成体骨髓源多能间充质干细胞体内分化皮肤干细胞和皮肤组织

ADULT BONE MARROW-DERIVED PLURIPOTENTIAL MESENCHYMAL STEM CELLS GIVE RISE TO SKIN CELLS AND REGENERATE SKIN TISSUE

近年来,因在退行性或遗传性等疾病中潜在的治疗前景,成体干细胞可塑性引起众多学者的广泛兴趣。有许多报道显示骨髓源干细胞植入体内可生成多种组织细胞,但到目前为止,成体干细胞可塑性尚存争议,尤其是关于成体干细胞体内分化成皮肤组织的报道较少且意见不一。本工作,自成年BALB/C小鼠的骨髓中分离获得并体外培养扩增多能间充质干细胞,将适量的供体BALB/C小鼠骨髓源多能间充质干细胞和一定量的C57BL/小鼠骨髓细胞经尾静脉共同植入经致死量照射的成年C57BL/6小鼠。40天后,观察到受体C57BL/6小鼠背部出现白色毛发,逐渐扩展至3-4cm2,同时还出现在颈部和腹部,取该部位的皮肤组织进行免疫组化检测及RT-PCR检测。蛋白水平和基因水平的结果均显示受体C57BL/6小鼠出现白色毛发处的皮肤组织为BALB/C来源。首次直接证明了成体骨髓源多能间充质干细胞体内在一定条件下可以分化成皮肤干细胞及皮肤组织。不仅为研究体内诱导皮肤分化的机制也为鉴定成体多能干细胞提供了一个模型,也为成体干细胞可塑性理论提供了新的依据。

Recently stem cell plasticity has arouse great interests in stem cell research for its potential therapeutic application in degenerative or inherited diseases. Transplantation of bone marrow-derived stem cells in vivo has been shown to give rise to cells of muscle,liver,nerve,endothelium,epithelium etc. But there are still disputes as to stem cell plasticity, as is in the case of contribution of bone marrow-derived cell to skin cells. Here we show that cells co-purified from bone marrow mesenchymal stem cells can evidently give rise to skin tissue in vivo. In the present study , we first isolated and expanded bone marrow-derived multipotentianl mesenchymal stem cells from BALB/C mice(H-2Kd, white hair), then co-transplanted them with certain bone marrow cells from C57BL/6 mice via tail vein into lethally-irradiated 12 weeks old C57BL/6 mice(H-2Kb,black hair).The recipient mice grew out white hair on the back about forty days later. Then the area of these white hair gradually increase to 3×4cm2 and spread to abdomen and neck. We demonstrated that the majority of skin tissue within white hair region was composed of donor derived H-2Kd cells, including stem cells and mature cells by im-munohistochemistry staining. Skin cells cultured from white hair skin were proved to be almost donor origination by both irnmunohistochemistry staining and RT-PCR. Our findings provide direct evidence that bone marrow-derived cells can give rise to functional skin cells and regenerate skin tissue, also establish a model useful not only for ultimately finding out environmental cues inducing differentiation of skin cells, but also for evaluating pluripotential stem cells, which are of great importance for clinical application.