Table_2_Predicting and Promoting Human Bone Marrow MSC Chondrogenesis by Way of TGFβ Receptor Profiles: Toward Personalized Medicine.docx

The use of human mesenchymal stromal cells (hMSCs) for cartilage regeneration has been hampered by the inherent donor variation of primary monolayer expanded cells. Although CD markers are typically used to characterize cell populations, there is no correlation between CD marker profile and functional outcomes. Therefore, we aimed to discover novel predictive MSC chondrogenesis markers. The chondrogenic potential of primary human bone marrow MSCs (hBMSCs) over multiple passages was assessed by standard pellet culture. We confirmed that the ratio of TGFβ-RI/TGFβ-RII at the time of cell recovery from the tissue culture plastic reliably predicted chondrogenic potential. Furthermore, it is possible to prospectively characterize any human BMSC cell population as responders or non-responders with respect to chondrogenic differentiation potential. Transient increase of the ratio with siRNA knockdown of TGFβ-RII reproducibly recovered the chondrogenic differentiation ability of non-responsive MSCs. Together this offers an opportunity to produce a more functionally characterized cell population for use in autologous cartilage repair therapies.

人间质基质细胞（human mesenchymal stromal cells，hMSCs）用于软骨再生的应用，因原代单层扩增细胞固有的供体差异而受到阻碍。尽管CD标记（CD markers）通常被用于表征细胞群，但CD标记谱与细胞功能结局之间并无关联。因此，本研究旨在发掘全新的预测性MSC软骨生成标记物。本研究通过标准微团培养法，对多代次原代人骨髓间充质基质细胞（human bone marrow MSCs，hBMSCs）的软骨生成潜能进行了评估。研究证实，从细胞培养塑料表面回收细胞时的转化生长因子βⅠ型受体（TGFβ-RI）/转化生长因子βⅡ型受体（TGFβ-RII）比值，可稳定预测细胞的软骨生成潜能。此外，针对软骨分化潜能，可前瞻性地将任意人骨髓MSC细胞群划分为反应型与非反应型。通过小干扰RNA（small interfering RNA，siRNA）敲低TGFβ-RII以瞬时升高该比值，可重复恢复非反应型MSC的软骨分化能力。综上，本研究为制备功能表征更完善的细胞群以用于自体软骨修复治疗提供了新的契机。