|
1
|
Liu Y, Zhou Z, Lu G, Zhang X, Shi D, Tong L, Chen D, Tuan RS, Li ZA. Musculoskeletal organoids: An emerging toolkit for establishing personalized models of musculoskeletal disorders and developing regenerative therapies. Acta Biomater 2025:S1742-7061(25)00362-9. [PMID: 40381929 DOI: 10.1016/j.actbio.2025.05.037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2025] [Revised: 05/09/2025] [Accepted: 05/14/2025] [Indexed: 05/20/2025]
Abstract
Musculoskeletal (MSK) conditions are the primary cause of physical disability globally. These disorders are physically and mentally debilitating and severely impact the patients' quality of life. As the median age of the world's population increases, there has been an intensifying urgency of developing efficacious therapies for various orthopaedic conditions. Furthermore, the highly heterogeneous nature of MSK conditions calls for a personalized approach to studying disease mechanisms and developing regenerative treatments. Organoids have emerged as an advanced approach to generating functional tissue/organ mimics in vitro, which hold promise in MSK regeneration, disease modeling, and therapeutic development. Herein, we review the preparation, characterization, and application of various MSK organoids. We highlight the potential of patient-specific organoids in the development of personalized medicine and discuss the challenges and opportunities in the future development of MSK organoids. STATEMENT OF SIGNIFICANCE: Despite decades of research, translation of MSK research into clinical applications remains limited, partially attributed to our inadequate understanding of disease mechanisms. To advance therapeutic development, there are critical needs for MSK disease models with higher clinical relevance and predictive power. Additionally, engineered constructs that closely mimic the structural and functional features of native MSK tissues are highly desirable. MSK organoids have emerged as a promising approach to meet the above requirements. To unleash the full potential of MSK organoids necessitates a comprehensive understanding of their categories, construction, development, functions, applications, and challenges. This review aims to fulfill this crucial need, aiming to accelerate the clinical translation of MSK organoid platforms to benefit millions of patients afflicted with MSK conditions.
Collapse
Affiliation(s)
- Yuwei Liu
- Department of Orthopedics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, PR China; Department of Biomedical Engineering, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; Department of Sports Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen 518035, Guangdong, PR China
| | - Zhilong Zhou
- Department of Biomedical Engineering, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China
| | - Gang Lu
- Institute for Tissue Engineering and Regenerative Medicine, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; Center for Neuromusculoskeletal Restorative Medicine, Hong Kong Science Park, Hong Kong Special Administrative Region of China
| | - Xin Zhang
- Institute of Sports Medicine, Beijing Key Laboratory of Sports Injuries, Peking University Third Hospital, Beijing, 100191 PR China
| | - Dongquan Shi
- Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, PR China
| | - Liping Tong
- Research Center for Computer-aided Drug Discovery, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, PR China
| | - Di Chen
- Research Center for Computer-aided Drug Discovery, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, PR China; Department of Pharmacology, Faculty of Pharmaceutical Sciences, Shenzhen University of Advanced Technology, Shenzhen 518000, PR China.
| | - Rocky S Tuan
- Department of Biomedical Engineering, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; Institute for Tissue Engineering and Regenerative Medicine, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; Center for Neuromusculoskeletal Restorative Medicine, Hong Kong Science Park, Hong Kong Special Administrative Region of China.
| | - Zhong Alan Li
- Department of Biomedical Engineering, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; Institute for Tissue Engineering and Regenerative Medicine, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; Center for Neuromusculoskeletal Restorative Medicine, Hong Kong Science Park, Hong Kong Special Administrative Region of China; Peter Hung Pain Research Institute, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region of China.
| |
Collapse
|
|
2
|
Jiang Q, Shao S, Li N, Zhang Z, Zhao L, Zhang H, Liu B. Live MSCs Characterizer Displays Stemness and Differentiation Using Colorful LV-cp Biosensors. ACS Sens 2025; 10:825-834. [PMID: 39907518 DOI: 10.1021/acssensors.4c02356] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2025]
Abstract
Mesenchymal stem cells (MSCs) have garnered significant attention in biomedical research due to their accessibility and remarkable differentiation potential. However, the lack of efficient and convenient living cell monitoring methods limits their widespread application in tissue engineering and stem cell therapy. Therefore, we present progress in the development of a novel series of fluorescent protein (FP) sensors based on turn-on fluorescent protein biosensors (Turn-on FPBs), termed the LV-cp biosensor system (novel live cell permuted fluorescent protein biosensors). Utilizing phage display technology to screen for affinity peptides specifically targeting MSCs and chondrocytes, the LV-cp were engineered by subcloning these peptides into permuted fluorescent proteins, thereby integrating the fluorescence activation mechanism with the affinity peptides and achieving highly accurate detection and identification of these two cell types using living cells as "fluorescence keys." This system provides a simplified, nontoxic method to replace traditional antibody kits, and strong fluorescence signals can be obtained through various fluorescence detection devices. In addition, the LV-cp biosensors enabled dynamic observation of MSCs differentiation into chondrocytes through changes in the cell fluorescence colors.
Collapse
Affiliation(s)
- Qingyun Jiang
- Cancer Hospital of Dalian University of Technology, Shenyang 110042, P. R. China
- Faculty of Medicine, Liaoning Key Lab of Integrated Circuit and Biomedical Electronic System, Dalian University of Technology, Dalian 116024, P. R. China
| | - Shuai Shao
- Cancer Hospital of Dalian University of Technology, Shenyang 110042, P. R. China
- Faculty of Medicine, Liaoning Key Lab of Integrated Circuit and Biomedical Electronic System, Dalian University of Technology, Dalian 116024, P. R. China
| | - Na Li
- Cancer Hospital of Dalian University of Technology, Shenyang 110042, P. R. China
- Faculty of Medicine, Liaoning Key Lab of Integrated Circuit and Biomedical Electronic System, Dalian University of Technology, Dalian 116024, P. R. China
| | - Zhengyao Zhang
- School of Chemical Engineering, Ocean and Life Sciences, Dalian University of Technology, Panjin 124221, P. R. China
| | - Luming Zhao
- Cancer Hospital of Dalian University of Technology, Shenyang 110042, P. R. China
- Faculty of Medicine, Liaoning Key Lab of Integrated Circuit and Biomedical Electronic System, Dalian University of Technology, Dalian 116024, P. R. China
| | - Hangyu Zhang
- Cancer Hospital of Dalian University of Technology, Shenyang 110042, P. R. China
- Faculty of Medicine, Liaoning Key Lab of Integrated Circuit and Biomedical Electronic System, Dalian University of Technology, Dalian 116024, P. R. China
| | - Bo Liu
- Cancer Hospital of Dalian University of Technology, Shenyang 110042, P. R. China
- Faculty of Medicine, Liaoning Key Lab of Integrated Circuit and Biomedical Electronic System, Dalian University of Technology, Dalian 116024, P. R. China
| |
Collapse
|
|
3
|
Zhang Y, Shi L, Li X, Liu Y, Zhang G, Wang Y. Placental stem cells-derived exosomes stimulate cutaneous wound regeneration via engrailed-1 inhibition. Front Bioeng Biotechnol 2022; 10:1044773. [PMID: 36568306 PMCID: PMC9780460 DOI: 10.3389/fbioe.2022.1044773] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Accepted: 11/28/2022] [Indexed: 12/13/2022] Open
Abstract
Introduction: Skin wounds generally heal by scarring, a fibrotic process mediated by the Engrailed-1 (EN1) fibroblast lineage. Scar is detrimental to tissue structure and function, but perfect healing in clinical settings remains to be explored. Recent studies have shown that mesenchymal stem cell (MSC) transplantation can reduce scarring Methods: Here, we investigated the effects of placental MSCs (pMSCs) and exosomes derived from pMSCs (pMSC-exos) on wound healing using a full-thickness rat model. Results: The results showed that placental MSCs significantly accelerated the wound healing rate. Moreover, placental MSCs improved the quality of wound healing, including regenerating cutaneous appendages (hair follicles and sebaceous glands), decreasing collagen I and increasing collagen III, and improving collagen pattern (basket-wave-like) in the healed skin. placental MSCs treatment also increased the regeneration of blood vessels. Importantly, all these listed effects of placental MSCs were comparable to those of exosomes derived from pMSCs, but significantly stronger than those of adipose MSC-derived exosomes (aMSC-exos). Further studies showed that the effects of placental MSCs and exosomes derived from pMSCs on wound regeneration may be mainly achieved via the down-regulation of the Yes-associated protein signaling pathway, thus inhibiting the activation of EN1. Discussion: In summary, placental MSCs could effectively stimulate wound regeneration, and their effect could be achieved through their exosomes. This suggests that exosomes derived from pMSCs treatment could be used as a novel cell-free approach to induce wound regeneration in clinical settings.
