M Rikkers1, J V Korpershoek1, R Levato1,2, J Malda1,2, L A Vonk1,3. 1. Department of Orthopaedics, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands. 2. Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands. 3. CO.DON AG, Teltow, Germany.
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 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.
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 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.
Authors: Dongrim Seol; Daniel J McCabe; Hyeonghun Choe; Hongjun Zheng; Yin Yu; Keewoong Jang; Morgan W Walter; Abigail D Lehman; Lei Ding; Joseph A Buckwalter; James A Martin Journal: Arthritis Rheum Date: 2012-11
Authors: Riccardo Levato; William R Webb; Iris A Otto; Anneloes Mensinga; Yadan Zhang; Mattie van Rijen; René van Weeren; Ilyas M Khan; Jos Malda Journal: Acta Biomater Date: 2017-08-04 Impact factor: 8.947
Authors: Jay R Ebert; William B Robertson; Jennifer Woodhouse; Michael Fallon; M H Zheng; Timothy Ackland; David J Wood Journal: Am J Sports Med Date: 2011-01-21 Impact factor: 6.202
Authors: Philipp Niemeyer; Volker Laute; Thilo John; Christoph Becher; Peter Diehl; Thomas Kolombe; Jakob Fay; Rainer Siebold; Milan Niks; Stefan Fickert; Wolfgang Zinser Journal: Am J Sports Med Date: 2016-05-20 Impact factor: 6.202
Authors: Lucienne A Vonk; Tommy S de Windt; Ineke C M Slaper-Cortenbach; Daniël B F Saris Journal: Stem Cell Res Ther Date: 2015-05-15 Impact factor: 6.832
Authors: Iris A Otto; Paulina Nuñez Bernal; Margot Rikkers; Mattie H P van Rijen; Anneloes Mensinga; Moshe Kon; Corstiaan C Breugem; Riccardo Levato; Jos Malda Journal: iScience Date: 2022-08-18