Luo LuGuang, Luo John Z Q, Xiong Fang, Abedi Mehrdad, Greer Deborah
Center for Stem Cell Biology, Roger Williams Hospital, Providence, Rhode Island, United States of America.
PLoS One. 2009;4(2):e4504. doi: 10.1371/journal.pone.0004504. Epub 2009 Feb 19.
We hypothesize that specific bone marrow lineages and cytokine treatment may facilitate bone marrow migration into islets, leading to a conversion into insulin producing cells in vivo. In this study we focused on identifying which bone marrow subpopulations and cytokine treatments play a role in bone marrow supporting islet function in vivo by evaluating whether bone marrow is capable of migrating into islets as well as converting into insulin positive cells. We approached this aim by utilizing several bone marrow lineages and cytokine-treated bone marrow from green fluorescent protein (GFP) positive bone marrow donors. Sorted lineages of Mac-1(+), Mac-1(-), Sca(+), Sca(-), Sca(-)/Mac-1(+) and Sca(+)/Mac-1(-) from GFP positive mice were transplanted to irradiated C57BL6 GFP negative mice. Bone marrow from transgenic human ubiquitin C promoter GFP (uGFP, with strong signal) C57BL6 mice was transplanted into GFP negative C57BL6 recipients. After eight weeks, migration of GFP positive donor' bone marrow to the recipient's pancreatic islets was evaluated as the percentage of positive GFP islets/total islets. The results show that the most effective migration comes from the Sca(+)/Mac(-) lineage and these cells, treated with cytokines for 48 hours, were found to have converted into insulin positive cells in pancreatic islets in vivo. This study suggests that bone marrow lineage positive cells and cytokine treatments are critical factors in determining whether bone marrow is able to migrate and form insulin producing cells in vivo. The mechanisms causing this facilitation as well as bone marrow converting to pancreatic beta cells still need to be investigated.
我们推测特定的骨髓谱系和细胞因子处理可能会促进骨髓迁移至胰岛，从而在体内转化为胰岛素生成细胞。在本研究中，我们聚焦于通过评估骨髓是否能够迁移至胰岛以及是否能转化为胰岛素阳性细胞，来确定哪些骨髓亚群和细胞因子处理在体内支持胰岛功能中发挥作用。我们通过利用来自绿色荧光蛋白（GFP）阳性骨髓供体的几种骨髓谱系和经细胞因子处理的骨髓来实现这一目标。将来自GFP阳性小鼠的Mac-1(+)、Mac-1(-)、Sca(+)、Sca(-)、Sca(-)/Mac-1(+)和Sca(+)/Mac-1(-)分选谱系移植到经照射的C57BL6 GFP阴性小鼠体内。将来自转基因人泛素C启动子GFP（uGFP，信号强）C57BL6小鼠的骨髓移植到GFP阴性的C57BL6受体小鼠体内。八周后，将GFP阳性供体骨髓向受体胰腺胰岛的迁移情况评估为GFP阳性胰岛占总胰岛的百分比。结果显示，最有效的迁移来自Sca(+)/Mac(-)谱系，并且发现这些经细胞因子处理48小时的细胞在体内胰腺胰岛中已转化为胰岛素阳性细胞。本研究表明，骨髓谱系阳性细胞和细胞因子处理是决定骨髓在体内是否能够迁移并形成胰岛素生成细胞的关键因素。导致这种促进作用以及骨髓转化为胰腺β细胞的机制仍有待研究。