Collapse
Affiliation(s)
- Yan Zhang
- China-Japan Union Hospital of Jilin University, Changchun, China
| | - Liyan Shi
- China-Japan Union Hospital of Jilin University, Changchun, China
| | - Xiuying Li
- China-Japan Union Hospital of Jilin University, Changchun, China
| | - Yang Liu
- Jilin Province People’s Hospital, Changchun, China
| | - Guokun Zhang
- Institute of Antler Science and Product Technology, Changchun Sci-Tech University, Changchun, China
| | - Yimin Wang
- China-Japan Union Hospital of Jilin University, Changchun, China
| |
Collapse
|
|
4
|
Migliorini F, Berton A, Salvatore G, Candela V, Khan W, Longo UG, Denaro V. Autologous Chondrocyte Implantation and Mesenchymal Stem Cells for the Treatments of Chondral Defects of the Knee- A Systematic Review. Curr Stem Cell Res Ther 2021; 15:547-556. [PMID: 32081109 DOI: 10.2174/1574888x15666200221122834] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2019] [Revised: 10/23/2019] [Accepted: 01/09/2020] [Indexed: 01/05/2023]
Abstract
BACKGROUND There is still a lack of consensus about the best treatment of chondral defects of the knee. We conducted a systematic PRISMA review to evaluate clinical outcomes of Autologous Chondrocyte Implantation (ACI) and Mesenchymal Stem Cell (MSC) injections for the treatment of focal chondral defects of the knee. METHODS A systematic review of literature was performed according to the PRISMA guidelines. All the articles reporting data on ACI and MSC treatments for chondral defects of the knee were considered for inclusion. The main databases were accessed: PubMed, Medline, CINAHL, Cochrane, Embase and Google Scholar. The statistical analysis was performed using the Review Manager Software. RESULTS In the p-ACI group (987 knees), the Cincinnati Score improved by 18.94% (p=0.1), VAS by 38% (p=0.01), Tegner score by 19.11% (p=0.03), Lysholm score by 22.40% (p=0.01), IKCD by 27.36% (p=0.003). In the c-ACI group (444 knees), the Cincinnati Score improved by 23.80% (p=0.08), KOOS by 23.48% (p=0.03), VAS by 33.2% (p=0.005), IKDC by 33.30% (p=0.005). In the m-ACI group (599 knees), the Cincinnati Score improved by 26.80% (p=0.08), KOOS by 31.59% (p=0.1), VAS by 30.43% (p=0.4), Tegner score by 23.1% (p=0.002), Lysholm score by 31.14% (p=0.004), IKCD by 30.57% (p<0.001). In the MSCs group (291 knees), the KOOS improved by 29.7% (p=0.003), VAS by 41.89% (p<0.001), Tegner score by 25.81% (p=0.003), Lysholm score by 36.96% (p<0.001), IKCD by 30.57% (p=0.001). CONCLUSION Both ACI and MSC therapies can be considered as a concrete solution to treat focal chondral defects of the knee.
Collapse
Affiliation(s)
- Filippo Migliorini
- Department of Orthopaedic and Trauma Surgery, Campus Bio-Medico University, Via Alvaro del Portillo, 200, 00128 Trigoria, Rome, Italy
| | - Alessandra Berton
- Department of Orthopaedic and Trauma Surgery, Campus Bio-Medico University, Via Alvaro del Portillo, 200, 00128 Trigoria, Rome, Italy
| | - Giuseppe Salvatore
- Department of Orthopaedic and Trauma Surgery, Campus Bio-Medico University, Via Alvaro del Portillo, 200, 00128 Trigoria, Rome, Italy
| | - Vincenzo Candela
- Department of Orthopaedic and Trauma Surgery, Campus Bio-Medico University, Via Alvaro del Portillo, 200, 00128 Trigoria, Rome, Italy
| | - Wasim Khan
- Division of Trauma & Orthopaedic Surgery, University of Cambridge, Addenbrooke's Hospital, Cambridge, CB2 2QQ, United Kingdom
| | - Umile G Longo
- Department of Orthopaedic and Trauma Surgery, Campus Bio-Medico University, Via Alvaro del Portillo, 200, 00128 Trigoria, Rome, Italy
| | - Vincenzo Denaro
- Department of Orthopaedic and Trauma Surgery, Campus Bio-Medico University, Via Alvaro del Portillo, 200, 00128 Trigoria, Rome, Italy
| |
Collapse
|
|
5
|
Checchi M, Bertacchini J, Cavani F, Magarò MS, Reggiani Bonetti L, Pugliese GR, Tamma R, Ribatti D, Maurel DB, Palumbo C. Scleral ossicles: angiogenic scaffolds, a novel biomaterial for regenerative medicine applications. Biomater Sci 2019; 8:413-425. [PMID: 31738355 DOI: 10.1039/c9bm01234f] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Given the current prolonged life expectancy, various pathologies affect increasingly the aging subjects. Regarding the musculoskeletal apparatus, bone fragility induces more susceptibility to fractures, often not accompanied by good ability of self-repairing, in particular when critical-size defects (CSD) occur. Currently orthopedic surgery makes use of allografting and autografting which, however, have limitations due to the scarce amount of tissue that can be taken from the donor, the possibility of disease transmission and donor site morbidity. The need to develop new solutions has pushed the field of tissue engineering (TE) research to study new scaffolds to be functionalized in order to obtain constructs capable of promoting tissue regeneration and achieve stable bone recovery over time. This investigation focuses on the most important aspect related to bone tissue regeneration: the angiogenic properties of the scaffold to be used. As an innovative solution, scleral ossicles (SOs), previously characterized as natural, biocompatible and spontaneously decellularized scaffolds used for bone repair, were tested for angiogenic potential and biocompatibility. To reach this purpose, in ovo Chorioallantoic Membrane Assay (CAM) was firstly used to test the angiogenic potential; secondly, in vivo subcutaneous implantation of SOs (in a rat model) was performed in order to assess the biocompatibility and the inflammatory response. Finally, thanks to the analysis of mass spectrometry (LCMSQE), the putative proteins responsible for the SO angiogenic properties were identified. Thus, a novel natural biomaterial is proposed, which is (i) able to induce an angiogenic response in vivo by subcutaneous implantation in a non-immunodeficient animal model, (ii) which does not induce any inflammatory response, and (iii) is useful for regenerative medicine application for the healing of bone CSD.
