Articular Tissue-Mimicking Organoids Derived from Mesenchymal Stem Cells and Induced Pluripotent Stem Cells

Author:

Li Zhong AlanORCID,Shang Jiangyinzi,Xiang Shiqi,Li Eileen N.,Yagi Haruyo,Riewruja Kanyakorn,Lin Hang,Tuan Rocky S.ORCID

Abstract

Organoids offer a promising strategy for articular tissue regeneration, joint disease modeling, and development of precision medicine. In this study, two types of human stem cells—primary mesenchymal stem cells (MSCs) and induced pluripotent stem cells (iPSCs)—were employed to engineer organoids that mimicked bone, cartilage and adipose tissue, three key tissue components in articular joints. Prior to organoidogenesis, the iPSCs were first induced into mesenchymal progenitor cells (iMPCs). After characterizing the MSCs and iMPCs, they were used to generate cell-embedded extracellular matrix (ECM) constructs, which then underwent self-aggregation and lineage-specific differentiation in different induction media. Hydroxyapatite nanorods, an osteoinductive bioceramic, were leveraged to generate bone and osteochondral organoids, which effectively enhanced mineralization. The phenotypes of the generated organoids were confirmed on the basis of gene expression profiling and histology. Our findings demonstrate the feasibility and potential of generating articular tissue-recapitulating organoids from MSCs and iPSCs.

Funder

Department of Orthopaedic Surgery at the University of Pittsburgh School of Medicine

Lee Quo Wei and Lee Yik Hoi Lun Professorship in Tissue Engineering and Regenerative Medicine of The Chinese University of Hong Kong

Centre for Neuromusculoskeletal Restorative Medicine of the InnoHK Cluster

Publisher

MDPI AG

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