TY - JOUR
T1 - Cartilage from human-induced pluripotent stem cells
T2 - comparison with neo-cartilage from chondrocytes and bone marrow mesenchymal stromal cells
AU - Rodríguez Ruiz, Alejandro
AU - Dicks, Amanda
AU - Tuerlings, Margo
AU - Schepers, Koen
AU - van Pel, Melissa
AU - Nelissen, Rob G.H.H.
AU - Freund, Christian
AU - Mummery, Christine L.
AU - Orlova, Valeria
AU - Guilak, Farshid
AU - Meulenbelt, Ingrid
AU - Ramos, Yolande F.M.
N1 - Funding Information:
Research leading to these results has received funding from the Dutch Arthritis Society (DAF-16–1-406), the Dutch Scientific Research council NWO/ZonMW VICI scheme (nr 91816631/528), the National Institutes of Health grants AG15768 and AG46927, and from the European Union’s Horizon 2020 research and innovation program (No 874671; the material presented and views expressed here are the responsibility of the authors only; the EU Commission takes no responsibility for any use made of the information set out).
Funding Information:
The Leiden University Medical Centre has and is supporting the RAAK study, and we thank all study participants of the RAAK study. We thank Evelyn Houtman, Enrike van der Linden, Robert van der Wal, Peter van Schie, Shaho Hasan, Maartje Meijer, Daisy Latijnhouwers, Anika Rabelink-Hoogenstraaten, and Geert Spierenburg for their contribution to the collection of the joint tissues. We thank all the members of the Molecular Epidemiology Osteoarthritis group for their valuable discussion and feedback. Data is generated within the scope of the Medical Delta programs Regenerative Medicine 4D (?Generating complex tissues with stem cells and printing technology and Improving Mobility with Technology?).
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/11
Y1 - 2021/11
N2 - Cartilage has little intrinsic capacity for repair, so transplantation of exogenous cartilage cells is considered a realistic option for cartilage regeneration. We explored whether human-induced pluripotent stem cells (hiPSCs) could represent such unlimited cell sources for neo-cartilage comparable to human primary articular chondrocytes (hPACs) or human bone marrow-derived mesenchymal stromal cells (hBMSCs). For this, chondroprogenitor cells (hiCPCs) and hiPSC-derived mesenchymal stromal cells (hiMSCs) were generated from two independent hiPSC lines and characterized by morphology, flow cytometry, and differentiation potential. Chondrogenesis was compared to hBMSCs and hPACs by histology, immunohistochemistry, and RT-qPCR, while similarities were estimated based on Pearson correlations using a panel of 20 relevant genes. Our data show successful differentiations of hiPSC into hiMSCs and hiCPCs. Characteristic hBMSC markers were shared between hBMSCs and hiMSCs, with the exception of CD146 and CD45. However, neo-cartilage generated from hiMSCs showed low resemblances when compared to hBMSCs (53%) and hPACs (39%) characterized by lower collagen type 2 and higher collagen type 1 expression. Contrarily, hiCPC neo-cartilage generated neo-cartilage more similar to hPACs (65%), with stronger expression of matrix deposition markers. Our study shows that taking a stepwise approach to generate neo-cartilage from hiPSCs via chondroprogenitor cells results in strong similarities to neo-cartilage of hPACs within 3 weeks following chondrogenesis, making them a potential candidate for regenerative therapies. Contrarily, neo-cartilage deposited by hiMSCs seems more prone to hypertrophic characteristics compared to hPACs. We therefore compared chondrocytes derived from hiMSCs and hiCPCs with hPACs and hBMSCs to outline similarities and differences between their neo-cartilage and establish their potential suitability for regenerative medicine and disease modelling.
AB - Cartilage has little intrinsic capacity for repair, so transplantation of exogenous cartilage cells is considered a realistic option for cartilage regeneration. We explored whether human-induced pluripotent stem cells (hiPSCs) could represent such unlimited cell sources for neo-cartilage comparable to human primary articular chondrocytes (hPACs) or human bone marrow-derived mesenchymal stromal cells (hBMSCs). For this, chondroprogenitor cells (hiCPCs) and hiPSC-derived mesenchymal stromal cells (hiMSCs) were generated from two independent hiPSC lines and characterized by morphology, flow cytometry, and differentiation potential. Chondrogenesis was compared to hBMSCs and hPACs by histology, immunohistochemistry, and RT-qPCR, while similarities were estimated based on Pearson correlations using a panel of 20 relevant genes. Our data show successful differentiations of hiPSC into hiMSCs and hiCPCs. Characteristic hBMSC markers were shared between hBMSCs and hiMSCs, with the exception of CD146 and CD45. However, neo-cartilage generated from hiMSCs showed low resemblances when compared to hBMSCs (53%) and hPACs (39%) characterized by lower collagen type 2 and higher collagen type 1 expression. Contrarily, hiCPC neo-cartilage generated neo-cartilage more similar to hPACs (65%), with stronger expression of matrix deposition markers. Our study shows that taking a stepwise approach to generate neo-cartilage from hiPSCs via chondroprogenitor cells results in strong similarities to neo-cartilage of hPACs within 3 weeks following chondrogenesis, making them a potential candidate for regenerative therapies. Contrarily, neo-cartilage deposited by hiMSCs seems more prone to hypertrophic characteristics compared to hPACs. We therefore compared chondrocytes derived from hiMSCs and hiCPCs with hPACs and hBMSCs to outline similarities and differences between their neo-cartilage and establish their potential suitability for regenerative medicine and disease modelling.
KW - Chondrogenesis
KW - Chondroprogenitor
KW - Mesenchymal stromal cells
KW - Neo-cartilage
KW - Tissue regeneration
KW - hiPSCs
UR - http://www.scopus.com/inward/record.url?scp=85110321981&partnerID=8YFLogxK
U2 - 10.1007/s00441-021-03498-5
DO - 10.1007/s00441-021-03498-5
M3 - Article
C2 - 34241697
AN - SCOPUS:85110321981
SN - 0302-766X
VL - 386
SP - 309
EP - 320
JO - Cell and Tissue Research
JF - Cell and Tissue Research
IS - 2
ER -