obtained via non-invasive acquisition, possess high stemness properties, self-renewal ability, trophic effects, multipotent differentiation potential, and immunomodulatory ability. These cells show versatile potential for tissue regeneration, with extensive evidence supporting their use in the repair of epidermal and urothelial injuries. We discuss the collection, isolation, culture, characterization, and differentiation of USC. We also discuss the use of USC for cellular therapies as well as the administration of USC-derived paracrine factors for epidermal and urothelial tissue repair. Specifically, we will discuss 3D constructions involving multiple types of USC-loaded hydrogels and USC-seeded scaffolds for use in cosmetic production testing, drug development, and disease modeling. In conclusion, urine-derived stem cells are a readily accessible autologous stem cell source well-suited for developing personalized medical treatments in epithelial tissue regeneration and drug testing.
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Huang YZ, He T, Cui J, Jiang YL, Zeng JF, Zhang WQ, Xie HQ. Urine-Derived Stem Cells for Regenerative Medicine: Basic Biology, Applications, and Challenges. TISSUE ENGINEERING. PART B, REVIEWS 2022; 28:978-994. [PMID: 35049395 DOI: 10.1089/ten.teb.2021.0142] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Regenerative medicine based on stem cell research has the potential to provide advanced health care for human beings. Recent studies demonstrate that stem cells in human urine can serve as an excellent source of graft cells for regenerative therapy, mainly due to simple, low-cost, and noninvasive cell isolation. These cells, termed human urine-derived stem cells (USCs), are highly expandable and can differentiate into various cell lineages. They share many biological properties with mesenchymal stem cells, such as potent paracrine effects and immunomodulation ability. The advantage of USCs has motivated researchers to explore their applications in regenerative medicine, including genitourinary regeneration, musculoskeletal repair, skin wound healing, and disease treatment. Although USCs have showed many positive outcomes in preclinical studies, and although the possible applications of USCs for animal therapy have been reported, many issues need to be addressed before clinical translation. This article provides a comprehensive review of USC biology and recent advances in their application for tissue regeneration. Challenges in the clinical translation of USC-based therapy are also discussed. Impact statement Recently, stem cells isolated from urine, referred to as urine-derived stem cells (USCs), have gained much interest in the field of regenerative medicine. Many advantages of human USCs have been found for cell-based therapy: (i) the cell isolation procedure is simple and low cost; (ii) they have remarkable proliferation ability, multidifferentiation potential, and paracrine effects; and (iii) they facilitate tissue regeneration in many animal models. With the hope to facilitate the development of USC-based therapy, we describe the current understanding of USC biology, summarize recent advances in their applications, and discuss future challenges in clinical translation.
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Affiliation(s)
- Yi-Zhou Huang
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
| | - Tao He
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China.,Department of Breast Surgery, West China School of Medicine/West China Hospital, Sichuan University, Chengdu, China
| | - Jing Cui
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
| | - Yan-Lin Jiang
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
| | - Jun-Feng Zeng
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
| | - Wen-Qian Zhang
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
| | - Hui-Qi Xie
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
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14
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Falzarano MS, Grilli A, Zia S, Fang M, Rossi R, Gualandi F, Rimessi P, El Dani R, Fabris M, Lu Z, Li W, Mongini T, Ricci F, Pegoraro E, Bello L, Barp A, Sansone VA, Hegde M, Roda B, Reschiglian P, Bicciato S, Selvatici R, Ferlini A. RNA-seq in DMD urinary stem cells recognized muscle-related transcription signatures and addressed the identification of atypical mutations by whole-genome sequencing. HGG ADVANCES 2022; 3:100054. [PMID: 35047845 PMCID: PMC8756543 DOI: 10.1016/j.xhgg.2021.100054] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2021] [Accepted: 08/18/2021] [Indexed: 12/13/2022] Open
Abstract
Urinary stem cells (USCs) are a non-invasive, simple, and affordable cell source to study human diseases. Here we show that USCs are a versatile tool for studying Duchenne muscular dystrophy (DMD), since they are able to address RNA signatures and atypical mutation identification. Gene expression profiling of DMD individuals' USCs revealed a profound deregulation of inflammation, muscle development, and metabolic pathways that mirrors the known transcriptional landscape of DMD muscle and worsens following USCs' myogenic transformation. This pathogenic transcription signature was reverted by an exon-skipping corrective approach, suggesting the utility of USCs in monitoring DMD antisense therapy. The full DMD transcript profile performed in USCs from three undiagnosed DMD individuals addressed three splicing abnormalities, which were decrypted and confirmed as pathogenic variations by whole-genome sequencing (WGS). This combined genomic approach allowed the identification of three atypical and complex DMD mutations due to a deep intronic variation and two large inversions, respectively. All three mutations affect DMD gene splicing and cause a lack of dystrophin protein production, and one of these also generates unique fusion genes and transcripts. Further characterization of USCs using a novel cell-sorting technology (Celector) highlighted cell-type variability and the representation of cell-specific DMD isoforms. Our comprehensive approach to USCs unraveled RNA, DNA, and cell-specific features and demonstrated that USCs are a robust tool for studying and diagnosing DMD.
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Affiliation(s)
- Maria S Falzarano
- Department of Medical Sciences, Unit of Medical Genetics, University of Ferrara, Ferrara 44121, Italy
| | - Andrea Grilli
- Department of Life Sciences, University of Modena and Reggio Emilia, Modena 41121, Italy
| | | | | | - Rachele Rossi
- Department of Medical Sciences, Unit of Medical Genetics, University of Ferrara, Ferrara 44121, Italy
| | - Francesca Gualandi
- Department of Medical Sciences, Unit of Medical Genetics, University of Ferrara, Ferrara 44121, Italy
| | - Paola Rimessi
- Department of Medical Sciences, Unit of Medical Genetics, University of Ferrara, Ferrara 44121, Italy
| | - Reem El Dani
- Department of Medical Sciences, Unit of Medical Genetics, University of Ferrara, Ferrara 44121, Italy
| | - Marina Fabris
- Department of Medical Sciences, Unit of Medical Genetics, University of Ferrara, Ferrara 44121, Italy
| | | | - Wenyan Li
- BGI-Shenzhen, Shenzhen 518083, China
| | | | | | - Elena Pegoraro
- ERN Neuromuscular Center, Department of Neurosciences, Unit of Neurology, University of Padua, Padua 35122, Italy
| | - Luca Bello
- ERN Neuromuscular Center, Department of Neurosciences, Unit of Neurology, University of Padua, Padua 35122, Italy
| | - Andrea Barp
- The NEMO Clinical Center, Neurorehabilitation Unit, University of Milan, Milan 20162, Italy
| | - Valeria A Sansone
- The NEMO Clinical Center, Neurorehabilitation Unit, University of Milan, Milan 20162, Italy
| | - Madhuri Hegde
- PerkinElmer Genomics, 3950 Shackleford Rd., Ste. 195, Duluth, GA 30096, USA
| | - Barbara Roda
- Stem Sel s.r.l., Bologna 40127, Italy
- Department of Chemistry "G. Ciamician," University of Bologna, Bologna 40126, Italy
| | - Pierluigi Reschiglian
- Stem Sel s.r.l., Bologna 40127, Italy
- Department of Chemistry "G. Ciamician," University of Bologna, Bologna 40126, Italy
| | - Silvio Bicciato
- Department of Life Sciences, University of Modena and Reggio Emilia, Modena 41121, Italy
| | - Rita Selvatici
- Department of Medical Sciences, Unit of Medical Genetics, University of Ferrara, Ferrara 44121, Italy
| | - Alessandra Ferlini
- Department of Medical Sciences, Unit of Medical Genetics, University of Ferrara, Ferrara 44121, Italy
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15
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Zhang W, Hu J, Huang Y, Wu C, Xie H. Urine-derived stem cells: applications in skin, bone and articular cartilage repair. BURNS & TRAUMA 2021; 9:tkab039. [PMID: 34859109 PMCID: PMC8633594 DOI: 10.1093/burnst/tkab039] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Revised: 09/18/2021] [Indexed: 02/05/2023]
Abstract
As an emerging type of adult stem cell featuring non-invasive acquisition, urine-derived stem cells (USCs) have shown great potential for applications in tissue engineering and regenerative medicine. With a growing amount of research on the topic, the effectiveness of USCs in various disease models has been shown and the underlying mechanisms have also been explored, though many aspects still remain unclear. In this review, we aim to provide an up-to-date overview of the biological characteristics of USCs and their applications in skin, bone and articular cartilage repair. In addition to the identification procedure of USCs, we also summarize current knowledge of the underlying repair mechanisms and application modes of USCs. Potential concerns and perspectives have also been summarized.