Collapse
Affiliation(s)
- Marta Checchi
- Department of Biomedical, Metabolic Science and Neuroscience, University of Modena and Reggio Emilia, 41125 Modena, Italy.
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
6
|
Ma R, Schär M, Chen T, Wang H, Wada S, Ju X, Deng XH, Rodeo SA. Use of Human Placenta-Derived Cells in a Preclinical Model of Tendon Injury. J Bone Joint Surg Am 2019; 101:e61. [PMID: 31274724 DOI: 10.2106/jbjs.15.01381] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
BACKGROUND Emerging data suggest that human cells derived from extraembryonic tissues may have favorable musculoskeletal repair properties. The purpose of this study was to determine whether the injection of human placenta-derived mesenchymal-like stromal cells, termed placental expanded cells (PLX-PAD), would improve tendon healing in a preclinical model of tendinopathy. METHODS Sixty male Sprague-Dawley rats underwent bilateral patellar tendon injection with either saline solution (control) or PLX-PAD cells (2 × 10 cells/100 µL) 6 days after collagenase injection to induce tendon degeneration. Animals were killed at specific time points for biomechanical, histological, and gene expression analyses of the healing patellar tendons. RESULTS Biomechanical testing 2 weeks after the collagenase injury demonstrated better biomechanical properties in the tendons treated with PLX-PAD cells. The load to failure of the PLX-PAD-treated tendons was higher than that of the saline-solution-treated controls at 2 weeks (77.01 ± 10.51 versus 58.87 ± 11.97 N, p = 0.01). There was no significant difference between the 2 groups at 4 weeks. There were no differences in stiffness at either time point. Semiquantitative histological analysis demonstrated no significant differences in collagen organization or cellularity between the PLX-PAD and saline-solution-treated tendons. Gene expression analysis demonstrated higher levels of interleukin-1β (IL-1β) and IL-6 early in the healing process in the PLX-PAD-treated tendons. CONCLUSIONS Human placenta-derived cell therapy induced an early inflammatory response and a transient beneficial effect on tendon failure load in a model of collagenase-induced tendon degeneration. CLINICAL RELEVANCE Human extraembryonic tissues, such as the placenta, are an emerging source of cells for musculoskeletal repair and may hold promise as a point-of-care cell therapy for tendon injuries.
Collapse
Affiliation(s)
- Richard Ma
- Missouri Orthopaedic Institute, University of Missouri, Columbia, Missouri
| | - Michael Schär
- Sports Medicine and Shoulder Service, The Hospital for Special Surgery, New York, NY
| | - Tina Chen
- Missouri Orthopaedic Institute, University of Missouri, Columbia, Missouri
| | - Hongsheng Wang
- Sports Medicine and Shoulder Service, The Hospital for Special Surgery, New York, NY
| | - Susumu Wada
- Sports Medicine and Shoulder Service, The Hospital for Special Surgery, New York, NY
| | - Xiadong Ju
- Sports Medicine and Shoulder Service, The Hospital for Special Surgery, New York, NY
| | - Xiang-Hua Deng
- Sports Medicine and Shoulder Service, The Hospital for Special Surgery, New York, NY
| | - Scott A Rodeo
- Sports Medicine and Shoulder Service, The Hospital for Special Surgery, New York, NY
| |
Collapse
|
|
7
|
Naseer N, Bashir S, Latief N, Latif F, Khan SN, Riazuddin S. Human amniotic membrane as differentiating matrix for in vitro chondrogenesis. Regen Med 2018; 13:821-832. [PMID: 30299207 DOI: 10.2217/rme-2018-0017] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Aim: The aim of the present study is to use human amniotic membrane (HAM) for in vitro chondrogenesis of placenta-derived mesenchymal stem cells (MSCs) and umbilical cord-derived MSCs. Materials & methods: MSCs from the placenta and umbilical cord were isolated, characterized by immunophenotyping and after analyzing their rate of proliferation, cytotoxicity and viability, chondrogenesis was performed on plastic adherent surface and on HAM. Results: Successfully isolated and characterized placenta-derived MSCs and umbilical cord-derived MSCs revealed positive expression of MSCs markers CD90, CD73, CD105 and CD49d, while they were negative for CD45. Both types of cells in the presence of chondrogenic induction medium on plastic adherent surface and HAM showed aggregates of proteoglycan and strong expression of COL2A1 (collagen 2) and ACAN1 (aggrecan). Conclusion: HAM supported proliferation as well as chondrogenesis of MSCs and provide novelty of HAM utilization as an efficient natural delivery matrix for stem cell transplantation.
Collapse
Affiliation(s)
- Nadia Naseer
- Centre of Excellence in Molecular Biology, 87 West Canal Bank Road, Thokar Niazbaig Lahore, Punjab, 53700 Pakistan
| | - Saliha Bashir
- Centre of Excellence in Molecular Biology, 87 West Canal Bank Road, Thokar Niazbaig Lahore, Punjab, 53700 Pakistan
| | - Noreen Latief
- Centre of Excellence in Molecular Biology, 87 West Canal Bank Road, Thokar Niazbaig Lahore, Punjab, 53700 Pakistan
| | - Farzana Latif
- Ameer-ud-din Medical College, Post Graduate Medical Institute (PGMI), Lahore General Hospital, 6-Abdur Rehman Chughtai Road (Birdwood Road), Jail Road, Shadman, Lahore,54000 Pakistan
| | - Shaheen N Khan
- Centre of Excellence in Molecular Biology, 87 West Canal Bank Road, Thokar Niazbaig Lahore, Punjab, 53700 Pakistan
| | - Sheikh Riazuddin
- Centre of Excellence in Molecular Biology, 87 West Canal Bank Road, Thokar Niazbaig Lahore, Punjab, 53700 Pakistan
- Allama Iqbal Medical College, University of Health Sciences, Lahore, Jinnah hospital Moulana Shabir Ahmed Usmani Road, Faisal Town Lahore 54550 Pakistan
- Shaheed Zulfiqar Ali Bhutto Medical University (SZABMU), PIMS, G-8/3, Islamabad, 44000 Pakistan
| |
Collapse
|
|
8
|
Smolar J, Horst M, Sulser T, Eberli D. Bladder regeneration through stem cell therapy. Expert Opin Biol Ther 2018; 18:525-544. [DOI: 10.1080/14712598.2018.1439013] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Jakub Smolar
- Department of Urology, University Hospital Zurich, Schlieren, Switzerland
| | - Maya Horst
- Department of Urology, University Children’s Hospital Zurich, Zurich, Switzerland
| | - Tulio Sulser
- Department of Urology, University Hospital Zurich, Zurich, Switzerland
| | - Daniel Eberli
- Department of Urology, University Hospital Zurich, Zurich, Switzerland
| |
Collapse
|
|
9
|
Bakhshandeh B, Zarrintaj P, Oftadeh MO, Keramati F, Fouladiha H, Sohrabi-Jahromi S, Ziraksaz Z. Tissue engineering; strategies, tissues, and biomaterials. Biotechnol Genet Eng Rev 2018; 33:144-172. [PMID: 29385962 DOI: 10.1080/02648725.2018.1430464] [Citation(s) in RCA: 112] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Current tissue regenerative strategies rely mainly on tissue repair by transplantation of the synthetic/natural implants. However, limitations of the existing strategies have increased the demand for tissue engineering approaches. Appropriate cell source, effective cell modification, and proper supportive matrices are three bases of tissue engineering. Selection of appropriate methods for cell stimulation, scaffold synthesis, and tissue transplantation play a definitive role in successful tissue engineering. Although the variety of the players are available, but proper combination and functional synergism determine the practical efficacy. Hence, in this review, a comprehensive view of tissue engineering and its different aspects are investigated.
