Cartilage from human-induced pluripotent stem cells: comparison with neo-cartilage from chondrocytes and bone marrow mesenchymal stromal cells.


Journal

Cell and tissue research
ISSN: 1432-0878
Titre abrégé: Cell Tissue Res
Pays: Germany
ID NLM: 0417625

Informations de publication

Date de publication:
Nov 2021
Historique:
received: 03 03 2021
accepted: 23 06 2021
pubmed: 10 7 2021
medline: 11 2 2022
entrez: 9 7 2021
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 34241697
doi: 10.1007/s00441-021-03498-5
pii: 10.1007/s00441-021-03498-5
pmc: PMC8557148
doi:

Types de publication

Comparative Study Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

309-320

Subventions

Organisme : ReumaNederland
ID : DAF-16-1-406
Organisme : NIA NIH HHS
ID : R01 AG046927
Pays : United States
Organisme : NIH HHS
ID : AG15768
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG015768
Pays : United States
Organisme : NWO/ZonMW VICI
ID : 91816631/528
Organisme : NIH HHS
ID : AG46927
Pays : United States
Organisme : European Union's Horizon 2020
ID : 874671

Informations de copyright

© 2021. The Author(s).

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Auteurs

Alejandro Rodríguez Ruiz (A)

Dept. of Biomedical Data Sciences, Section Molecular Epidemiology, Leiden University Medical Center, LUMC, Leiden, The Netherlands.

Amanda Dicks (A)

Dept. Orthopedic Surgery, Washington University and Shriners Hospitals for Children, St. Louis, USA.

Margo Tuerlings (M)

Dept. of Biomedical Data Sciences, Section Molecular Epidemiology, Leiden University Medical Center, LUMC, Leiden, The Netherlands.

Koen Schepers (K)

Dept. Immunohematology and Blood Transfusion, LUMC, Leiden, The Netherlands.

Melissa van Pel (M)

Dept. Immunohematology and Blood Transfusion, LUMC, Leiden, The Netherlands.
NECSTGEN, Leiden, The Netherlands.

Rob G H H Nelissen (RGHH)

Dept. Orthopaedics, LUMC, Leiden, The Netherlands.

Christian Freund (C)

Dept. Anatomy and Embryology, LUMC, Leiden, The Netherlands.
LUMC hiPSC Hotel, Leiden, The Netherlands.

Christine L Mummery (CL)

Dept. Anatomy and Embryology, LUMC, Leiden, The Netherlands.
LUMC hiPSC Hotel, Leiden, The Netherlands.

Valeria Orlova (V)

Dept. Anatomy and Embryology, LUMC, Leiden, The Netherlands.

Farshid Guilak (F)

Dept. Orthopedic Surgery, Washington University and Shriners Hospitals for Children, St. Louis, USA.

Ingrid Meulenbelt (I)

Dept. of Biomedical Data Sciences, Section Molecular Epidemiology, Leiden University Medical Center, LUMC, Leiden, The Netherlands.

Yolande F M Ramos (YFM)

Dept. of Biomedical Data Sciences, Section Molecular Epidemiology, Leiden University Medical Center, LUMC, Leiden, The Netherlands. y.f.m.ramos@lumc.nl.

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