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Affiliation(s)
- Wenqian Zhang
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, Med-X Center for Materials, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Jungen Hu
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, Med-X Center for Materials, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Yizhou Huang
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, Med-X Center for Materials, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Chenyu Wu
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, Med-X Center for Materials, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Huiqi Xie
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, Med-X Center for Materials, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
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16
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Li H, Fan XL, Wang YN, Lu W, Wang H, Liao R, Zeng M, Yang JX, Hu Y, Xie J. Extracellular Vesicles from Human Urine-Derived Stem Cells Ameliorate Particulate Polyethylene-Induced Osteolysis. Int J Nanomedicine 2021; 16:7479-7494. [PMID: 34785895 PMCID: PMC8579861 DOI: 10.2147/ijn.s325646] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Accepted: 10/04/2021] [Indexed: 01/27/2023] Open
Abstract
Purpose Wear debris particle-induced periprosthetic osteolysis is a severe complication of total joint replacement that results in aseptic loosening and subsequent arthroplasty failure. No effective therapeutic agents or drugs have been approved to prevent or treat osteolysis; thus, revision surgery is often needed. Extracellular vesicles (EVs) are vital nanosized regulators of intercellular communication that can be directly applied to promote tissue repair and regeneration. In this study, we assessed the therapeutic potential of EVs from human urine-derived stem cells (USCs) (USC-EVs) in preventing ultrahigh-molecular-weight polyethylene (UHMWPE) particle-induced osteolysis. Methods USCs were characterized by measuring induced multipotent differentiation and flow cytometry. USC-EVs were isolated and characterized using transmission electron microscopy (TEM), dynamic light scattering (DLS) and Western blotting. RAW264.7 cells and bone marrow mesenchymal stem cells (BMSCs) were cultured with USC-EVs to verify osteoclast differentiation and osteoblast formation, respectively, in vitro. The effects of USC-EVs were investigated on a UHMWPE particle-induced murine calvarial osteolysis model by assessing bone mass, the inflammatory reaction, and osteoblast and osteoclast formation. Results USCs differentiated into osteogenic, adipogenic and chondrogenic cells in vitro and were positive for CD44, CD73, CD29 and CD90 but negative for CD34 and CD45. USC-EVs exhibited a cup-like morphology with a double-layered membrane structure and were positive for CD63 and TSG101 and negative for calnexin. In vitro, USC-EVs promoted the osteogenic differentiation of BMSCs and reduced proinflammatory factor production and osteoclastic activity in RAW264.7 cells. In vivo, local injection of USC-EVs around the central sites of the calvaria decreased inflammatory cytokine generation and osteolysis compared with the control groups and significantly increased bone formation. Conclusion Based on our findings, USC-EVs prevent UHMWPE particle-induced osteolysis by decreasing inflammation, suppressing bone resorption and promoting bone formation.
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Affiliation(s)
- Hui Li
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.,Hunan Engineering Research Center of Biomedical Metal and Ceramic Implants, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China
| | - Xiao-Lei Fan
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.,Hunan Engineering Research Center of Biomedical Metal and Ceramic Implants, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China
| | - Yi-Nan Wang
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.,Hunan Engineering Research Center of Biomedical Metal and Ceramic Implants, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China
| | - Wei Lu
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.,Hunan Engineering Research Center of Biomedical Metal and Ceramic Implants, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China
| | - Haoyi Wang
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.,Hunan Engineering Research Center of Biomedical Metal and Ceramic Implants, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China
| | - Runzhi Liao
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.,Hunan Engineering Research Center of Biomedical Metal and Ceramic Implants, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China
| | - Min Zeng
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.,Hunan Engineering Research Center of Biomedical Metal and Ceramic Implants, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China
| | - Jun-Xiao Yang
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.,Hunan Engineering Research Center of Biomedical Metal and Ceramic Implants, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China
| | - Yihe Hu
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.,Hunan Engineering Research Center of Biomedical Metal and Ceramic Implants, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China
| | - Jie Xie
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.,Hunan Engineering Research Center of Biomedical Metal and Ceramic Implants, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China
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17
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Cell preservation methods and its application to studying rare disease. Mol Cell Probes 2021; 56:101694. [PMID: 33429040 DOI: 10.1016/j.mcp.2021.101694] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Revised: 12/21/2020] [Accepted: 01/05/2021] [Indexed: 12/30/2022]
Abstract
The ability to preserve and transport human cells in a stable medium over long distances is critical to collaborative efforts and the advancement of knowledge in the study of human disease. This is particularly important in the study of rare diseases. Recently, advancements in the understanding of renal ciliopathies has been achieved via the use of patient urine-derived cells (UDCs). However, the traditional method of cryopreservation, although considered as the gold standard, can result in decreased sample viability of many cell types, including UDCs. Delays in transportation can have devastating effects upon the viability of samples, and may even result in complete destruction of cells following evaporation of dry ice or liquid nitrogen, leaving samples in cryoprotective agents, which are cytotoxic at room temperature. The loss of any patient sample in this manner is detrimental to research, however it is even more so when samples are from patients with a rare disease. In order to overcome the associated limitations of traditional practices, new methods of preservation and shipment, including cell encapsulation within hydrogels, and transport in specialised devices are continually being investigated. Here we summarise and compare traditional methods with emerging novel alternatives for the preservation and shipment of cells, and consider the effectiveness of such methods for use with UDCs to further enable the study and understanding of kidney diseases.
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18
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Burdeyron P, Giraud S, Hauet T, Steichen C. Urine-derived stem/progenitor cells: A focus on their characterization and potential. World J Stem Cells 2020; 12:1080-1096. [PMID: 33178393 PMCID: PMC7596444 DOI: 10.4252/wjsc.v12.i10.1080] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Revised: 06/26/2020] [Accepted: 08/24/2020] [Indexed: 02/06/2023] Open
Abstract
Cell therapy, i.e., the use of cells to repair an affected tissue or organ, is at the forefront of regenerative and personalized medicine. Among the multiple cell types that have been used for this purpose [including adult stem cells such as mesenchymal stem cells or pluripotent stem cells], urine-derived stem cells (USCs) have aroused interest in the past years. USCs display classical features of mesenchymal stem cells such as differentiation capacity and immunomodulation. Importantly, they have the main advantage of being isolable from one sample of voided urine with a cheap and unpainful procedure, which is broadly applicable, whereas most adult stem cell types require invasive procedure. Moreover, USCs can be differentiated into renal cell types. This is of high interest for renal cell therapy-based regenerative approaches. This review will firstly describe the isolation and characterization of USCs. We will specifically present USC phenotype, which is not an object of consensus in the literature, as well as detail their differentiation capacity. In the second part of this review, we will present and discuss the main applications of USCs. These include use as a substrate to generate human induced pluripotent stem cells, but we will deeply focus on the use of USCs for cell therapy approaches with a detailed analysis depending on the targeted organ or system. Importantly, we will also focus on the applications that rely on the use of USC-derived products such as microvesicles including exosomes, which is a strategy being increasingly employed. In the last section, we will discuss the remaining barriers and challenges in the field of USC-based regenerative medicine.
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Affiliation(s)
- Perrine Burdeyron
- INSERM U1082 IRTOMIT, CHU de Poitiers, Poitiers 86021, France
- Faculté de Médecine et Pharmacie, Université de Poitiers, Poitiers 86021, France
| | - Sébastien Giraud
- INSERM U1082 IRTOMIT, CHU de Poitiers, Poitiers 86021, France
- Service de Biochimie, CHU de Poitiers, Poitiers 86021, France
| | - Thierry Hauet
- INSERM U1082 IRTOMIT, CHU de Poitiers, Poitiers 86021, France
- Faculté de Médecine et Pharmacie, Université de Poitiers, Poitiers 86021, France
- Service de Biochimie, CHU de Poitiers, Poitiers 86021, France
| | - Clara Steichen
- INSERM U1082 IRTOMIT, CHU de Poitiers, Poitiers 86021, France
- Faculté de Médecine et Pharmacie, Université de Poitiers, Poitiers 86021, France.
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19
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Lee EJ, Jain M, Alimperti S. Bone Microvasculature: Stimulus for Tissue Function and Regeneration. TISSUE ENGINEERING PART B-REVIEWS 2020; 27:313-329. [PMID: 32940150 DOI: 10.1089/ten.teb.2020.0154] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Bone is a highly vascularized organ, providing structural support to the body, and its development, regeneration, and remodeling depend on the microvascular homeostasis. Loss or impairment of vascular function can develop diseases, such as large bone defects, avascular necrosis, osteoporosis, osteoarthritis, and osteopetrosis. In this review, we summarize how vasculature controls bone development and homeostasis in normal and disease cases. A better understanding of this process will facilitate the development of novel disease treatments that promote bone regeneration and remodeling. Specifically, approaches based on tissue engineering components, such as stem cells and growth factors, have demonstrated the capacity to induce bone microvasculature regeneration and mineralization. This knowledge will have relevant clinical implications for the treatment of bone disorders by developing novel pharmaceutical approaches and bone grafts. Finally, the tissue engineering approaches incorporating vascular components may widely be applied to treat other organ diseases by enhancing their regeneration capacity. Impact statement Bone vasculature is imperative in the process of bone development, regeneration, and remodeling. Alterations or disruption of the bone vasculature leads to loss of bone homeostasis and the development of bone diseases. In this study, we review the role of vasculature on bone diseases and how vascular tissue engineering strategies, with a detailed emphasis on the role of stem cells and growth factors, will contribute to bone therapeutics.