Collapse
Affiliation(s)
- Behnaz Bakhshandeh
- a Department of Biotechnology, College of Science , University of Tehran , Tehran , Iran
| | - Payam Zarrintaj
- b School of Chemical Engineering, College of Engineering , University of Tehran , Tehran , Iran
| | - Mohammad Omid Oftadeh
- a Department of Biotechnology, College of Science , University of Tehran , Tehran , Iran.,c Stem Cell Technology Research Center , Tehran , Iran
| | - Farid Keramati
- a Department of Biotechnology, College of Science , University of Tehran , Tehran , Iran
| | - Hamideh Fouladiha
- a Department of Biotechnology, College of Science , University of Tehran , Tehran , Iran
| | - Salma Sohrabi-Jahromi
- d Gottingen Center for Molecular Biosciences , Georg August University , Göttingen , Germany
| | | |
Collapse
|
|
10
|
Barba M, Di Taranto G, Lattanzi W. Adipose-derived stem cell therapies for bone regeneration. Expert Opin Biol Ther 2017; 17:677-689. [PMID: 28374644 DOI: 10.1080/14712598.2017.1315403] [Citation(s) in RCA: 49] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Cell-based therapies exploit the heterogeneous and self-sufficient biological environment of stem cells to restore, maintain and improve tissue functions. Adipose-derived stem cells (ASCs) are, to this aim, promising cell types thanks to advantageous isolation procedures, growth kinetics, plasticity and trophic properties. Specifically, bone regeneration represents a suitable, though often challenging, target setting to test and apply ASC-based therapeutic strategies. Areas covered: ASCs are extremely plastic and secrete bioactive peptides that mediate paracrine functions, mediating their trophic actions in vivo. Numerous preclinical studies demonstrated that ASCs improve bone healing. Clinical trials are ongoing to validate the clinical feasibility of these approaches. This review is intended to define the state-of-the-art on ASCs, encompassing the biological features that make them suitable for bone regenerative strategies, and to provide an update on existing preclinical and clinical applications. Expert opinion: ASCs offer numerous advantages over other stem cells in terms of feasibility of clinical translation. Data obtained from in vivo experimentation are encouraging, and clinical trials are ongoing. More robust validations are thus expected to be achieved during the next few years, and will likely pave the way to optimized patient-tailored treatments for bone regeneration.
Collapse
Affiliation(s)
- Marta Barba
- a Institute of Anatomy and Cell Biology , Università Cattolica del Sacro Cuore , Rome , Italy
| | - Giuseppe Di Taranto
- b Department of Plastic, Reconstructive and Aesthetic Surgery , University of Rome "Sapienza" , Policlinico Umberto I, Rome , Italy
| | - Wanda Lattanzi
- a Institute of Anatomy and Cell Biology , Università Cattolica del Sacro Cuore , Rome , Italy
| |
Collapse
|
|
11
|
Bonaventura G, Chamayou S, Liprino A, Guglielmino A, Fichera M, Caruso M, Barcellona ML. Different Tissue-Derived Stem Cells: A Comparison of Neural Differentiation Capability. PLoS One 2015; 10:e0140790. [PMID: 26517263 PMCID: PMC4627815 DOI: 10.1371/journal.pone.0140790] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2014] [Accepted: 09/30/2015] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND Stem cells are capable of self-renewal and differentiation into a wide range of cell types with multiple clinical and therapeutic applications. Stem cells are providing hope for many diseases that currently lack effective therapeutic methods, including strokes, Huntington's disease, Alzheimer's and Parkinson's disease. However, the paucity of suitable cell types for cell replacement therapy in patients suffering from neurological disorders has hampered the development of this promising therapeutic approach. AIM The innovative aspect of this study has been to evaluate the neural differentiation capability of different tissue-derived stem cells coming from different tissue sources such as bone marrow, umbilical cord blood, human endometrium and amniotic fluid, cultured under the same supplemented media neuro-transcription factor conditions, testing the expression of neural markers such as GFAP, Nestin and Neurofilaments using the immunofluorescence staining assay and some typical clusters of differentiation such as CD34, CD90, CD105 and CD133 by using the cytofluorimetric test assay. RESULTS Amniotic fluid derived stem cells showed a more primitive phenotype compared to the differentiating potential demonstrated by the other stem cell sources, representing a realistic possibility in the field of regenerative cell therapy suitable for neurodegenerative diseases.
Collapse
Affiliation(s)
- Gabriele Bonaventura
- Department of Pharmaceutical Science, Biochemistry Section, University of Catania, Catania, Italy
- Institute of Neurological Sciences, Italian National Research Council, Catania, Italy
| | - Sandrine Chamayou
- Unità di Medicina della Riproduzione, Fondazione Hera, Sant’Agata Li Battiati (CT), Italy
| | - Annalisa Liprino
- Department of Obstetrics and Gynecology and Radiological Sciences (OGiRA), University of Catania, Catania, Italy
| | - Antonino Guglielmino
- Unità di Medicina della Riproduzione, Fondazione Hera, Sant’Agata Li Battiati (CT), Italy
| | - Michele Fichera
- Department of Obstetrics and Gynecology and Radiological Sciences (OGiRA), University of Catania, Catania, Italy
| | - Massimo Caruso
- Department of Clinic and Molecular Biomedicine, University of Catania, Catania, Italy
| | - Maria Luisa Barcellona
- Department of Pharmaceutical Science, Biochemistry Section, University of Catania, Catania, Italy
| |
Collapse
|
|
12
|
Silva KR, Liechocki S, Carneiro JR, Claudio-da-Silva C, Maya-Monteiro CM, Borojevic R, Baptista LS. Stromal-vascular fraction content and adipose stem cell behavior are altered in morbid obese and post bariatric surgery ex-obese women. Stem Cell Res Ther 2015; 6:72. [PMID: 25884374 PMCID: PMC4435525 DOI: 10.1186/s13287-015-0029-x] [Citation(s) in RCA: 52] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2014] [Revised: 01/29/2015] [Accepted: 03/02/2015] [Indexed: 12/11/2022] Open
Abstract
INTRODUCTION Subcutaneous adipose tissue is an interesting source of autologous stem cells with a fundamental role in the pathophysiology of obesity, metabolic syndromes and insulin resistance. We hypothesize that obesity could alter the stromal-vascular fraction (SVF) and adipose stem cell (ASCs) functions, which could compromise its regenerative behavior. Furthermore, we aimed to evaluate whether ASCs derived from post bariatric surgery ex-obese women maintain their functions in a similar fashion as do those from individuals who have never been obese. METHODS The SVF of subcutaneous adipose tissue from control (n = 6, body mass index - BMI - 27.5 ± 0.5 kg/m(2)), obese (n = 12, BMI 46.2 ± 5.1 kg/m(2)) and post bariatric surgery ex-obese (n = 7, initial BMI 47.8 ± 1.3 kg/m(2); final BMI 28.1 ± 1.1 kg/m(2)) women were isolated and evaluated by flow cytometry. ASCs were tested for lipid accumulation by perilipin, adipose differentiation-related protein (ADRP) and Oil Red O staining after adipogenic stimulus. The cytokines secreted by the ASCs and after lipid accumulation induction were also evaluated. RESULTS The subcutaneous adipose tissue of obese and post bariatric surgery ex-obese women was enriched in pericytes (p = 0.0345). The number of supra-adventitial cells was not altered in the obese patients, but it was highly enriched in the post bariatric surgery ex-obese women (p = 0.0099). The ASCs of the post bariatric surgery ex-obese patients secreted more MCP-1 (monocyte chemoattractant protein-1; p = 0.0078). After lipid accumulation induction, the ASCs of the patients in all groups secreted less IL-6 than the ASCs with no adipogenic stimulus (p < 0.0001). Obese ASCs with lipid accumulation secreted the highest amount of IL-6 (p < 0.001) whereas the ASCs from the controls secreted the highest amount of adiponectin (p < 0.0001). The ASCs from the post bariatric surgery ex-obese patients showed the highest levels of lipid accumulation whereas those from the obese women had the lowest levels (p < 0.0001). CONCLUSIONS SVF content and ASC behavior are altered in the subcutaneous adipose tissue of morbid obese women; these changes are not completely restored after bariatric surgery-induced weight loss. The cellular alterations described in this study could affect the regenerative effects of adipose stem cells. Further investigations are required to avoid jeopardizing the development of autologous stem cell-based therapies.
