Huss R, von Lüttichau I, Lechner S, Notohamiprodjo M, Seliger C, Nelson P
Pathologisches Institut der Universität München.
Verh Dtsch Ges Pathol. 2004;88:170-3.
A major challenge in stem cell biology is to study the underlying mechanisms of tissue specific homing and differentiation. Recent results suggest that bone marrow derived stem cells can give rise to multiple cell types. Because chemokines and chemokine receptors are associated with development, differentiation and homing of immune cells, we undertook efforts to study the chemokine receptor expression profile of human adult stem cells to identify their potential role in tissue specific homing prior to transdifferentiation. Using human bone marrow-derived stem cell lines, we could demonstrate functional chemokine receptor expression of various chemokine receptors. The expression of CXCR5 and CCR7, associated with secondary lymphoid organ homing as well as CXCR4 and CCR10, involved in organ specific homing and CXCR3, CCR5 and CCR1, which are involved in inflammation events, suggested a role of chemokine receptors in tissue specific homing of stem cells. To proof the specific homing of stem cells in vivo, we used murine stem cell lines, stably introduced green fluorescent protein under control of CMV promotor into the cells and injected them intravenously into mice. We demonstrate the homing of these stem cells to lymphnode and thymus as well as mucosal tissue, while stem cells home exclusively to a site of lesion during wound healing and tissue regeneration. Our data suggest that chemokine biology may play a pivotal role in the homing of stem cells to specific tissues and niches prior to (trans)differentiation, while the homing changes during tissue damage and other adequate lesions.
干细胞生物学中的一个主要挑战是研究组织特异性归巢和分化的潜在机制。最近的研究结果表明,骨髓来源的干细胞可以分化为多种细胞类型。由于趋化因子和趋化因子受体与免疫细胞的发育、分化和归巢相关,我们致力于研究人类成体干细胞的趋化因子受体表达谱,以确定它们在转分化之前在组织特异性归巢中的潜在作用。利用人类骨髓来源的干细胞系,我们能够证明各种趋化因子受体的功能性表达。与次级淋巴器官归巢相关的CXCR5和CCR7以及参与器官特异性归巢的CXCR4和CCR10,还有参与炎症反应的CXCR3、CCR5和CCR1的表达,表明趋化因子受体在干细胞的组织特异性归巢中发挥作用。为了在体内验证干细胞的特异性归巢,我们使用了小鼠干细胞系,在CMV启动子的控制下将绿色荧光蛋白稳定导入细胞,并将其静脉注射到小鼠体内。我们证明了这些干细胞归巢到淋巴结、胸腺以及黏膜组织,而在伤口愈合和组织再生过程中,干细胞仅归巢到损伤部位。我们的数据表明,趋化因子生物学可能在干细胞(转)分化之前归巢到特定组织和微环境中发挥关键作用,而在组织损伤和其他适当损伤过程中归巢情况会发生变化。