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Affiliation(s)
- Eun-Jin Lee
- American Dental Association Science and Research Institute, Gaithersburg, Maryland, USA
| | - Mahim Jain
- Kennedy Krieger Institute, John Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Stella Alimperti
- American Dental Association Science and Research Institute, Gaithersburg, Maryland, USA
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20
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Gur S, Hellstrom WJ. Harnessing Stem Cell Potential for the Treatment of Erectile Function in Men with Diabetes Mellitus: From Preclinical/Clinical Perspectives to Penile Tissue Engineering. Curr Stem Cell Res Ther 2020; 15:308-320. [DOI: 10.2174/1574888x14666190828142045] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2019] [Revised: 07/10/2019] [Accepted: 08/06/2019] [Indexed: 12/20/2022]
Abstract
Background::
According to the World Health Organization, more than 150 million people
are diabetic, and this number will increase twofold by the year 2025. Diabetes-related complications
affect all body organ systems, including the penis. Diabetes-induced Erectile Dysfunction (ED) is
caused by neuropathy of the penile nerves and vasculopathy involving the smooth muscle and endothelium
of the corpus cavernosum.
Objective::
This study aims to present an overview of Stem Cell (SC) research in diabetic animal models
of ED, focusing on the function, signaling, and niches that have a prominent role in the regeneration
of cavernosal cells and penile tissues. We highlight common erectile pathologies caused by diabetes
and review relevant preclinical trials. We also discuss paracrine mechanisms of various SC therapies
involved in the repair of endothelial cells and cavernous nerves in these diabetic models.
Method::
A PubMed search was performed, with dates ranging from inception until Mar 31, 2019.
Results::
This review provides a comprehensive evaluation of the various strategies that have been
investigated for improving SC delivery methods, through preclinical literature and published clinical
trials regarding ED in men with diabetes. Various cell-type applications have benefited erectile function
in diabetic models of ED.
Conclusion::
This review examines the progress and remaining challenges in diabetes-related SC research
regarding ED. Moving forward, it is only with a combined effort of basic biology and translational
work that the potential of SC-based therapies in diabetes in ED can be realized.
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Affiliation(s)
- Serap Gur
- Department of Urology, Tulane University Health Sciences Center, New Orleans, LA, United States
| | - Wayne J.G. Hellstrom
- Department of Urology, Tulane University Health Sciences Center, New Orleans, LA, United States
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21
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Liu D, Rychkov G, Al-Hawwas M, Manaph NPA, Zhou F, Bobrovskaya L, Liao H, Zhou XF. Conversion of human urine-derived cells into neuron-like cells by small molecules. Mol Biol Rep 2020; 47:2713-2722. [PMID: 32185687 DOI: 10.1007/s11033-020-05370-1] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2019] [Accepted: 03/04/2020] [Indexed: 01/04/2023]
Abstract
Neural cell transplantation is an effective way for treatment of neurological diseases. However, the absence of transplantable human neurons remains a barrier for clinical therapies. Human urine-derived cells, namely renal cells and urine stem cells, have become a good source of cells for reprogramming or trans-differentiation research. Here, we show that human urine-derived cells can be partially converted into neuron-like cells by applying a cocktail of small molecules. Gene expression analysis has shown that these induced cells expressed some neuron-specific genes, and a proportion of the cells are GABAergic neurons. Moreover, whole-cell patch clamping recording has shown that some induced cells have neuron-specific voltage gated Na+ and K+ currents but have failed to generate Ca2+ currents and action potentials. Taken together, these results suggest that induced neuronal cells from human urine-derived cells may be useful for neurological disease modelling, drug screening and cell therapies.
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Affiliation(s)
- Donghui Liu
- School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, 5000, Australia
- Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, 24 Tongjiaxiang Street, Nanjing, 210009, China
| | - Grigori Rychkov
- Discipline of Medicine, School of Medicine, University of Adelaide, Adelaide, SA, 5000, Australia
- South Australian Health and Medical Research Institute (SAHMRI), Adelaide, SA, 5000, Australia
| | - Mohammed Al-Hawwas
- School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, 5000, Australia
| | | | - Fiona Zhou
- School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, 5000, Australia
- Discipline of Medicine, School of Medicine, University of Adelaide, Adelaide, SA, 5000, Australia
- South Australian Health and Medical Research Institute (SAHMRI), Adelaide, SA, 5000, Australia
| | - Larisa Bobrovskaya
- School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, 5000, Australia
| | - Hong Liao
- Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, 24 Tongjiaxiang Street, Nanjing, 210009, China.
| | - Xin-Fu Zhou
- School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, 5000, Australia.
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22
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Urine-Derived Stem Cells: Applications in Regenerative and Predictive Medicine. Cells 2020; 9:cells9030573. [PMID: 32121221 PMCID: PMC7140531 DOI: 10.3390/cells9030573] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2019] [Revised: 02/17/2020] [Accepted: 02/25/2020] [Indexed: 12/14/2022] Open
Abstract
Despite being a biological waste, human urine contains a small population of cells with self-renewal capacity and differentiation potential into several cell types. Being derived from the convoluted tubules of nephron, renal pelvis, ureters, bladder and urethra, urine-derived stem cells (UDSC) have a similar phenotype to mesenchymal stroma cells (MSC) and can be reprogrammed into iPSC (induced pluripotent stem cells). Having simple, safer, low-cost and noninvasive collection procedures, the interest in UDSC has been growing in the last decade. With great potential in regenerative medicine applications, UDSC can also be used as biological models for pharmacology and toxicology tests. This review describes UDSC biological characteristics and differentiation potential and their possible use, including the potential of UDSC-derived iPSC to be used in drug discovery and toxicology, as well as in regenerative medicine. Being a new cellular platform amenable to noninvasive collection for disease stratification and personalized therapy could be a future application for UDSC.
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Xu Y, Zhang T, Chen Y, Shi Q, Li M, Qin T, Hu J, Lu H, Liu J, Chen C. Isolation and Characterization of Multipotent Canine Urine-Derived Stem Cells. Stem Cells Int 2020; 2020:8894449. [PMID: 33061993 PMCID: PMC7545436 DOI: 10.1155/2020/8894449] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Revised: 08/20/2020] [Accepted: 08/28/2020] [Indexed: 12/11/2022] Open
Abstract
Current cell-based therapies on musculoskeletal tissue regeneration were mostly determined in rodent models. However, a direct translation of those promising cell-based therapies to humans exists a significant hurdle. For solving this problem, canine has been developed as a new large animal model to bridge the gap from rodents to humans. In this study, we reported the isolation and characterization of urine-derived stem cells (USCs) from mature healthy beagle dogs. The isolated cells showed fibroblast-like morphology and had good clonogenicity and proliferation. Meanwhile, these cells positively expressed multiple markers of MSCs (CD29, CD44, CD90, and CD73), but negatively expressed for hematopoietic antigens (CD11b, CD34, and CD45). Additionally, after induction culturing, the isolated cells can be differentiated into osteogenic, adipogenic, chondrogenic, and tenogenic lineages. The successful isolation and verification of USCs from canine were useful for studying cell-based therapies and developing new treatments for musculoskeletal injuries using the preclinical canine model.