Collapse
Affiliation(s)
- Karina R Silva
- Programa de Pós-graduação em Clínica Médica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-913, Brazil. .,Núcleo Multidisciplinar de Pesquisa UFRJ - Xerém em Biologia (Numpex-Bio), Universidade Federal do Rio de Janeiro, Polo Xerém, Duque de Caxias, RJ 25245-390, Brazil. .,Programa de Bioengenharia, Diretoria de Programas, Instituto Nacional de Metrologia, Qualidade e Tecnologia (Inmetro), Duque de Caxias, RJ 25250-020, Brazil.
| | - Sally Liechocki
- Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ 21.040-900, Brazil.
| | - João R Carneiro
- Departamento de Nutrologia do Hospital Universitário Clementino Fraga Filho, Universidade Fereal do Rio de Janeiro, Rio de Janeiro, RJ 21941-913, Brazil.
| | - Cesar Claudio-da-Silva
- Serviço de Cirurgia Plástica, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-913, Brazil.
| | - Clarissa M Maya-Monteiro
- Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ 21.040-900, Brazil.
| | - Radovan Borojevic
- Programa de Pós-graduação em Clínica Médica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-913, Brazil. .,Programa de Bioengenharia, Diretoria de Programas, Instituto Nacional de Metrologia, Qualidade e Tecnologia (Inmetro), Duque de Caxias, RJ 25250-020, Brazil.
| | - Leandra S Baptista
- Programa de Pós-graduação em Clínica Médica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-913, Brazil. .,Núcleo Multidisciplinar de Pesquisa UFRJ - Xerém em Biologia (Numpex-Bio), Universidade Federal do Rio de Janeiro, Polo Xerém, Duque de Caxias, RJ 25245-390, Brazil. .,Programa de Bioengenharia, Diretoria de Programas, Instituto Nacional de Metrologia, Qualidade e Tecnologia (Inmetro), Duque de Caxias, RJ 25250-020, Brazil.
| |
Collapse
|
|
13
|
Baptista LS, Silva KR, Borojevic R. Obesity and weight loss could alter the properties of adipose stem cells? World J Stem Cells 2015; 7:165-173. [PMID: 25621116 PMCID: PMC4300927 DOI: 10.4252/wjsc.v7.i1.165] [Citation(s) in RCA: 44] [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: 07/26/2014] [Revised: 09/22/2014] [Accepted: 10/27/2014] [Indexed: 02/06/2023] Open
Abstract
The discovery that adipose tissue represents an interesting source of multipotent stem cells has led to many studies exploring the clinical potential of these cells in cell-based therapies. Recent advances in understanding the secretory capacity of adipose tissue and the role of adipokines in the development of obesity and associated disorders have added a new dimension to the study of adipose tissue biology in normal and diseased states. Subcutaneous adipose tissue forms the interface between the clinical application of regenerative medicine and the establishment of the pathological condition of obesity. These two facets of adipose tissue should be understood as potentially related phenomena. Because of the functional characteristics of adipose stem cells, these cells represent a fundamental tool for understanding how these two facets are interconnected and could be important for therapeutic applications. In fact, adipose tissue stem cells have multiple functions in obesity related to adipogenic, angiogenic and secretory capacities. In addition, we have also previously described a predominance of larger blood vessels and an adipogenic memory in the subcutaneous adipose tissue after massive weight loss subsequent to bariatric surgery (ex-obese patients). Understanding the reversibility of the behavior of adipose stem cells in obeses and in weight loss is relevant to both physiological studies and the potential use of these cells in regenerative medicine.
Collapse
|
|
14
|
Lankford L, Selby T, Becker J, Ryzhuk V, Long C, Farmer D, Wang A. Early gestation chorionic villi-derived stromal cells for fetal tissue engineering. World J Stem Cells 2015; 7:195-207. [PMID: 25621120 PMCID: PMC4300931 DOI: 10.4252/wjsc.v7.i1.195] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2014] [Revised: 11/04/2014] [Accepted: 11/07/2014] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the potential for early gestation placenta-derived mesenchymal stromal cells (PMSCs) for fetal tissue engineering. METHODS PMSCs were isolated from early gestation chorionic villus tissue by explant culture. Chorionic villus sampling (CVS)-size tissue samples (mean = 35.93 mg) were used to test the feasibility of obtaining large cell numbers from CVS within a clinically relevant timeframe. We characterized PMSCs isolated from 6 donor placentas by flow cytometry immunophenotyping, multipotency assays, and through immunofluorescent staining. Protein secretion from PMSCs was examined using two cytokine array assays capable of probing for over 70 factors in total. Delivery vehicle compatibility of PMSCs was determined using three common scaffold systems: fibrin glue, collagen hydrogel, and biodegradable nanofibrous scaffolds made from a combination of polylactic acid (PLA) and poly(lactic-co-glycolic acid) (PLGA). Viral transduction of PMSCs was performed using a Luciferase-GFP-containing lentiviral vector and efficiency of transduction was tested by fluorescent microscopy and flow cytometry analysis. RESULTS We determined that an average of 2.09 × 10(6) (SD ± 8.59 × 10(5)) PMSCs could be obtained from CVS-size tissue samples within 30 d (mean = 27 d, SD ± 2.28), indicating that therapeutic numbers of cells can be rapidly expanded from very limited masses of tissue. Immunophenotyping by flow cytometry demonstrated that PMSCs were positive for MSC markers CD105, CD90, CD73, CD44, and CD29, and were negative for hematopoietic and endothelial markers CD45, CD34, and CD31. PMSCs displayed trilineage differentiation capability, and were found to express developmental transcription factors Sox10 and Sox17 as well as neural-related structural proteins NFM, Nestin, and S100β. Cytokine arrays revealed a robust and extensive profile of PMSC-secreted cytokines and growth factors, and detected 34 factors with spot density values exceeding 10(3). Detected factors had widely diverse functions that include modulation of angiogenesis and immune response, cell chemotaxis, cell proliferation, blood vessel maturation and homeostasis, modulation of insulin-like growth factor activity, neuroprotection, extracellular matrix degradation and even blood coagulation. Importantly, PMSCs were also determined to be compatible with both biological and synthetic material-based delivery vehicles such as collagen and fibrin hydrogels, and biodegradable nanofiber scaffolds made from a combination of PLA and PLGA. Finally, we demonstrated that PMSCs can be efficiently transduced (> 95%) with a Luciferase-GFP-containing lentiviral vector for future in vivo cell tracking after transplantation. CONCLUSION Our findings indicate that PMSCs represent a unique source of cells that can be effectively utilized for in utero cell therapy and tissue engineering.
