Both bone marrow-derived hematopoietic stem cells (HSC) and mesenchymal stem cells (MSC) improve glycemic control in diabetic mice, but their kinetics and associated changes in pancreatic morphology have not been directly compared. Our goal was to examine the time course of improvements in glucose tolerance and associated changes in β-cell mass and proliferation following transplantation of equivalent numbers of HSC or MSC from the same bone marrow into diabetic non-obese diabetic severe combined immune deficiency (NOD.SCID) mice. We used transgenic mice with a targeted expression of yellow fluorescent protein (YFP) driven by the Vav1 gene promoter to genetically tag HSC and progeny. HSC were separated from bone marrow by fluorescence-activated cell sorting and MSC following cell culture. Equivalent numbers of isolated HSC or MSC were transplanted directly into the pancreas of NOD.SCID mice previously made diabetic with streptozotocin. Glucose tolerance, serum insulin, β-cell mass and β-cell proliferation were examined up to 28 days following transplant. Transplantation with MSC improved glucose tolerance within 7 days and serum insulin levels increased, but with no increase in β-cell mass. Mice transplanted with HSC showed improved glucose tolerance only after 3 weeks associated with increased β-cell proliferation and mass. We conclude that single injections of either MSC or HSC transiently improved glycemic control in diabetic NOD.SCID mice, but with different time courses. However, only HSC infiltrated the islets and were associated with an expanded β-cell mass. This suggests that MSC and HSC have differing mechanisms of action.

骨髓来源的造血干细胞（HSC）和间充质干细胞（MSC）均可改善糖尿病小鼠的血糖控制，但尚未对其动力学和相关的胰腺形态变化进行直接比较。我们的目标是研究在同等数量的HSC或MSC从同一骨髓移植到糖尿病非肥胖型糖尿病严重合并免疫缺陷症（NOD）后，改善葡萄糖耐量以及相关的β细胞质量和增殖变化的时程。 SCID）小鼠。我们使用了由Vav1驱动的靶向表达黄色荧光蛋白（YFP）的转基因小鼠基因启动子以遗传标记HSC和后代。细胞培养后，通过荧光激活细胞分选和MSC将HSC与骨髓分离。将等量的分离的HSC或MSC直接移植到NOD的胰腺中。先前用链脲佐菌素制成糖尿病的SCID小鼠。移植后长达28天检查葡萄糖耐量，血清胰岛素，β细胞质量和β细胞增殖。MSC移植可在7天内改善葡萄糖耐量，并且血清胰岛素水平增加，但β细胞质量没有增加。移植了HSC的小鼠仅在3周后表现出改善的葡萄糖耐量，这与增加的β细胞增殖和质量有关。我们得出的结论是，单次注射MSC或HSC可以暂时改善糖尿病NOD.SCID小鼠的血糖控制，但时程不同。但是，只有HSC浸润了胰岛，并与扩大的β细胞团有关。这表明MSC和HSC具有不同的作用机制。