Matrix from urine stem cells boosts tissue-specific stem cell mediated functional cartilage reconstruction

• Published in: Bioactive materials Vol. 23; pp. 353 - 367
• Main Authors: Pei, Ming, Pei, Yixuan Amy, Zhou, Sheng, Mikaeiliagah, Elmira, Erickson, Christopher, Giertych, Benjamin, Akhter, Halima, Wang, Lei, Stewart, Amanda, Parenti, Joshua, Wang, Bin, Wen, Sijin, Sim, Sotcheadt, Quenneville, Eric, Hansen, Kirk C., Frisch, Steven, Hu, Gangqing
• Format: Journal Article
• Language: English
• Published: China Elsevier B.V 01.05.2023; KeAi Publishing; KeAi Communications Co., Ltd
• Subjects: Decellularized extracellular matrix; Functional cartilage repair; Rejuvenation; Tissue-specific stem cell; Urine-derived stem cell; Decellularized extracellular matrix; Tissue-specific stem cell; Functional cartilage repair; Urine-derived stem cell; Rejuvenation
• ISSN: 2452-199X; 2452-199X
• DOI: 10.1016/j.bioactmat.2022.11.012

Articular cartilage has a limited capacity to self-heal once damaged. Tissue-specific stem cells are a solution for cartilage regeneration; however, ex vivo expansion resulting in cell senescence remains a challenge as a large quantity of high-quality tissue-specific stem cells are needed for cartilage regeneration. Our previous report demonstrated that decellularized extracellular matrix (dECM) deposited by human synovium-derived stem cells (SDSCs), adipose-derived stem cells (ADSCs), urine-derived stem cells (UDSCs), or dermal fibroblasts (DFs) provided an ex vivo solution to rejuvenate human SDSCs in proliferation and chondrogenic potential, particularly for dECM deposited by UDSCs. To make the cell-derived dECM (C-dECM) approach applicable clinically, in this study, we evaluated ex vivo rejuvenation of rabbit infrapatellar fat pad-derived stem cells (IPFSCs), an easily accessible alternative for SDSCs, by the abovementioned C-dECMs, in vivo application for functional cartilage repair in a rabbit osteochondral defect model, and potential cellular and molecular mechanisms underlying this rejuvenation. We found that C-dECM rejuvenation promoted rabbit IPFSCs' cartilage engineering and functional regeneration in both ex vivo and in vivo models, particularly for the dECM deposited by UDSCs, which was further confirmed by proteomics data. RNA-Seq analysis indicated that both mesenchymal-epithelial transition (MET) and inflammation-mediated macrophage activation and polarization are potentially involved in the C-dECM-mediated promotion of IPFSCs’ chondrogenic capacity, which needs further investigation. [Display omitted] •dECM expansion promoted IPFSCs' proliferation and chondrogenic potential.•UECM-preconditioned IPFSCs contributed to functional cartilage reconstruction.•The medial condyle displayed lower instantaneous modulus than the lateral condyle.•Macrophage transition is involved in dECM-mediated IPFSCs' rejuvenation.•dECM expansion modulates IPFSCs' MET/EMT signals.