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      Chondrogenic priming of human fetal synovium-derived stem cells in an adult stem cell matrix microenvironment

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          Abstract

          Cartilage defects are a challenge to treat clinically due to the avascular nature of cartilage. Low immunogenicity and extensive proliferation and multidifferentiation potential make fetal stem cells a promising source for regenerative medicine. In this study, we aimed to determine whether fetal synovium-derived stem cells (FSDSCs) exhibited replicative senescence and whether expansion on decellularized extracellular matrix (dECM) deposited by adult SDSCs (AECM) promoted FSDSCs' chondrogenic potential. FSDSCs from passage 2 and 9 were compared for chondrogenic potential, using Alcian blue staining for sulfated glycosaminoglycans (GAGs), biochemical analysis for DNA and GAG amounts, and real-time PCR for chondrogenic genes including ACAN and COL2A1. Passage 3 FSDSCs were expanded for one passage on plastic flasks (PL), AECM, or dECM deposited by fetal SDSCs (FECM). During expansion, cell proliferation was evaluated using flow cytometry for proliferation index, stem cell surface markers, and resistance to hydrogen peroxide. During chondrogenic induction, expanded FSDSCs were evaluated for tri-lineage differentiation capacity. We found that cell expansion enhanced FSDSCs' chondrogenic potential at least up to passage 9. Expansion on dECMs promoted FSDSCs' proliferative and survival capacity and adipogenic differentiation but not osteogenic capacity. AECM-primed FSDSCs exhibited an enhanced chondrogenic potential.

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          Human first-trimester fetal MSC express pluripotency markers and grow faster and have longer telomeres than adult MSC.

          Pascale Guillot, Cecilia Götherström, Jerry K.Y. Chan … (2007)
          The biological properties of stem cells are key to the success of cell therapy, for which MSC are promising candidates. Although most therapeutic applications to date have used adult bone marrow MSC, increasing evidence suggests that MSC from neonatal and mid-gestational fetal tissues are more plastic and grow faster. Fetal stem cells have been isolated earlier in development, from first-trimester blood and hemopoietic organs, raising the question of whether they are biologically closer to embryonic stem cells and thus have advantages over adult bone marrow MSC. In this study, we show that human first-trimester fetal blood, liver, and bone marrow MSC but not adult MSC express the pluripotency stem cell markers Oct-4, Nanog, Rex-1, SSEA-3, SSEA-4, Tra-1-60, and Tra-1-81. In addition, fetal MSC, irrespective of source, had longer telomeres (p < .001), had greater telomerase activity (p < .01), and expressed more human telomerase reverse transcriptase (p < .01). Fetal MSC were also more readily expandable and senesced later in culture than their adult counterparts (p < .01). Compared with adult MSC, first-trimester fetal tissues constitute a source of MSC with characteristics that appear advantageous for cell therapy.
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            Fetal mesenchymal stem-cell engraftment in bone after in utero transplantation in a patient with severe osteogenesis imperfecta.

            Olle Ringden, Katarina Le Blanc, Robert McMahon … (2005)
            Mesenchymal stem cells (MSC) are progenitors of mesenchymal tissues such as bone, cartilage, and adipose. Adult human leukocyte antigen (HLA)-matched MSC have been used in cellular therapies of bone disorders such as osteogenesis imperfecta, with promising results. A female fetus with multiple intrauterine fractures, diagnosed as severe osteogenesis imperfecta, underwent transplantation with allogeneic HLA-mismatched male fetal MSC in the 32nd week of gestation. Engraftment analyses of donor cells, immunologic reaction against donor cells, and the well-being of the patient were assessed. At 9 months of age, on slides stained for osteocalcin or osteopontin, a centromeric XY-specific probe revealed 0.3% of XY-positive cells in a bone biopsy specimen. Whole Y genome fluorescent in situ hybridization staining showed a median of 7.4% Y-positive cells (range, 6.8%-16.6%). Bone histology showed regularly arranged and configurated bone trabeculae. Patient lymphocyte proliferation against donor MSC was not observed in co-culture experiments performed in vitro after MSC injection. Complementary bisphosphonate treatment was begun at 4 months. During the first 2 years of life, three fractures were noted. At 2 years of corrected age, psychomotor development was normal and growth followed the same channel, -5 SD. The authors' findings show that allogeneic fetal MSC can engraft and differentiate into bone in a human fetus even when the recipient is immunocompetent and HLA-incompatible.
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              Concise review: the clinical application of mesenchymal stem cells for musculoskeletal regeneration: current status and perspectives.

