Progenitor Cells in Healthy and Osteoarthritic Human Cartilage Have Extensive Culture Expansion Capacity while Retaining Chondrogenic Properties
Rikkers, M; Korpershoek, J V; Levato, R; Malda, J; Vonk, L A
(2021) Cartilage, volume 13, issue 2_suppl, pp. 129S - 142S
(Article)
Abstract
OBJECTIVE: Articular cartilage-derived progenitor cells (ACPCs) are a potential new cell source for cartilage repair. This study aims to characterize endogenous ACPCs from healthy and osteoarthritic (OA) cartilage, evaluate their potential for cartilage regeneration, and compare this to cartilage formation by chondrocytes. DESIGN: ACPCs were isolated from full-thickness healthy and
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OA human cartilage and separated from the total cell population by clonal growth after differential adhesion to fibronectin. ACPCs were characterized by growth kinetics, multilineage differentiation, and surface marker expression. Chondrogenic redifferentiation of ACPCs was compared with chondrocytes in pellet cultures. Pellets were assessed for cartilage-like matrix production by (immuno)histochemistry, quantitative analyses for glycosaminoglycans and DNA content, and expression of chondrogenic and hypertrophic genes. RESULTS: Healthy and OA ACPCs were successfully differentiated toward the adipogenic and chondrogenic lineage, but failed to produce calcified matrix when exposed to osteogenic induction media. Both ACPC populations met the criteria for cell surface marker expression of mesenchymal stromal cells (MSCs). Healthy ACPCs cultured in pellets deposited extracellular matrix containing proteoglycans and type II collagen, devoid of type I collagen. Gene expression of hypertrophic marker type X collagen was lower in healthy ACPC pellets compared with OA pellets. CONCLUSIONS: This study provides further insight into the ACPC population in healthy and OA human articular cartilage. ACPCs show similarities to MSCs, yet do not produce calcified matrix under well-established osteogenic culture conditions. Due to extensive proliferative potential and chondrogenic capacity, ACPCs show potential for cartilage regeneration and possibly for clinical application, as a promising alternative to MSCs or chondrocytes.
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Keywords: articular cartilage, cartilage repair, endogenous, osteoarthritis, progenitor cell, Immunology and Allergy, Biomedical Engineering, Physical Therapy, Sports Therapy and Rehabilitation
ISSN: 1947-6035
Publisher: SAGE Publications Inc.
Note: Funding Information: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work is supported by the partners of Regenerative Medicine Crossing Borders (RegMed XB), a public-private partnership that uses regenerative medicine strategies to cure common chronic diseases. This collaboration project is financed by the Dutch Ministry of Economic Affairs by means of the PPP Allowance made available by the Top Sector Life Sciences & Health to stimulate public-private partnerships. The research was also supported by the Dutch Arthritis Foundation (LLP-12 and LLP-22). J.V.K. and L.V. acknowledge ZonMw (The Netherlands Organization for Health Research and Development) and the strategic theme “Regenerative Medicine & Stem Cells” of the University Medical Center Utrecht. R.L. acknowledges funding from the European Research Council (Grant Agreement No. 949806), and the Horizon 2020 Research and Innovation Program under the Grant Agreement No. 814444 (MEFISTO). Funding Information: The antibody against type II collagen, developed by T. F. Linsenmayer, was obtained from the Developmental Studies Hybridoma Bank, created by the NICHD and maintained at The University of Iowa, Department of Biology, Iowa City, IA, United States. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work is supported by the partners of Regenerative Medicine Crossing Borders (RegMed XB), a public-private partnership that uses regenerative medicine strategies to cure common chronic diseases. This collaboration project is financed by the Dutch Ministry of Economic Affairs by means of the PPP Allowance made available by the Top Sector Life Sciences & Health to stimulate public-private partnerships. The research was also supported by the Dutch Arthritis Foundation (LLP-12 and LLP-22). J.V.K. and L.V. acknowledge ZonMw (The Netherlands Organization for Health Research and Development) and the strategic theme ?Regenerative Medicine & Stem Cells? of the University Medical Center Utrecht. R.L. acknowledges funding from the European Research Council (Grant Agreement No. 949806), and the Horizon 2020 Research and Innovation Program under the Grant Agreement No. 814444 (MEFISTO). Publisher Copyright: © The Author(s) 2021.
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