Divergence in chondrogenic potential between in vitro and in vivo of adipose- and synovial-stem cells from mouse and human

Stem Cell Research & Therapy

Shinsaku Tsuji¹  Ryota Chijimatsu²  Gensuke Okamura³  Shuji Taketomi⁴  Kohei Kawaguchi⁴  Junya Miyahara⁴  Hisatoshi Ishikura⁴  Junya Higuchi⁴  Sakae Tanaka⁴  Kentaro Takagi⁴  Satoshi Miwa⁴  Yuji Maenohara⁴  Keiu Nakazato⁴  Hiroshi Inui⁴  Ryota Yamagami⁴  Taku Saito⁴  Naohiro Tachibana⁴  Shin Sameshima⁴ 

[1] Avenue Cell Clinic, Tokyo, Japan;Bone and Cartilage Regenerative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan;Orthopaedic Surgery, Osaka Rosai Hospital, Osaka, Japan;Sensory and Motor System Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan;

关键词: Chondrogenesis;    Stem cell transplantation,;    Transforming growth factor β (TGF-β);    Adipose stem cells;    Synovial stem cells;    Somatic stem cells;   

DOI  :  10.1186/s13287-021-02485-5

来源: Springer

【 摘 要 】

BackgroundSomatic stem cell transplantation has been performed for cartilage injury, but the reparative mechanisms are still conflicting. The chondrogenic potential of stem cells are thought as promising features for cartilage therapy; however, the correlation between their potential for chondrogenesis in vitro and in vivo remains undefined. The purpose of this study was to investigate the intrinsic chondrogenic condition depends on cell types and explore an indicator to select useful stem cells for cartilage regeneration.MethodsThe chondrogenic potential of two different stem cell types derived from adipose tissue (ASCs) and synovium (SSCs) of mice and humans was assessed using bone morphogenic protein-2 (BMP2) and transforming growth factor-β1 (TGFβ1). Their in vivo chondrogenic potential was validated through transplantation into a mouse osteochondral defect model.ResultsAll cell types showed apparent chondrogenesis under the combination of BMP2 and TGFβ1 in vitro, as assessed by the formation of proteoglycan- and type 2 collagen (COL2)-rich tissues. However, our results vastly differed with those observed following single stimulation among species and cell types; apparent chondrogenesis of mouse SSCs was observed with supplementation of BMP2 or TGFβ1, whereas chondrogenesis of mouse ASCs and human SSCs was observed with supplementation of BMP2 not TGFβ1. Human ASCs showed no obvious chondrogenesis following single stimulation. Mouse SSCs showed the formation of hyaline-like cartilage which had less fibrous components (COL1/3) with supplementation of TGFβ1. However, human cells developed COL1/3+ tissues with all treatments. Transcriptomic analysis for TGFβ receptors and ligands of cells prior to chondrogenic induction did not indicate their distinct reactivity to the TGFβ1 or BMP2. In the transplanted site in vivo, mouse SSCs formed hyaline-like cartilage (proteoglycan+/COL2+/COL1−/COL3−) but other cell types mainly formed COL1/3-positive fibrous tissues in line with in vitro reactivity to TGFβ1.ConclusionOptimal chondrogenic factors driving chondrogenesis from somatic stem cells are intrinsically distinct among cell types and species. Among them, the response to TGFβ1 may possibly represent the fate of stem cells when locally transplanted into cartilage defects.

【 授权许可】

CC BY