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Affiliation(s)
- Yan Xu
- 1Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China 410008
- 2Hunan Engineering Research Center of Sports and Health, Changsha, China 410008
- 3Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, China 410008
- 4Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, China 410008
| | - Tao Zhang
- 1Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China 410008
- 2Hunan Engineering Research Center of Sports and Health, Changsha, China 410008
- 3Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, China 410008
- 4Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, China 410008
| | - Yang Chen
- 1Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China 410008
- 2Hunan Engineering Research Center of Sports and Health, Changsha, China 410008
- 3Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, China 410008
- 4Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, China 410008
| | - Qiang Shi
- 1Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China 410008
- 2Hunan Engineering Research Center of Sports and Health, Changsha, China 410008
- 3Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, China 410008
- 4Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, China 410008
| | - Muzhi Li
- 1Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China 410008
- 2Hunan Engineering Research Center of Sports and Health, Changsha, China 410008
- 3Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, China 410008
- 4Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, China 410008
| | - Tian Qin
- 1Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China 410008
- 2Hunan Engineering Research Center of Sports and Health, Changsha, China 410008
- 3Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, China 410008
- 5Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China 410008
| | - Jianzhong Hu
- 1Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China 410008
- 2Hunan Engineering Research Center of Sports and Health, Changsha, China 410008
- 3Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, China 410008
- 5Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China 410008
| | - Hongbin Lu
- 1Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China 410008
- 2Hunan Engineering Research Center of Sports and Health, Changsha, China 410008
- 3Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, China 410008
- 4Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, China 410008
| | - Jun Liu
- 6Department of Limbs (Foot and Hand) Microsurgery, Affiliated Chenzhou No.1 People's Hospital, Southern Medical University, Chenzhou, China 423000
| | - Can Chen
- 1Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China 410008
- 2Hunan Engineering Research Center of Sports and Health, Changsha, China 410008
- 3Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, China 410008
- 7Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, China 410008
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Sato M, Takizawa H, Nakamura A, Turner BJ, Shabanpoor F, Aoki Y. Application of Urine-Derived Stem Cells to Cellular Modeling in Neuromuscular and Neurodegenerative Diseases. Front Mol Neurosci 2019; 12:297. [PMID: 31920531 PMCID: PMC6915080 DOI: 10.3389/fnmol.2019.00297] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2019] [Accepted: 11/20/2019] [Indexed: 12/11/2022] Open
Abstract
Neuromuscular and neurodegenerative diseases are mostly modeled using genetically modified animals such as mice. However, animal models do not recapitulate all the phenotypes that are specific to human disease. This is mainly due to the genetic, anatomical and physiological difference in the neuromuscular systems of animals and humans. The emergence of direct and indirect human somatic cell reprogramming technologies may overcome this limitation because they enable the use of disease and patient-specific cellular models as enhanced platforms for drug discovery and autologous cell-based therapy. Induced pluripotent stem cells (iPSCs) and urine-derived stem cells (USCs) are increasingly employed to recapitulate the pathophysiology of various human diseases. Recent cell-based modeling approaches utilize highly complex differentiation systems that faithfully mimic human tissue- and organ-level dysfunctions. In this review, we discuss promising cellular models, such as USC- and iPSC-based approaches, that are currently being used to model human neuromuscular and neurodegenerative diseases.
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Affiliation(s)
- Mitsuto Sato
- Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Japan.,Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine, Matsumoto, Japan
| | - Hotake Takizawa
- Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Japan
| | - Akinori Nakamura
- Department of Clinical Research, National Hospital Organization Matsumoto Medical Center, Matsumoto, Japan
| | - Bradley J Turner
- The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia
| | - Fazel Shabanpoor
- The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia
| | - Yoshitsugu Aoki
- Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Japan
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Sun X, Zheng W, Qian C, Wu Q, Hao Y, Lu G. Focal adhesion kinase promotes BMP2-induced osteogenic differentiation of human urinary stem cells via AMPK and Wnt signaling pathways. J Cell Physiol 2019; 235:4954-4964. [PMID: 31663128 DOI: 10.1002/jcp.29374] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2019] [Accepted: 09/27/2019] [Indexed: 12/18/2022]
Abstract
Human urine-derived stem cells (hUSCs) serve as favorable candidates for bone transplants due to their efficient proliferative and multipotent differentiation abilities, as well as the capacity to secrete a variety of vasoactive agents to facilitate tissue engineering. The present study aimed to explore the role of focal adhesion kinase (FAK) in bone morphogenetic protein 2 (BMP2)-induced osteogenic differentiation of hUSCs and to investigate the underlying mechanism. The degree of osteogenic differentiation and the correlated signals, following BMP2 overexpression and siRNA-mediated silencing of FAK, were determined in vitro. Moreover, hUSCs induced bone formation in a rat model with cranial defects, in vivo. Our findings revealed that alkaline phosphatase production, calcium deposits, osteocalcin and osteopontin expression, and bone formation were upregulated in vitro and in vivo following BMP2-induced osteogenic differentiation, and AMPK and Wnt signaling pathway activation by FAK could effectively regulate BMP2-enhanced osteogenic differentiation of hUSCs. Taken together, these findings indicated that FAK could mediate BMP2-enhanced osteogenic differentiation of hUSCs through activating adenosine 5'-monophosphate-activated protein kinase and Wnt signaling pathways.
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Affiliation(s)
- Xingwei Sun
- Department of Intervention, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Weiwei Zheng
- Department of Orthopaedics, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China
| | - Chen Qian
- Department of Orthopaedics, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China
| | - Qin Wu
- Department of Ultrasound, The Affiliated Suzhou Science & Technology Town Hospital of Nanjing Medical University, Suzhou, China
| | - Yuefeng Hao
- Department of Orthopaedics, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China
| | - Guohai Lu
- Department of Orthopaedics, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China
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Duan YR, Chen BP, Chen F, Yang SX, Zhu CY, Ma YL, Li Y, Shi J. Exosomal microRNA-16-5p from human urine-derived stem cells ameliorates diabetic nephropathy through protection of podocyte. J Cell Mol Med 2019; 25:10798-10813. [PMID: 31568645 PMCID: PMC8642687 DOI: 10.1111/jcmm.14558] [Citation(s) in RCA: 85] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2018] [Revised: 05/30/2019] [Accepted: 07/05/2019] [Indexed: 01/19/2023] Open
Abstract
Diabetic nephropathy (DN) remains one of the severe complications associated with diabetes mellitus. It is worthwhile to uncover the underlying mechanisms of clinical benefits of human urine‐derived stem cells (hUSCs) in the treatment of DN. At present, the clinical benefits associated with hUSCs in the treatment of DN remains unclear. Hence, our study aims to investigate protective effect of hUSC exosome along with microRNA‐16‐5p (miR‐16‐5p) on podocytes in DN via vascular endothelial growth factor A (VEGFA). Initially, miR‐16‐5p was predicated to target VEGFA based on data retrieved from several bioinformatics databases. Notably, dual‐luciferase report gene assay provided further verification confirming the prediction. Moreover, our results demonstrated that high glucose (HG) stimulation could inhibit miR‐16‐5p and promote VEGFA in human podocytes (HPDCs). miR‐16‐5p in hUSCs was transferred through the exosome pathway to HG‐treated HPDCs. The viability and apoptosis rate of podocytes after HG treatment together with expression of the related factors were subsequently determined. The results indicated that miR‐16‐5p secreted by hUSCs could improve podocyte injury induced by HG. In addition, VEGA silencing could also ameliorate HG‐induced podocyte injury. Finally, hUSC exosomes containing overexpressed miR‐16‐5p were injected into diabetic rats via tail vein, followed by qualification of miR‐16‐5p and observation on the changes of podocytes, which revealed that overexpressed miR‐16‐5p in hUSCs conferred protective effects on HPDCs in diabetic rats. Taken together, the present study revealed that overexpressed miR‐16‐5p in hUSC exosomes could protect HPDCs induced by HG and suppress VEGFA expression and podocytic apoptosis, providing fresh insights for novel treatment of DN.
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Affiliation(s)
- Yu-Rui Duan
- Department of Nephrology, Huaihe Hospital of Henan University, Kaifeng, China
| | - Bao-Ping Chen
- Department of Nephrology, Huaihe Hospital of Henan University, Kaifeng, China
| | - Fang Chen
- Department of Nephrology, Huaihe Hospital of Henan University, Kaifeng, China
| | - Su-Xia Yang
- Department of Nephrology, Huaihe Hospital of Henan University, Kaifeng, China
| | - Chao-Yang Zhu
- Department of Nephrology, Huaihe Hospital of Henan University, Kaifeng, China
| | - Ya-Li Ma
- Department of Nephrology, Huaihe Hospital of Henan University, Kaifeng, China
| | - Yang Li
- Department of Urology, Huaihe Hospital of Henan University, Kaifeng, China
| | - Jun Shi
- Department of Nephrology, Huaihe Hospital of Henan University, Kaifeng, China
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Identification and characterization of two morphologically distinct stem cell subpopulations from human urine samples. SCIENCE CHINA-LIFE SCIENCES 2019; 63:712-723. [PMID: 31515730 DOI: 10.1007/s11427-018-9543-1] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/05/2019] [Accepted: 05/06/2019] [Indexed: 02/05/2023]
Abstract
Urine-derived stem cells (USCs) have shown potentials for the treatment of skeletal and urological disorders. Based on published literature and our own data, USCs consist of heterogeneous populations of cells. In this paper, we identify and characterize two morphologically distinct subpopulations of USCs from human urine samples, named as spindle-shaped USCs (SS-USCs) and rice-shaped USCs (RS-USCs) respectively. The two subpopulations showed similar clone-forming efficiency, while SS-USCs featured faster proliferation, higher motility, and greater potential for osteogenic and adipogenic differentiation, RS-USCs showed greater potential for chondrogenic differentiation. POU5F1 was strongly expressed in both subpopulations, but MYC was weakly expressed. Both subpopulations showed similar patterns of CD24, CD29, CD34, CD44, CD73, CD90 and CD105 expression, while a higher percentage of RS-USCs were positive for CD133. SS-USCs were positive for VIM, weakly positive for SLC12A1 and UMOD, and negative for KRT18, NPHS1, AQP1 and AQP2, indicating a renal mesenchyme origin; while RS-USCs are positive for VIM, partially positive for KRT18, NPHS1, AQP1, SLC12A1 and UMOD, and negative for AQP2, indicating a nephron tubule origin. The above results can facilitate understanding of the biological characteristics of subpopulations of USCs, and provide a basis for further research and applications of such cells.
