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

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-beta 1 (TGF beta 1). 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 TGF beta 1 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 TGF beta 1, whereas chondrogenesis of mouse ASCs and human SSCs was observed with supplementation of BMP2 not TGF beta 1. 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 TGF beta 1. However, human cells developed COL1/3+ tissues with all treatments. Transcriptomic analysis for TGF beta receptors and ligands of cells prior to chondrogenic induction did not indicate their distinct reactivity to the TGF beta 1 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 TGF beta 1.ConclusionOptimal chondrogenic factors driving chondrogenesis from somatic stem cells are intrinsically distinct among cell types and species. Among them, the response to TGF beta 1 may possibly represent the fate of stem cells when locally transplanted into cartilage defects.

Automated summary

This study investigated the chondrogenic potential of stem cells derived from adipose tissue and synovium, showing intrinsic differences in chondrogenic factors among cell types and species. The response to TGF beta 1 may play a crucial role in determining the fate of stem cells transplanted into cartilage defects.