Collapse
Affiliation(s)
- Lee Lankford
- Lee Lankford, Taryn Selby, James Becker, Volodymyr Ryzhuk, Connor Long, Diana Farmer, Aijun Wang, Department of Surgery, University of California, Davis Health System, Sacramento, CA 95817, United States
| | - Taryn Selby
- Lee Lankford, Taryn Selby, James Becker, Volodymyr Ryzhuk, Connor Long, Diana Farmer, Aijun Wang, Department of Surgery, University of California, Davis Health System, Sacramento, CA 95817, United States
| | - James Becker
- Lee Lankford, Taryn Selby, James Becker, Volodymyr Ryzhuk, Connor Long, Diana Farmer, Aijun Wang, Department of Surgery, University of California, Davis Health System, Sacramento, CA 95817, United States
| | - Volodymyr Ryzhuk
- Lee Lankford, Taryn Selby, James Becker, Volodymyr Ryzhuk, Connor Long, Diana Farmer, Aijun Wang, Department of Surgery, University of California, Davis Health System, Sacramento, CA 95817, United States
| | - Connor Long
- Lee Lankford, Taryn Selby, James Becker, Volodymyr Ryzhuk, Connor Long, Diana Farmer, Aijun Wang, Department of Surgery, University of California, Davis Health System, Sacramento, CA 95817, United States
| | - Diana Farmer
- Lee Lankford, Taryn Selby, James Becker, Volodymyr Ryzhuk, Connor Long, Diana Farmer, Aijun Wang, Department of Surgery, University of California, Davis Health System, Sacramento, CA 95817, United States
| | - Aijun Wang
- Lee Lankford, Taryn Selby, James Becker, Volodymyr Ryzhuk, Connor Long, Diana Farmer, Aijun Wang, Department of Surgery, University of California, Davis Health System, Sacramento, CA 95817, United States
| |
Collapse
|
|
15
|
Umbilical cord Wharton's jelly repeated culture system: a new device and method for obtaining abundant mesenchymal stem cells for bone tissue engineering. PLoS One 2014; 9:e110764. [PMID: 25329501 PMCID: PMC4203828 DOI: 10.1371/journal.pone.0110764] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2013] [Accepted: 09/24/2014] [Indexed: 01/17/2023] Open
Abstract
To date, various types of cells for seeding regenerative scaffolds have been used for bone tissue engineering. Among seed cells, the mesenchymal stem cells derived from human umbilical cord Wharton’s jelly (hUCMSCs) represent a promising candidate and hold potential for bone tissue engineering due to the the lack of ethical controversies, accessibility, sourced by non-invasive procedures for donors, a reduced risk of contamination, osteogenic differentiation capacities, and higher immunomodulatory capacity. However, the current culture methods are somewhat complicated and inefficient and often fail to make the best use of the umbilical cord (UC) tissues. Moreover, these culture processes cannot be performed on a large scale and under strict quality control. As a result, only a small quantity of cells can be harvested using the current culture methods. To solve these problems, we designed and evaluated an UC Wharton’s jelly repeated culture device. Using this device, hUCMSCs were obtained from the repeated cultures and their quantities and biological characteristics were compared. We found that using our culture device, which retained all tissue blocks on the bottom of the dish, the total number of obtained cells increased 15–20 times, and the time required for the primary passage was reduced. Moreover, cells harvested from the repeated cultures exhibited no significant difference in their immunophenotype, potential for multilineage differentiation, or proliferative, osteoinductive capacities, and final osteogenesis. The application of the repeated culture frame (RCF) not only made full use of the Wharton’s jelly but also simplified and specified the culture process, and thus, the culture efficiency was significantly improved. In summary, abundant hUCMSCs of dependable quality can be acquired using the RCF.
Collapse
|
|
16
|
Cho JS, Park JH, Kang JH, Kim SE, Park IH, Lee HM. Isolation and characterization of multipotent mesenchymal stem cells in nasal polyps. Exp Biol Med (Maywood) 2014; 240:185-93. [PMID: 25294891 DOI: 10.1177/1535370214553898] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Mesenchymal stem cells (MSCs) are multipotent progenitor cells in adult tissues. This study aimed to investigate nasal polyp (NP) tissues as a potential new source of multipotent MSCs that maintain their stemness and differentiation potential following multiple rounds of passaging. NP tissues were obtained from 10 patients during endoscopic sinus surgery. After isolating and culturing NP-derived MSCs (npMSCs), the expression levels of the surface markers CD34, CD44, CD45, CD73, CD90, CD105, CD106, CD146 and human leukocyte antigens-class II DR antigen (HLA-DR) were estimated by flow cytometry. NpMSCs were cultured in chondrogenic, osteogenic, adipogenic, or neurogenic differentiation medium. The differentiation potential of npMSCs was analyzed by Alcian blue, alizarin red S, oil red O, and immunocytochemical staining and reverse transcription-polymerase chain reaction. The clonogenic potential of npMSCs was measured using a colony-forming unit assay. Cell proliferation of npMSCs was measured using the 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay. Flow cytometry analysis revealed that npMSCs were negative for hematopoietic lineage markers (CD34, CD45, and HLA-DR) and positive for MSC markers (CD44, CD73, CD90, and CD105). The npMSCs differentiated into osteogenic, adipogenic, chondrogenic, and neurogenic lineages, respectively. Chondrogenically differentiated npMSCs were stained with Alcian blue, osteogenically differentiated npMSCs were stained with alizarin red S, and adipogenically differentiated npMSCs were stained with oil red O. Real-time polymerase chain reaction results showed that the differentiated npMSCs expressed the respective differentiation markers (Sox 9 and Col2A for chondrogenesis, Runx2 and osteocalcin for osteogenesis, fatty acid-binding protein 4 and peroxisome proliferator-activated receptor γ for adipogenesis, TuJ1, neurofilament light chain, and neurofilament heavy chain for neurogenesis). There were no significant differences in the clonogenic potential and proliferation rate between early and late passage npMSCs. These results show that npMSCs possess the characteristics of MSCs in terms of morphology, multipotent differentiation capacity, cell surface marker expression, and clonogenicity. Thus, npMSCs may represent an alternative source of MSCs.
Collapse
Affiliation(s)
- Jung-Sun Cho
- Biomedical Science, College of Medicine, Korea University, Seoul 152-703, Korea College of Medicine, Institute for Medical Devices Clinical Trial Center, Guro Hospital, Korea University, Seoul 152-703, Korea
| | - Joo-Hoo Park
- Biomedical Science, College of Medicine, Korea University, Seoul 152-703, Korea
| | - Ju-Hyung Kang
- Biomedical Science, College of Medicine, Korea University, Seoul 152-703, Korea
| | - Sung Eun Kim
- Department of Orthopedic Surgery and Rare Diseases Institute, College of Medicine, Korea University, Seoul 152-703, Korea
| | - Il-Ho Park
- College of Medicine, Institute for Medical Devices Clinical Trial Center, Guro Hospital, Korea University, Seoul 152-703, Korea Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Korea University, College of Medicine, Seoul 152-703, Korea
| | - Heung-Man Lee
- Biomedical Science, College of Medicine, Korea University, Seoul 152-703, Korea College of Medicine, Institute for Medical Devices Clinical Trial Center, Guro Hospital, Korea University, Seoul 152-703, Korea Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Korea University, College of Medicine, Seoul 152-703, Korea
| |
Collapse
|
|
17
|
Liu H, Murthi P, Qin S, Kusuma GD, Borg AJ, Knöfler M, Haslinger P, Manuelpillai U, Pertile MD, Abumaree M, Kalionis B. A novel combination of homeobox genes is expressed in mesenchymal chorionic stem/stromal cells in first trimester and term pregnancies. Reprod Sci 2014; 21:1382-94. [PMID: 24692208 DOI: 10.1177/1933719114526471] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Human chorionic mesenchymal stem/stromal cells (CMSCs) derived from the placenta are similar to adult tissue-derived MSCs. The aim of this study was to investigate the role of these cells in normal placental development. Transcription factors, particularly members of the homeobox gene family, play crucial roles in maintaining stem cell proliferation and lineage specification in embryonic tissues. In adult tissues and organs, stem cells proliferate at low levels in their niche until they receive cues from the microenvironment to differentiate. The homeobox genes that are expressed in the CMSC niche in placental tissues have not been identified. We used the novel strategy of laser capture microdissection to isolate the stromal component of first trimester villi and excluded the cytotrophoblast and syncytiotrophoblast layers that comprise the outer layer of the chorionic villi. Microarray analysis was then used to screen for homeobox genes in the microdissected tissue. Candidate homeobox genes were selected for further RNA analysis. Immunohistochemistry of candidate genes in first trimester placental villous stromal tissue revealed homeobox genes Meis1, myeloid ectropic viral integration site 1 homolog 2 (MEIS2), H2.0-like Drosophila (HLX), transforming growth factor β-induced factor (TGIF), and distal-less homeobox 5 (DLX5) were expressed in the vascular niche where CMSCs have been shown to reside. Expression of MEIS2, HLX, TGIF, and DLX5 was also detected in scattered stromal cells. Real-time polymerase chain reaction and immunocytochemistry verified expression of MEIS2, HLX, TGIF, and DLX5 homeobox genes in first trimester and term CMSCs. These data suggest a combination of regulatory homeobox genes is expressed in CMSCs from early placental development to term, which may be required for stem cell proliferation and differentiation.
