University of California, Davis, School of Medicine, Department of Dermatology, One Shields Ave, Davis, CA 95616, USA.
FASEB J. 2011 Jan;25(1):122-31. doi: 10.1096/fj.09-148775. Epub 2010 Sep 16.
Bone marrow-derived human mesenchymal stem cells (hMSCs) possess multipotent differentiation capabilities and are a potent source of paracrine factors. We show how the epidermal keratinocyte can direct hMSC differentiation selectively. Keratinocytes and hMSCs were either cocultured in physical contact (contact cocultures), or separated without physical contact using a transwell insert (noncontact cocultures). We also delivered hMSCs into an ex vivo human excisional wound where subpopulations of the hMSCs were either in contact or were physically separated from the epidermal keratinocytes. In comparison to control hMSCs that were not cocultured, contact cocultured hMSCs adopted an epithelial morphology and expressed keratinocyte markers while noncontact cocultured hMSCs, surprisingly, adopted phenotypes that resembled myofibroblast and early neural lineage, both of which are of dermal origin. Cell fusion was not a requirement in in vitro contact cocultures, as determined by fluorescence-activated cell sorting (FACS) and fluorescence in situ hybridization analysis (FISH). To the best of our knowledge, this work provides the first example of hMSC differentiation into different lineages depending on their proximity to a single cell type.
骨髓来源的人间质干细胞（hMSCs）具有多能分化能力，是旁分泌因子的有效来源。我们展示了表皮角质形成细胞如何选择性地指导 hMSC 分化。角质形成细胞和 hMSCs 要么在物理接触下共培养（接触共培养），要么使用 Transwell 插入物在没有物理接触的情况下分离（非接触共培养）。我们还将 hMSCs 递送到体外人切除性伤口中，其中 hMSC 的亚群与表皮角质形成细胞接触或物理分离。与未共培养的对照 hMSCs 相比，接触共培养的 hMSCs 采用上皮形态并表达角质形成细胞标志物，而令人惊讶的是，非接触共培养的 hMSCs 采用的表型类似于成肌纤维细胞和早期神经谱系，这两者均来源于真皮。通过荧光激活细胞分选（FACS）和荧光原位杂交分析（FISH），确定体外接触共培养不是细胞融合的必需条件。据我们所知，这项工作首次提供了 hMSC 根据其与单一细胞类型的接近程度分化为不同谱系的示例。