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Zhou M, Shen L, Qiao Y, Sun Z. Inducing differentiation of human urine-derived stem cells into hepatocyte-like cells by coculturing with human hepatocyte L02 cells. J Cell Biochem 2019; 121:566-573. [PMID: 31407401 DOI: 10.1002/jcb.29301] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2018] [Accepted: 06/27/2019] [Indexed: 12/11/2022]
Abstract
OBJECTIVES To investigate the possibility of inducing differentiation of human urine-derived stem cells (hUSCs) into hepatocyte-like cells by coculturing with human hepatocyte L02 cells in vitro. METHODS HUSCs were isolated from fresh urine samples collected from healthy adult volunteers by centrifugation. Cells were observed under an inverted phase contrast microscope, and proliferative activity was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Stem cell surface markers were detected by flow cytometry. HUSCs were induced to differentiate into hepatocyte-like cells by coculturing with human hepatocyte L02 cells, which were confirmed by cellular morphology, messenger RNA expression of albumin (ALB), α-fetoprotein (AFP) and hepatocyte cytochrome P450 (CYP450) analyzed with quantitative reverse transcription polymerase chain reaction and the expression of glycogen detected by glycogen staining kits at 5, 10, and 15 days after coculturing. RESULTS HUSCs from urine were successfully isolated and cultured in vitro. At passages 3, the growth curve of hUSCs was S-shaped with good proliferation activity. Mesenchymal stem cell surface markers CD44 and CD90 were detected positive by flow cytometry. CD31 for endothelial cells and CD34 for hematopoietic stem cell markers were not detected. HUSCs gained the cellular morphology and function of hepatocyte cells including higher expression of several hepatocyte-specific genes such as ALB and some CYP450, lower expression of AFP and positive glycogen expression (P < .05) in coculturing with human hepatocyte L02 cells for 10-15d. CONCLUSIONS HUSCs can be induced to differentiate into hepatocyte-like cells by coculturing with human hepatocyte L02 cells for a certain number of days.
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Affiliation(s)
- Ming Zhou
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
| | - Liangliang Shen
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
| | - Yinggu Qiao
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
| | - Zhenxiao Sun
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
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29
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Extracellular vesicles from human urine-derived stem cells prevent osteoporosis by transferring CTHRC1 and OPG. Bone Res 2019; 7:18. [PMID: 31263627 PMCID: PMC6594995 DOI: 10.1038/s41413-019-0056-9] [Citation(s) in RCA: 74] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2018] [Revised: 04/19/2019] [Accepted: 05/04/2019] [Indexed: 12/19/2022] Open
Abstract
Osteoporosis is a debilitating bone disease affecting millions of people. Here, we used human urine-derived stem cells (USCs), which were noninvasively harvested from unlimited and easily available urine, as a “factory” to obtain extracellular vesicles (USC-EVs) and demonstrated that the systemic injection of USC-EVs effectively alleviates bone loss and maintains bone strength in osteoporotic mice by enhancing osteoblastic bone formation and suppressing osteoclastic bone resorption. More importantly, the anti-osteoporotic properties of USC-EVs are not notably disrupted by the age, gender, or health condition (with or without osteoporosis) of the USC donor. Mechanistic studies determined that collagen triple-helix repeat containing 1 (CTHRC1) and osteoprotegerin (OPG) proteins are enriched in USC-EVs and required for USC-EV-induced pro-osteogenic and anti-osteoclastic effects. Our results suggest that autologous USC-EVs represent a promising novel therapeutic agent for osteoporosis by promoting osteogenesis and inhibiting osteoclastogenesis by transferring CTHRC1 and OPG.
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30
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Xing F, Liu G, Duan X, Xiang Z. [The application of urine derived stem cells in regeneration of musculoskeletal system]. ZHONGGUO XIU FU CHONG JIAN WAI KE ZA ZHI = ZHONGGUO XIUFU CHONGJIAN WAIKE ZAZHI = CHINESE JOURNAL OF REPARATIVE AND RECONSTRUCTIVE SURGERY 2018; 32:1477-1482. [PMID: 30417628 PMCID: PMC8414118 DOI: 10.7507/1002-1892.201804024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 04/08/2018] [Revised: 10/13/2018] [Indexed: 02/05/2023]
Abstract
Objective To review the application of urine derived stem cells (USCs) in regeneration of musculoskeletal system. Methods The original literature about USCs in the regeneration of musculoskeletal system was extensively reviewed and analyzed. Results The source of USCs is noninvasive and extensive. USCs express MSCs surface markers with stable proliferative and multi-directional differentiation capabilities, and are widely used in bone, skin, nerve, and other skeletal and muscle system regeneration fields and show a certain repair capacity. Conclusion USCs from non-invasive sources have a wide application prospect in the regeneration of musculoskeletal system, but the definite biological mechanism of its repair needs further study.
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Affiliation(s)
- Fei Xing
- Department of Orthopedics, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P.R.China
| | - Guoming Liu
- Department of Orthopedics, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P.R.China
| | - Xin Duan
- Department of Orthopedics, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P.R.China
| | - Zhou Xiang
- Department of Orthopedics, West China Hospital, Sichuan University, Chengdu Sichuan, 610041,
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Park H, Kim JS, Oh EJ, Kim TJ, Kim HM, Shim JH, Yoon WS, Huh JB, Moon SH, Kang SS, Chung HY. Effects of three-dimensionally printed polycaprolactone/β-tricalcium phosphate scaffold on osteogenic differentiation of adipose tissue- and bone marrow-derived stem cells. Arch Craniofac Surg 2018; 19:181-189. [PMID: 30282427 PMCID: PMC6177683 DOI: 10.7181/acfs.2018.01879] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2018] [Accepted: 09/10/2018] [Indexed: 11/11/2022] Open
Abstract
BACKGROUND Autogenous bone grafts have several limitations including donor-site problems and insufficient bone volume. To address these limitations, research on bone regeneration is being conducted actively. In this study, we investigate the effects of a three-dimensionally (3D) printed polycaprolactone (PCL)/tricalcium phosphate (TCP) scaffold on the osteogenic differentiation potential of adipose tissue-derived stem cells (ADSCs) and bone marrow-derived stem cells (BMSCs). METHODS We investigated the extent of osteogenic differentiation on the first and tenth day and fourth week after cell culture. Cytotoxicity of the 3D printed PCL/β-TCP scaffold was evaluated by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay, prior to osteogenic differentiation analysis. ADSCs and BMSCs were divided into three groups: C, only cultured cells; M, cells cultured in the 3D printed PCL/β-TCP scaffold; D, cells cultured in the 3D printed PCL/β-TCP scaffold with a bone differentiation medium. Alkaline phosphatase (ALP) activity assay, von Kossa staining, reverse transcription-polymerase chain reaction (RT-PCR), and Western blotting were performed for comparative analysis. RESULTS ALP assay and von Kossa staining revealed that group M had higher levels of osteogenic differentiation compared to group C. RT-PCR showed that gene expression was higher in group M than in group C, indicating that, compared to group C, osteogenic differentiation was more extensive in group M. Expression levels of proteins involved in ossification were higher in group M, as per the Western blotting results. CONCLUSION Osteogenic differentiation was increased in mesenchymal stromal cells (MSCs) cultured in the 3D printed PCL/TCP scaffold compared to the control group. Osteogenic differentiation activity of MSCs cultured in the 3D printed PCL/TCP scaffold was lower than that of cells cultured on the scaffold in bone differentiation medium. Collectively, these results indicate that the 3D printed PCL/TCP scaffold promoted osteogenic differentiation of MSCs and may be widely used for bone tissue engineering.
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Affiliation(s)
- Hannara Park
- Department of Plastic and Reconstructive Surgery, Daegu Fatima Hospital, Daegu, Korea
| | - Jin Soo Kim
- Department of Plastic and Reconstructive Surgery, Daegu Fatima Hospital, Daegu, Korea
| | - Eun Jung Oh
- Department of Plastic and Reconstructive Surgery, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Tae Jung Kim
- Department of Plastic and Reconstructive Surgery, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Hyun Mi Kim
- Department of Plastic and Reconstructive Surgery, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Jin Hyung Shim
- Department of Mechanical Engineering, Korea Polytechnic University, Siheung, Korea
| | - Won Soo Yoon
- Department of Mechanical Engineering, Korea Polytechnic University, Siheung, Korea
| | - Jung Bo Huh
- Department of Prosthodontics, Dental Research Institute, Institute of Translational Dental Science, School of Dentistry, Pusan National University, Yangsan, Korea
| | - Sung Hwan Moon
- Department of Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - Seong Soo Kang
- College of Veterinary Medicine, Chonnam National University, Gwangju, Korea
| | - Ho Yun Chung
- Department of Plastic and Reconstructive Surgery, School of Medicine, Kyungpook National University, Daegu, Korea
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Shi R, Huang Y, Ma C, Wu C, Tian W. Current advances for bone regeneration based on tissue engineering strategies. Front Med 2018; 13:160-188. [PMID: 30047029 DOI: 10.1007/s11684-018-0629-9] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2017] [Accepted: 12/14/2017] [Indexed: 01/07/2023]
Abstract
Bone tissue engineering (BTE) is a rapidly developing strategy for repairing critical-sized bone defects to address the unmet need for bone augmentation and skeletal repair. Effective therapies for bone regeneration primarily require the coordinated combination of innovative scaffolds, seed cells, and biological factors. However, current techniques in bone tissue engineering have not yet reached valid translation into clinical applications because of several limitations, such as weaker osteogenic differentiation, inadequate vascularization of scaffolds, and inefficient growth factor delivery. Therefore, further standardized protocols and innovative measures are required to overcome these shortcomings and facilitate the clinical application of these techniques to enhance bone regeneration. Given the deficiency of comprehensive studies in the development in BTE, our review systematically introduces the new types of biomimetic and bifunctional scaffolds. We describe the cell sources, biology of seed cells, growth factors, vascular development, and the interactions of relevant molecules. Furthermore, we discuss the challenges and perspectives that may propel the direction of future clinical delivery in bone regeneration.