Collapse
Affiliation(s)
- Haiying Liu
- Department of Obstetrics and Gynaecology, QiLu Hospital of Shandong University, Jinan, Shandong, P.R. China
| | - Padma Murthi
- Department of Obstetrics and Gynaecology, University of Melbourne, The Royal Women's Hospital, Parkville, Victoria, Australia Department of Perinatal Medicine, Pregnancy Research Centre, The Royal Women's Hospital, Parkville, Victoria, Australia
| | - Sharon Qin
- Department of Obstetrics and Gynaecology, University of Melbourne, The Royal Women's Hospital, Parkville, Victoria, Australia Department of Perinatal Medicine, Pregnancy Research Centre, The Royal Women's Hospital, Parkville, Victoria, Australia
| | - Gina D Kusuma
- Department of Obstetrics and Gynaecology, University of Melbourne, The Royal Women's Hospital, Parkville, Victoria, Australia Department of Perinatal Medicine, Pregnancy Research Centre, The Royal Women's Hospital, Parkville, Victoria, Australia
| | - Anthony J Borg
- Department of Perinatal Medicine, Pregnancy Research Centre, The Royal Women's Hospital, Parkville, Victoria, Australia
| | - Martin Knöfler
- Department of Obstetrics and Fetal-Maternal Medicine, Reproductive Biology Unit, Medical University of Vienna, Vienna, Austria
| | - Peter Haslinger
- Department of Obstetrics and Fetal-Maternal Medicine, Reproductive Biology Unit, Medical University of Vienna, Vienna, Austria
| | - Ursula Manuelpillai
- Centre for Genetic Diseases, Monash Institute of Medical Research, Monash University, Clayton, Victoria
| | - Mark D Pertile
- VCGS, Murdoch Children's Research Institute, Royal Childrens Hospital, Flemington Road, Parkville, Victoria, Australia
| | - Mohamed Abumaree
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences/ King Abdulla International Medical Research Center, Riyadh, Saudi Arabia
| | - Bill Kalionis
- Department of Obstetrics and Gynaecology, University of Melbourne, The Royal Women's Hospital, Parkville, Victoria, Australia Department of Perinatal Medicine, Pregnancy Research Centre, The Royal Women's Hospital, Parkville, Victoria, Australia
| |
Collapse
|
|
18
|
Yeh HY, Lin TY, Lin CH, Yen BL, Tsai CL, Hsu SH. Neocartilage formation from mesenchymal stem cells grown in type II collagen-hyaluronan composite scaffolds. Differentiation 2014; 86:171-83. [PMID: 24462469 DOI: 10.1016/j.diff.2013.11.001] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2013] [Revised: 11/06/2013] [Accepted: 11/07/2013] [Indexed: 12/11/2022]
Abstract
Three-dimensional (3D) collagen type II-hyaluronan (HA) composite scaffolds (CII-HA) which mimics the extracellular environment of natural cartilage were fabricated in this study. Rheological measurements demonstrated that the incorporation of HA increased the compression modulus of the scaffolds. An initial in vitro evaluation showed that scaffolds seeded with porcine chondrocytes formed cartilaginous-like tissue after 8 weeks, and HA functioned to promote the growth of chondrocytes into scaffolds. Placenta-derived multipotent cells (PDMC) and gingival fibroblasts (GF) were seeded on tissue culture polystyrene (TCPS), CII-HA films, and small intestinal submucosa (SIS) sheets for comparing their chondrogenesis differentiation potentials with those of adipose-derived adult stem cells (ADAS) and bone marrow-derived mesenchymal stem cells (BMSC). Among different cells, PDMC showed the greatest chondrogenic differentiation potential on both CII-HA films and SIS sheets upon TGF-β3 induction, followed by GF. This was evidenced by the up-regulation of chondrogenic genes (Sox9, aggrecan, and collagen type II), which was not observed for cells grown on TCPS. This finding suggested the essential role of substrate materials in the chondrogenic differentiation of PDMC and GF. Neocartilage formation was more obvious in both PDMC and GF cells plated on CII-HA composite scaffolds vs. 8-layer SIS at 28 days in vitro. Finally, implantation of PDMC/CII-HA constructs into NOD-SCID mice confirmed the formation of tissue-engineered cartilage in vivo.
Collapse
Affiliation(s)
- Hsi-Yi Yeh
- Institute of Polymer Science and Engineering, National Taiwan University, Taipei, Taiwan
| | - Ting-Yu Lin
- Institute of Polymer Science and Engineering, National Taiwan University, Taipei, Taiwan
| | - Chen-Huan Lin
- Center for Neuropsychiatry, China Medical University Hospital, Taichung, Taiwan
| | - B Linju Yen
- Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli, Taiwan
| | - Ching-Lin Tsai
- Department of Orthopaedics, National Taiwan University Hospital, Taipei, Taiwan
| | - Shan-Hui Hsu
- Institute of Polymer Science and Engineering, National Taiwan University, Taipei, Taiwan; Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan; Institute of Biomedical Engineering, National Chung Hsing University, Taichung, Taiwan.
| |
Collapse
|
|
19
|
Hart DA. Perspectives on endogenous and exogenous tissue engineering following injury to tissues of the knee. ACTA ACUST UNITED AC 2014. [DOI: 10.4236/jbise.2014.72009] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
|
|
20
|
Adipose-derived mesenchymal cells for bone regereneration: state of the art. BIOMED RESEARCH INTERNATIONAL 2013; 2013:416391. [PMID: 24307997 PMCID: PMC3838853 DOI: 10.1155/2013/416391] [Citation(s) in RCA: 61] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Download PDF] [Subscribe] [Scholar Register] [Received: 06/14/2013] [Accepted: 09/25/2013] [Indexed: 12/21/2022]
Abstract
Adipose tissue represents a hot topic in regenerative medicine because of the tissue source abundance, the relatively easy retrieval, and the inherent biological properties of mesenchymal stem cells residing in its stroma. Adipose-derived mesenchymal stem cells (ASCs) are indeed multipotent somatic stem cells exhibiting growth kinetics and plasticity, proved to induce efficient tissue regeneration in several biomedical applications. A defined consensus for their isolation, classification, and characterization has been very recently achieved. In particular, bone tissue reconstruction and regeneration based on ASCs has emerged as a promising approach to restore structure and function of bone compromised by injury or disease. ASCs have been used in combination with osteoinductive biomaterial and/or osteogenic molecules, in either static or dynamic culture systems, to improve bone regeneration in several animal models. To date, few clinical trials on ASC-based bone reconstruction have been concluded and proved effective. The aim of this review is to dissect the state of the art on ASC use in bone regenerative applications in the attempt to provide a comprehensive coverage of the topics, from the basic laboratory to recent clinical applications.
