Department of Internal Medicine, Center for Molecular Biotechnology and Center for Research in Experimental Medicine (CeRMS), University of Torino, Torino, Italy.
Curr Opin Nephrol Hypertens. 2010 Jan;19(1):7-12. doi: 10.1097/MNH.0b013e328332fb6f.
The mechanism of stem cell-induced kidney repair remains controversial. Engraftment of bone marrow-derived stem cells is considered a rare event and several studies point to paracrine/endocrine processes. This review focuses on microvesicle-mediated transfer of genetic information between stem cells and injured tissue as a paracrine/endocrine mechanism.
The following findings support a bidirectional exchange of genetic information between stem and injured cells: microvesicles shuttle defined patterns of mRNA and microRNA, are actively released from embryonic and adult stem cells and are internalized by a receptor-mediated mechanism in target cells; transcripts delivered by microvesicles from injured cells may reprogram the phenotype of stem cells to acquire specific features of the tissue; transcripts delivered by microvesicles from stem cells may induce dedifferentiation of cells surviving injury with cell cycle reentry and tissue self-repair.
Transfer of genetic information from injured cells may explain stem cell functional and phenotypic changes without the need for transdifferentiation into tissue cells. On the contrary, transfer of genetic information from stem cells may redirect altered functions in target cells suggesting that stem cells may repair damaged tissues without directly replacing parenchymal cells.
干细胞诱导肾脏修复的机制仍存在争议。骨髓来源的干细胞的植入被认为是一种罕见的事件,有几项研究指出旁分泌/内分泌过程。本综述重点关注干细胞和受损组织之间通过微小囊泡介导的遗传信息转移作为旁分泌/内分泌机制。
以下发现支持干细胞和受损细胞之间遗传信息的双向交换:微小囊泡转运特定模式的 mRNA 和 microRNA,从胚胎和成体干细胞中被主动释放,并通过受体介导的机制被靶细胞内化;来自受损细胞的微小囊泡传递的转录本可能重编程干细胞的表型,使其获得组织的特定特征;来自干细胞的微小囊泡传递的转录本可能诱导损伤后存活的细胞去分化,使细胞周期重新进入并进行组织自我修复。
来自受损细胞的遗传信息的转移可以解释干细胞的功能和表型变化,而不需要向组织细胞分化。相反,来自干细胞的遗传信息的转移可以改变靶细胞的功能,这表明干细胞可以修复受损组织,而不需要直接替代实质细胞。