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Affiliation(s)
- Rui Shi
- Institute of Traumatology and Orthopaedics, Beijing Laboratory of Biomedical Materials, Beijing Jishuitan Hospital, Beijing, 100035, China
| | - Yuelong Huang
- Department of Spine Surgery of Beijing Jishuitan Hospital, The Fourth Clinical Medical College of Peking University, Beijing, 100035, China
| | - Chi Ma
- Institute of Traumatology and Orthopaedics, Beijing Laboratory of Biomedical Materials, Beijing Jishuitan Hospital, Beijing, 100035, China
| | - Chengai Wu
- Institute of Traumatology and Orthopaedics, Beijing Laboratory of Biomedical Materials, Beijing Jishuitan Hospital, Beijing, 100035, China
| | - Wei Tian
- Institute of Traumatology and Orthopaedics, Beijing Laboratory of Biomedical Materials, Beijing Jishuitan Hospital, Beijing, 100035, China. .,Department of Spine Surgery of Beijing Jishuitan Hospital, The Fourth Clinical Medical College of Peking University, Beijing, 100035, China.
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Liu G, Wu R, Yang B, Deng C, Lu X, Walker SJ, Ma PX, Mou S, Atala A, Zhang Y. Human Urine-Derived Stem Cell Differentiation to Endothelial Cells with Barrier Function and Nitric Oxide Production. Stem Cells Transl Med 2018; 7:686-698. [PMID: 30011128 PMCID: PMC6127250 DOI: 10.1002/sctm.18-0040] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2018] [Revised: 04/10/2018] [Accepted: 04/20/2018] [Indexed: 12/19/2022] Open
Abstract
Endothelial cells (ECs) play a key role in revascularization within regenerating tissue. Stem cells are often used as an alternative cell source when ECs are not available. Several cell types have been used to give rise to ECs, such as umbilical cord vessels, or differentiated from somatic stem cells, embryonic, or induced pluripotent stem cells. However, the latter carry the potential risk of chronic immune rejection and oncogenesis. Autologous endothelial precursors are an ideal resource, but currently require an invasive procedure to obtain them from the patient's own blood vessels or bone marrow. Thus, the goal of this study was to determine whether urine-derived stem cells (USCs) could differentiate into functional ECs in vitro. Urine-derived cells were then differentiated into cells of the endothelial lineage using endothelial differentiation medium for 14 days. Changes in morphology and ultrastructure, and functional endothelial marker expression were assessed in the induced USCs in vitro. Grafts of the differentiated USCs were then subcutaneously injected into nude mice. Induced USCs expressed significantly higher levels of specific markers of ECs (CD31, vWF, eNOS) in vitro and in vivo, compared to nondifferentiated USCs. In addition, the differentiated USC formed intricate tubular networks and presented similar tight junctions, and migration and invasion ability, as well as ability to produce nitric oxide (NO) compared to controls. Using USCs as autologous EC sources for vessel, tissue engineering strategies can yield a sufficient number of cells via a noninvasive, simple, and low-cost method suitable for rapid clinical translation. Stem Cells Translational Medicine 2018 Stem Cells Translational Medicine 2018;7:686-698.
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Affiliation(s)
- Guihua Liu
- Reproductive Centre, Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guang Dong, People's Republic of China.,Wake Forest Institute of Regenerative Medicine
| | - Rongpei Wu
- Wake Forest Institute of Regenerative Medicine.,Department of Urology, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guang Dong, People's Republic of China
| | - Bin Yang
- Wake Forest Institute of Regenerative Medicine.,Department of Urology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China
| | - Chunhua Deng
- Department of Urology, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guang Dong, People's Republic of China
| | - Xiongbing Lu
- Department of Urology, The Second Affiliated Hospital of Nanchang University, Nanchang, People's Republic of China
| | | | - Peter X Ma
- School of Dentistry, Ann Arbor, Michigan, USA
| | - Steve Mou
- Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
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Pavathuparambil Abdul Manaph N, Al-Hawaas M, Bobrovskaya L, Coates PT, Zhou XF. Urine-derived cells for human cell therapy. Stem Cell Res Ther 2018; 9:189. [PMID: 29996911 PMCID: PMC6042455 DOI: 10.1186/s13287-018-0932-z] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Desirable cells for human cell therapy would be ones that can be generated by simple isolation and culture techniques using a donor sample obtained by non-invasive methods. To date, the different donor-specific cells that can be isolated from blood, skin, and hair require invasive methods for sample isolation and incorporate complex and costly reagents to culture. These cells also take considerable time for their in-vitro isolation and expansion. Previous studies suggest that donor-derived cells, namely urine stem cells and renal cells, may be isolated from human urine samples using a cost-effective and simple method of isolation, incorporating not such complex reagents. Moreover, the isolated cells, particularly urine stem cells, are superior to conventional stem cell sources in terms of favourable gene profile and inherent multipotent potential. Transdifferentiation or differentiation of human urine-derived cells can generate desirable cells for regenerative therapy. In this review, we intended to discuss the characteristics and therapeutic applications of urine-derived cells for human cell therapy. Conclusively, with detailed study and optimisation, urine-derived cells have a prospective future to generate functional lineage-specific cells for patients from a clinical translation point of view.
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Affiliation(s)
- Nimshitha Pavathuparambil Abdul Manaph
- Central Northern Adelaide Renal and Transplantation Service, Royal Adelaide Hospital, Adelaide, 5000 South Australia
- School of Pharmacy and Medical Sciences, Sansom Institute, University of South Australia, Adelaide, 5000 South Australia
- School of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, 5000 South Australia
| | - Mohammed Al-Hawaas
- School of Pharmacy and Medical Sciences, Sansom Institute, University of South Australia, Adelaide, 5000 South Australia
| | - Larisa Bobrovskaya
- School of Pharmacy and Medical Sciences, Sansom Institute, University of South Australia, Adelaide, 5000 South Australia
| | - Patrick T. Coates
- Central Northern Adelaide Renal and Transplantation Service, Royal Adelaide Hospital, Adelaide, 5000 South Australia
- School of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, 5000 South Australia
| | - Xin-Fu Zhou
- School of Pharmacy and Medical Sciences, Sansom Institute, University of South Australia, Adelaide, 5000 South Australia
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Human Urine-Derived Stem Cells: Potential for Cell-Based Therapy of Cartilage Defects. Stem Cells Int 2018; 2018:4686259. [PMID: 29765413 PMCID: PMC5932456 DOI: 10.1155/2018/4686259] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2017] [Revised: 02/25/2018] [Accepted: 03/19/2018] [Indexed: 02/05/2023] Open
Abstract
Stem cell therapy is considered an optimistic approach to replace current treatments for cartilage defects. Recently, human urine-derived stem cells (hUSCs), which are isolated from the urine, are studied as a promising candidate for many tissue engineering therapies due to their multipotency and sufficient proliferation activities. However, it has not yet been reported whether hUSCs can be employed in cartilage defects. In this study, we revealed that induced hUSCs expressed chondrogenic-related proteins, including aggrecan and collagen II, and their gene expression levels were upregulated in vitro. Moreover, we combined hUSCs with hyaluronic acid (HA) and injected hUSCs-HA into a rabbit knee joint with cartilage defect. Twelve weeks after the injection, the histologic analyses (HE, toluidine blue, and Masson trichrome staining), immunohistochemistry (aggrecan and collagen II), and histologic grade of the sample indicated that hUSCs-HA could stimulate much more neocartilage formation compared with hUSCs alone, pure HA, and saline, which only induced the modest cartilage regeneration. In this study, we demonstrated that hUSCs could be a potential cell source for stem cell therapies to treat cartilage-related defects in the future.