Collapse
|
|
21
|
Abstract
Orthopedic injuries are common and a source of much misery and economic stress. Several relevant tissues, such as cartilage, meniscus, and intra-articular ligaments, do not heal. And even bone, which normally regenerates spontaneously, can fail to mend. The regeneration of orthopedic tissues requires 4 key components: cells, morphogenetic signals, scaffolds, and an appropriate mechanical environment. Although differentiated cells from the tissue in question can be used, most cellular research focuses on the use of mesenchymal stem cells. These can be retrieved from many different tissues, and one unresolved question is the degree to which the origin of the cells matters. Embryonic and induced pluripotent stem cells are also under investigation. Morphogenetic signals are most frequently supplied by individual recombinant growth factors or native mixtures provided by, for example, platelet-rich plasma; mesenchymal stem cells are also a rich source of trophic factors. Obstacles to the sustained delivery of individual growth factors can be addressed by gene transfer or smart scaffolds, but we still lack detailed, necessary information on which delivery profiles are needed. Scaffolds may be based on natural products, synthetic materials, or devitalized extracellular matrix. Strategies to combine these components to regenerate tissue can follow traditional tissue engineering practices, but these are costly, cumbersome, and not well suited to treating large numbers of individuals. More expeditious approaches make full use of intrinsic biological processes in vivo to avoid the need for ex vivo expansion of autologous cells and multiple procedures. Clinical translation remains a bottleneck.
Collapse
Affiliation(s)
- Christopher H Evans
- Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA; Collaborative Research Center, AO Foundation, Davos, Switzerland.
| |
Collapse
|
|
22
|
Henkel J, Woodruff MA, Epari DR, Steck R, Glatt V, Dickinson IC, Choong PFM, Schuetz MA, Hutmacher DW. Bone Regeneration Based on Tissue Engineering Conceptions - A 21st Century Perspective. Bone Res 2013; 1:216-48. [PMID: 26273505 PMCID: PMC4472104 DOI: 10.4248/br201303002] [Citation(s) in RCA: 517] [Impact Index Per Article: 43.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2013] [Accepted: 07/20/2013] [Indexed: 12/18/2022] Open
Abstract
The role of Bone Tissue Engineering in the field of Regenerative Medicine has been the topic of substantial research over the past two decades. Technological advances have improved orthopaedic implants and surgical techniques for bone reconstruction. However, improvements in surgical techniques to reconstruct bone have been limited by the paucity of autologous materials available and donor site morbidity. Recent advances in the development of biomaterials have provided attractive alternatives to bone grafting expanding the surgical options for restoring the form and function of injured bone. Specifically, novel bioactive (second generation) biomaterials have been developed that are characterised by controlled action and reaction to the host tissue environment, whilst exhibiting controlled chemical breakdown and resorption with an ultimate replacement by regenerating tissue. Future generations of biomaterials (third generation) are designed to be not only osteoconductive but also osteoinductive, i.e. to stimulate regeneration of host tissues by combining tissue engineering and in situ tissue regeneration methods with a focus on novel applications. These techniques will lead to novel possibilities for tissue regeneration and repair. At present, tissue engineered constructs that may find future use as bone grafts for complex skeletal defects, whether from post-traumatic, degenerative, neoplastic or congenital/developmental "origin" require osseous reconstruction to ensure structural and functional integrity. Engineering functional bone using combinations of cells, scaffolds and bioactive factors is a promising strategy and a particular feature for future development in the area of hybrid materials which are able to exhibit suitable biomimetic and mechanical properties. This review will discuss the state of the art in this field and what we can expect from future generations of bone regeneration concepts.
Collapse
Affiliation(s)
- Jan Henkel
- Institute of Health & Biomedical Innovation, Queensland University of Technology , Brisbane, Queensland, Australia
| | - Maria A Woodruff
- Institute of Health & Biomedical Innovation, Queensland University of Technology , Brisbane, Queensland, Australia
| | - Devakara R Epari
- Institute of Health & Biomedical Innovation, Queensland University of Technology , Brisbane, Queensland, Australia
| | - Roland Steck
- Institute of Health & Biomedical Innovation, Queensland University of Technology , Brisbane, Queensland, Australia
| | - Vaida Glatt
- Institute of Health & Biomedical Innovation, Queensland University of Technology , Brisbane, Queensland, Australia
| | - Ian C Dickinson
- Orthopaedic Oncology Service, Princess Alexandra Hospital , Brisbane, Australia
| | - Peter F M Choong
- Department of Surgery, University of Melbourne, St. Vincent's Hospital , Melbourne, Australia ; Department of Orthopaedics, St. Vincent's Hospital , Melbourne, Australia ; Bone and Soft Tissue Sarcoma Service, Peter MacCallum Cancer Centre , Melbourne, Australia
| | - Michael A Schuetz
- Institute of Health & Biomedical Innovation, Queensland University of Technology , Brisbane, Queensland, Australia ; Orthopaedic and Trauma Services, Princess Alexandra Hospital , Brisbane, Australia
| | - Dietmar W Hutmacher
- Orthopaedic Oncology Service, Princess Alexandra Hospital , Brisbane, Australia ; George W Woodruff School of Mechanical Engineering, Georgia Institute of Technology , Atlanta, GA, USA
| |
Collapse
|
|
23
|
Nikukar H, Reid S, Tsimbouri PM, Riehle MO, Curtis ASG, Dalby MJ. Osteogenesis of mesenchymal stem cells by nanoscale mechanotransduction. ACS NANO 2013; 7:2758-67. [PMID: 23442213 DOI: 10.1021/nn400202j] [Citation(s) in RCA: 92] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/21/2023]
Abstract
It is likely that mesenchymal stem cells will find use in many autologous regenerative therapies. However, our ability to control cell stem growth and differentiation is presently limited, and this is a major hurdle to the clinical use of these multipotent cells especially when considering the desire not to use soluble factors or complex media formulations in culture. Also, the large number of cells required to be clinically useful is currently a hurdle to using materials-based (stiffness, chemistry, nanotopography, etc.) culture substrates. Here we give a first demonstration of using nanoscale sinusoidal mechanotransductive protocols (10-14 nm displacements at 1 kHz frequency), "nanokicking", to promote osteoblastogenesis in human mesenchymal stem cell cultures. On the basis of application of the reverse piezo effect, we use interferometry to develop the optimal stem cell stimulation conditions, allowing delivery of nanoscale cues across the entire surface of the Petri dishes used. A combination of immunofluorescence, PCR, and microarray has then been used to demonstrate osteoblastogenesis, and the arrays implicate RhoA as central to osteoblastic differentiation in agreement with materials-based strategies. We validate this with pharmacological inhibition of RhoA kinase. It is easy to envisage such stimulation protocols being up-scaled to form large-scale osteoblast bioreactors as standard cell culture plates and incubators are used in the protocol.
Collapse
Affiliation(s)
- Habib Nikukar
- Centre for Cell Engineering, Institute for Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, United Kingdom
| | | | | | | | | | | |
Collapse
|