Engrafted bone marrow-derived Flk-1+ mesenchymal stem cells regenerate skin tissue
Engrafted bone marrow-derived Flk-1+ mesenchymal stem cells regenerate skin tissue
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DOI：
10.1089/ten.2005.11.110
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发表时间：
2005-01-01
影响因子：
--
通讯作者：
Zhao, RCH
中科院分区：
文献类型：
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作者：
Deng, WM;Han, Q;Zhao, RCH
干细胞可塑性在退行性或遗传性疾病中具有潜在的治疗应用价值，引起了人们极大的兴趣。骨髓源性干细胞移植后可分化为肌肉、肝脏、神经、内皮、上皮等细胞，但关于干细胞的可塑性，特别是骨髓源性干细胞对皮肤细胞的贡献，目前仍存在争议。在本研究中，将CM-DiI荧光标记的BALB/c小鼠（H-2K（d），白色）的Flk-1（+）骨髓间充质干细胞（bMSCs）移植到致死辐射的C57 BL/6小鼠（H-2K（B），黑色）中。通过荧光示踪发现供者细胞可以迁移并在皮肤上定居，这一结果得到了Y染色体特异性PCR和Southern blot的证实。约40天后，受体小鼠长出白色毛发，并且白色毛发可以遍布全身。免疫组化染色和RT-PCR结果显示，白色毛发区域的皮肤组织主要由供者来源的H-2K（d）细胞组成，包括干细胞和定向细胞。此外，从白色毛发皮肤培养的大多数皮肤细胞来源于供体。因此，我们的研究结果提供了直接证据，证明骨髓来源的细胞可以产生功能性皮肤细胞并再生皮肤组织。这些可能在干细胞生物学和皮肤组织损伤的移植治疗中具有重要的科学意义。
Stem cell plasticity has created great interest because of its potential therapeutic application in degenerative or inherited diseases. Transplantation of bone marrow-derived stem cells was shown to give rise to cells of muscle, liver, nerve, endothelium, epithelium, and so on. But there are still disputes about stem cell plasticity, especially concerning the contribution of bone marrow-derived cells to skin cells. In this study, CM-DiI fluorescence-labeled Flk-1(+) bone marrow mesenchymal stem cells (bMSCs) of BALB/c mice (H-2K(d), white) were transplanted into lethally irradiated C57BL/6 mice ( H-2K(b), black). By fluorescence tracing, we found that donor cells could migrate and take residency at the skin, which was confirmed by Y chromosome-specific PCR and Southern blot. The recipient mice grew white hairs about 40 days later and white hairs could spread over the body. Immunochemistry staining and RT-PCR demonstrated that skin tissue within the white hair regions was largely composed of donor-derived H-2K(d) cells, including stem cells and committed cells. Furthermore, most skin cells cultured from white hair skin originated from the donor. Thus, our findings provide direct evidence that bone marrow-derived cells can give rise to functional skin cells and regenerate skin tissue. These may have important scientific implications in stem cell biology and transplantation therapy for skin tissue injury.