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Urine-Derived Stem Cells: The Present and the Future. Stem Cells Int 2017; 2017:4378947. [PMID: 29250119 PMCID: PMC5698822 DOI: 10.1155/2017/4378947] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2017] [Revised: 08/30/2017] [Accepted: 09/07/2017] [Indexed: 02/07/2023] Open
Abstract
Stem cell research provides promising strategies in improving healthcare for human beings. As a noninvasively obtained and easy-to-culture cell resource with relatively low expense, urine-derived stem cells have special advantages. They have been extensively studied on its proliferation ability and differentiation potential and were being reprogrammed to model diseases during the last decade. In this review, we intend to summarize the latest progress on the research of urine-derived stem cells for its broad application mainly in regenerative medicine and disease modeling, as well as in what is challenging currently. This minireview will highlight the potential application of urine-derived stem cells and provides possible direction of further research in the future.
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Zhang L, Guan Z, Ye JS, Yin YF, Stoltz JF, de Isla N. Research progress in liver tissue engineering. Biomed Mater Eng 2017; 28:S113-S119. [PMID: 28372286 DOI: 10.3233/bme-171632] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Liver transplantation is the definitive treatment for patients with end-stage liver diseases (ESLD). However, it is hampered by shortage of liver donor. Liver tissue engineering, aiming at fabricating new livers in vitro, provides a potential resolution for donor shortage. Three elements need to be considered in liver tissue engineering: seeding cell resources, scaffolds and bioreactors. Studies have shown potential cell sources as hepatocytes, hepatic cell line, mesenchymal stem cells and others. They need scaffolds with perfect biocompatiblity, suitable micro-structure and appropriate degradation rate, which are essential charateristics for cell attachment, proliferation and secretion in forming extracellular matrix. The most promising scaffolds in research include decellularized whole liver, collagens and biocompatible plastic. The development and function of cells in scaffold need a microenvironment which can provide them with oxygen, nutrition, growth factors, et al. Bioreactor is expected to fulfill these requirements by mimicking the living condition in vivo. Although there is great progress in these three domains, a large gap stays still between their researches and applications. Herein, we summarized the recent development in these three major fields which are indispensable in liver tissue engineering.
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Affiliation(s)
- Lei Zhang
- BRC, First Hospital of Kun Ming (Affiliated Calmette Hospital of Kunming Medical University), Kunming, China
| | - Zheng Guan
- BRC, First Hospital of Kun Ming (Affiliated Calmette Hospital of Kunming Medical University), Kunming, China
| | - Jun-Song Ye
- BRC, First Hospital of Kun Ming (Affiliated Calmette Hospital of Kunming Medical University), Kunming, China
| | - Yan-Feng Yin
- BRC, First Hospital of Kun Ming (Affiliated Calmette Hospital of Kunming Medical University), Kunming, China
| | - Jean-François Stoltz
- Lorraine University and CNRS UNR 7365, Medical college, Vandoeuvre-lès-Nancy, France.,CHRU Nancy, Unité Therapie Cellulaire et Tissulaire, Vandoeuvre-lès-Nancy, France
| | - Natalia de Isla
- Lorraine University and CNRS UNR 7365, Medical college, Vandoeuvre-lès-Nancy, France
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Murakami S, Miyaji H, Nishida E, Kawamoto K, Miyata S, Takita H, Akasaka T, Fugetsu B, Iwanaga T, Hongo H, Amizuka N, Sugaya T, Kawanami M. Dose effects of beta-tricalcium phosphate nanoparticles on biocompatibility and bone conductive ability of three-dimensional collagen scaffolds. Dent Mater J 2017; 36:573-583. [PMID: 28450672 DOI: 10.4012/dmj.2016-295] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Three-dimensional collagen scaffolds coated with beta-tricalcium phosphate (β-TCP) nanoparticles reportedly exhibit good bioactivity and biodegradability. Dose effects of β-TCP nanoparticles on biocompatibility and bone forming ability were then examined. Collagen scaffold was applied with 1, 5, 10, and 25 wt% β-TCP nanoparticle dispersion and designated TCP1, TCP5, TCP10, and TCP25, respectively. Compressive strength, calcium ion release and enzyme resistance of scaffolds with β-TCP nanoparticles applied increased with β-TCP dose. TCP5 showed excellent cell-ingrowth behavior in rat subcutaneous tissue. When TCP10 was applied, osteoblastic cell proliferation and rat cranial bone augmentation were greater than for any other scaffold. The bone area of TCP10 was 7.7-fold greater than that of non-treated scaffold. In contrast, TCP25 consistently exhibited adverse biological effects. These results suggest that the application dose of β-TCP nanoparticles affects the scaffold bioproperties; consequently, the bone conductive ability of TCP10 was remarkable.
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Affiliation(s)
- Shusuke Murakami
- Department of Periodontology and Endodontology, Hokkaido University Graduate School of Dental Medicine
| | - Hirofumi Miyaji
- Department of Periodontology and Endodontology, Hokkaido University Graduate School of Dental Medicine
| | - Erika Nishida
- Department of Periodontology and Endodontology, Hokkaido University Graduate School of Dental Medicine
| | - Kohei Kawamoto
- Department of Periodontology and Endodontology, Hokkaido University Graduate School of Dental Medicine
| | - Saori Miyata
- Department of Periodontology and Endodontology, Hokkaido University Graduate School of Dental Medicine
| | - Hiroko Takita
- Support Section for Education and Research, Hokkaido University Graduate School of Dental Medicine
| | - Tsukasa Akasaka
- Department of Dental Materials and Engineering, Hokkaido University Graduate School of Dental Medicine
| | - Bunshi Fugetsu
- Nano-Agri Lab, Policy Alternatives Research Institute, The University of Tokyo
| | - Toshihiko Iwanaga
- Laboratory of Histology and Cytology, Hokkaido University Graduate School of Medicine
| | - Hiromi Hongo
- Department of Developmental Biology of Hard Tissue, Hokkaido University Graduate School of Dental Medicine
| | - Norio Amizuka
- Department of Developmental Biology of Hard Tissue, Hokkaido University Graduate School of Dental Medicine
| | - Tsutomu Sugaya
- Department of Periodontology and Endodontology, Hokkaido University Graduate School of Dental Medicine
| | - Masamitsu Kawanami
- Department of Periodontology and Endodontology, Hokkaido University Graduate School of Dental Medicine
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Gao P, Han P, Jiang D, Yang S, Cui Q, Li Z. Effects of the donor age on proliferation, senescence and osteogenic capacity of human urine-derived stem cells. Cytotechnology 2017; 69:751-763. [PMID: 28409292 DOI: 10.1007/s10616-017-0084-5] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2016] [Accepted: 03/15/2017] [Indexed: 12/22/2022] Open
Abstract
To study the effects of the donor age on the application potential of human urine-derived stem cells (hUSCs) in bone tissue engineering, by comparing proliferation, senescence and osteogenic differentiation of hUSCs originated from volunteers with different ages. The urine samples were collected from 19 healthy volunteers (6 cases from children group aged from 5 to 14, 5 cases from middle-aged group aged from 30 to 40, and 8 cases from the elder group aged from 65 to 75), and hUSCs were isolated and cultured. The cell morphology was observed by microscope and the cell surface markers were identified by flow cytometry. Their abilities to undergo osteogenic, adipogenic and chondrogenic differentiation were determined in vitro, and cell proliferation analyses were performed using Cell Counting Kit-8 (CCK8) Assay. The senescence of hUSCs among three groups was assessed by senescence-associated β galactosidase staining. After osteogenic differentiation, the alkaline phosphatase (ALP) activity of hUSCs was measured and expression of osteogenic-related runt-related transcription factor 2 (RUNX2) and osteocalcin (OCN) was determined by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. The hUSCs isolated from urine samples were adherent cells displayed "rice gain"-like and "spindle-shaped" morphology, expressing surface markers of mesenchymal stem cells (MSCs) (CD73, CD90, CD105) and the peripheral cell marker (CD146), but not hematopoietic stem cell markers (CD34, CD45) or the embryonic stem cell marker (OCT3/4). The obtained hUSCs could be induced into osteogenic, adipogenic or chondrogenic differentiation. The hUSCs from the children group showed higher proliferation and lower tendency to senescence than those from the middle-aged and elder groups. After osteogenic induction, the ALP activity and RUNX2 and OCN expression of hUSCs from the children group were higher than those from the elder group. While no significant differences were observed when comparing the middle-aged group with the children group or the elder group. Donor age could influence the potency of hUSCs on proliferation, senescence and capacity of osteogenic differentiation. hUSCs from children group have shown higher proliferation, lower tendency to senescence, and stronger osteogenic capacity, which means to be more suitable for basic research and have better clinical application. Furthermore, hUSCs from all groups suggest the application potential in bone tissue engineering as seed cells.
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Affiliation(s)
- Peng Gao
- Department of Pediatric Surgery, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China
- Department of Pediatric Surgery, Harbin Children's Hospital, Harbin, China
| | - Peilin Han
- Department of Pediatric Surgery, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Dapeng Jiang
- Department of Pediatric Surgery, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China
- Department of Pediatric Urology, Shanghai Xinhua Hospital, Shanghai, China
| | - Shulong Yang
- Department of Pediatric Surgery, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Qingbo Cui
- Department of Pediatric Surgery, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Zhaozhu Li
- Department of Pediatric Surgery, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China.