              J. Tuan, Fabian Gilbert, Andre F. Steinert … (2012)
              Regenerative therapies in the musculoskeletal system are based on the suitable application of cells, biomaterials, and/or factors. For an effective approach, numerous aspects have to be taken into consideration, including age, disease, target tissue, and several environmental factors. Significant research efforts have been undertaken in the last decade to develop specific cell-based therapies, and in particular adult multipotent mesenchymal stem cells hold great promise for such regenerative strategies. Clinical translation of such therapies, however, remains a work in progress. In the clinical arena, autologous cells have been harvested, processed, and readministered according to protocols distinct for the target application. As outlined in this review, such applications range from simple single-step approaches, such as direct injection of unprocessed or concentrated blood or bone marrow aspirates, to fabrication of engineered constructs by seeding of natural or synthetic scaffolds with cells, which were released from autologous tissues and propagated under good manufacturing practice conditions (for example, autologous chondrocyte implantation). However, only relatively few of these cell-based approaches have entered the clinic, and none of these treatments has become a "standard of care" treatment for an orthopaedic disease to date. The multifaceted reasons for the current status from the medical, research, and regulatory perspectives are discussed here. In summary, this review presents the scientific background, current state, and implications of clinical mesenchymal stem cell application in the musculoskeletal system and provides perspectives for future developments.
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                Author and article information

                Contributors
                Ming Pei
                Journal
                Journal ID (nlm-ta): Genes Dis
                Journal ID (iso-abbrev): Genes Dis
                Title: Genes & Diseases
                Publisher: Chongqing Medical University
                ISSN (Print): 2352-4820
                ISSN (Electronic): 2352-3042
                Publication date PMC-release: 08 July 2015
                Publication date Collection: December 2015
                Publication date (Electronic): 08 July 2015
                Volume: 2
                Issue: 4
                Pages: 337-346
                Affiliations
                [a ]Stem Cell and Tissue Engineering Laboratory, Department of Orthopaedics, West Virginia University, Morgantown, WV 26506, USA
                [b ]Division of Exercise Physiology, West Virginia University, Morgantown, WV 26506, USA
                [c ]Orthopaedic Institute, Soochow University, Suzhou 215007, China
                Author notes
                [∗ ] Corresponding author. Stem Cell and Tissue Engineering Laboratory, Department of Orthopaedics, West Virginia University, PO Box 9196, One Medical Center Drive, Morgantown, WV 26506-9196, USA. Tel.: +1 304 293 1072; fax: +1 304 293 7070. mpei@ 123456hsc.wvu.edu
                Article
                Publisher ID: S2352-3042(15)00042-2
                DOI: 10.1016/j.gendis.2015.06.004
                PMC ID: 6147170
                SO-VID: e989e495-007f-4974-90bd-c24f81809e5a
                Copyright © Copyright © 2015, Chongqing Medical University. Production and hosting by Elsevier B.V.
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Date received : 5 June 2015
                Date accepted : 29 June 2015
                Categories
                Subject: Article

                Keywords: chondrogenesis,decellularized extracellular matrix,fetal stem cell,in vitro microenvironment,replicative senescence,synovium-derived stem cell
                Data availability:
                Keywords: chondrogenesis, decellularized extracellular matrix, fetal stem cell, in vitro microenvironment, replicative senescence, synovium-derived stem cell

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