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Hosseinpour S, Ghazizadeh Ahsaie M, Rezai Rad M, Baghani MT, Motamedian SR, Khojasteh A. Application of selected scaffolds for bone tissue engineering: a systematic review. Oral Maxillofac Surg 2017; 21:109-129. [PMID: 28194530 DOI: 10.1007/s10006-017-0608-3] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2016] [Accepted: 01/30/2017] [Indexed: 12/15/2022]
Abstract
PURPOSE The current systematic review investigated the results of application of some of the most commonly used scaffolds in conjugation with stem cells and growth factors in animal and clinical studies. METHODS A comprehensive electronic search was conducted according to the PRISMA guidelines in NCBI PMC and PubMed from January 1970 to December 2015 limited to English language publications with available full texts. In vivo studies in relation to "bone healing," "bone regeneration," and at least one of the following items were investigated: allograft, β-tricalcium phosphate, deproteinized bovine bone mineral, hydroxyapetite/tricalcium phosphate, nanohydroxyapatite, and composite scaffolds. RESULTS A total of 1252 articles were reviewed, and 46 articles completely fulfilled the inclusion criteria of this study. The highest bone regeneration has been achieved when combination of all three elements, given scaffolds, mesenchymal stem cells, and growth factors, were used. Among studies being reported in this review, bone marrow mesenchymal stem cells are the most studied mesenchymal stem cells, β-tricalcium phosphate is the most frequently used scaffold, and platelet-rich plasma is the most commonly used growth factor. CONCLUSION The current review aimed to inform reconstructive surgeons of how combinations of various mesenchymal stem cells, scaffolds, and growth factors enhance bone regeneration. The highest bone regeneration has been achieved when combination of all three elements, given scaffolds, mesenchymal stem cells, and growth factors, were used.
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Affiliation(s)
- Sepanta Hosseinpour
- School of Dentistry, Students' Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mitra Ghazizadeh Ahsaie
- School of Dentistry, Students' Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Maryam Rezai Rad
- Dental Research Center, Research Institute of Dental Research, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Taghi Baghani
- Department of Orthodontics, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Saeed Reza Motamedian
- Prosthodontics Department, Dental School, Shahed University of Medical Sciences, Tehran, Iran
| | - Arash Khojasteh
- Department of Tissue Engineering, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Elkhenany H, Bourdo S, Biris A, Anderson D, Dhar M. Important Considerations in the Therapeutic Application of Stem Cells in Bone Healing and Regeneration. STEM CELLS IN TOXICOLOGY AND MEDICINE 2016:458-480. [DOI: 10.1002/9781119135449.ch23] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Comparison of Osteogenesis between Adipose-Derived Mesenchymal Stem Cells and Their Sheets on Poly-ε-Caprolactone/β-Tricalcium Phosphate Composite Scaffolds in Canine Bone Defects. Stem Cells Int 2016; 2016:8414715. [PMID: 27610141 PMCID: PMC5004032 DOI: 10.1155/2016/8414715] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2016] [Revised: 07/01/2016] [Accepted: 07/05/2016] [Indexed: 01/08/2023] Open
Abstract
Multipotent mesenchymal stem cells (MSCs) and MSC sheets have effective potentials of bone regeneration. Composite polymer/ceramic scaffolds such as poly-ε-caprolactone (PCL)/β-tricalcium phosphate (β-TCP) are widely used to repair large bone defects. The present study investigated the in vitro osteogenic potential of canine adipose-derived MSCs (Ad-MSCs) and Ad-MSC sheets. Composite PCL/β-TCP scaffolds seeded with Ad-MSCs or wrapped with osteogenic Ad-MSC sheets (OCS) were also fabricated and their osteogenic potential was assessed following transplantation into critical-sized bone defects in dogs. The alkaline phosphatase (ALP) activity of osteogenic Ad-MSCs (O-MSCs) and OCS was significantly higher than that of undifferentiated Ad-MSCs (U-MSCs). The ALP, runt-related transcription factor 2, osteopontin, and bone morphogenetic protein 7 mRNA levels were upregulated in O-MSCs and OCS as compared to U-MSCs. In a segmental bone defect, the amount of newly formed bone was greater in PCL/β-TCP/OCS and PCL/β-TCP/O-MSCs/OCS than in the other groups. The OCS exhibit strong osteogenic capacity, and OCS combined with a PCL/β-TCP composite scaffold stimulated new bone formation in a critical-sized bone defect. These results suggest that the PCL/β-TCP/OCS composite has potential clinical applications in bone regeneration and can be used as an alternative treatment modality in bone tissue engineering.
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Tollemar V, Collier ZJ, Mohammed MK, Lee MJ, Ameer GA, Reid RR. Stem cells, growth factors and scaffolds in craniofacial regenerative medicine. Genes Dis 2016; 3:56-71. [PMID: 27239485 PMCID: PMC4880030 DOI: 10.1016/j.gendis.2015.09.004] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2015] [Accepted: 09/22/2015] [Indexed: 02/08/2023] Open
Abstract
Current reconstructive approaches to large craniofacial skeletal defects are often complicated and challenging. Critical-sized defects are unable to heal via natural regenerative processes and require surgical intervention, traditionally involving autologous bone (mainly in the form of nonvascularized grafts) or alloplasts. Autologous bone grafts remain the gold standard of care in spite of the associated risk of donor site morbidity. Tissue engineering approaches represent a promising alternative that would serve to facilitate bone regeneration even in large craniofacial skeletal defects. This strategy has been tested in a myriad of iterations by utilizing a variety of osteoconductive scaffold materials, osteoblastic stem cells, as well as osteoinductive growth factors and small molecules. One of the major challenges facing tissue engineers is creating a scaffold fulfilling the properties necessary for controlled bone regeneration. These properties include osteoconduction, osetoinduction, biocompatibility, biodegradability, vascularization, and progenitor cell retention. This review will provide an overview of how optimization of the aforementioned scaffold parameters facilitates bone regenerative capabilities as well as a discussion of common osteoconductive scaffold materials.
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Affiliation(s)
- Viktor Tollemar
- The University of Chicago Pritzker School of Medicine, Chicago, IL 60637, USA
- Department of Orthopedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA
- Laboratory of Craniofacial Biology and Development, Section of Plastic and Reconstructive Surgery, Department of Surgery, The University of Chicago Medicine, Chicago, IL 60637, USA
| | - Zach J. Collier
- The University of Chicago Pritzker School of Medicine, Chicago, IL 60637, USA
- Department of Orthopedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA
| | - Maryam K. Mohammed
- The University of Chicago Pritzker School of Medicine, Chicago, IL 60637, USA
- Department of Orthopedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA
| | - Michael J. Lee
- Department of Orthopedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA
| | - Guillermo A. Ameer
- Department of Surgery, Feinberg School of Medicine, Chicago, IL 60611, USA
- Biomedical Engineering Department, Northwestern University, Evanston, IL 60208, USA
| | - Russell R. Reid
- Laboratory of Craniofacial Biology and Development, Section of Plastic and Reconstructive Surgery, Department of Surgery, The University of Chicago Medicine, Chicago, IL 60637, USA
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Zhang J, Yang Y, Chen Y, Liu X, Guo S, Zhu L, Wang Y. An in situ phototriggered-imine-crosslink composite hydrogel for bone defect repair. J Mater Chem B 2016; 4:973-981. [PMID: 32263170 DOI: 10.1039/c5tb02377g] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
A novel in situ formed composite hydrogel based on the phototriggered imine crosslink mechanism with good biocompatibility and osteoinduction is developed for bone repair.
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Affiliation(s)
- Jieyuan Zhang
- Institute of Microsurgery on Extremities
- Shanghai Jiao Tong University
- Affiliated Sixth People's Hospital
- Shanghai 200233
- China
| | - Yunlong Yang
- Institute of Fine Chemicals
- East China University of Science and Technology
- Shanghai 200237
- China
| | - Yunfeng Chen
- Department of Orthopedic Surgery
- Shanghai Jiao Tong University Affiliated Sixth People's Hospital
- Shanghai 200233
- China
| | - Xiaolin Liu
- Institute of Microsurgery on Extremities
- Shanghai Jiao Tong University
- Affiliated Sixth People's Hospital
- Shanghai 200233
- China
| | - Shangchun Guo
- Institute of Microsurgery on Extremities
- Shanghai Jiao Tong University
- Affiliated Sixth People's Hospital
- Shanghai 200233
- China
| | - Linyong Zhu
- Institute of Fine Chemicals
- East China University of Science and Technology
- Shanghai 200237
- China
| | - Yang Wang
- Institute of Microsurgery on Extremities
- Shanghai Jiao Tong University
- Affiliated Sixth People's Hospital
- Shanghai 200233
- China
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