Multipotent stromal cells from human marrow home to and promote repair of pancreatic islets and renal glomeruli in diabetic NOD/scid mice
Multipotent stromal cells from human marrow home to and promote repair of pancreatic islets and renal glomeruli in diabetic NOD/scid mice
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DOI：
10.1073/pnas.0608249103
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发表时间：
2006-11-14
影响因子：
11.1
通讯作者：
Prockop, Darwin J.
中科院分区：
文献类型：
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作者：
Lee, Ryang Hwa;Seo, Min Jeong;Prockop, Darwin J.
我们验证了来自人骨髓的多能基质细胞（hMSCs）可以为人类糖尿病提供潜在治疗的假设。在NOD/scid小鼠中，在第1-4天每天低剂量的链脲佐菌素产生严重但非致死性的高血糖，并且在第10天和第17天通过心内输注递送hMSCs。相对于未处理的对照，hMSC在第32天降低了糖尿病小鼠中的血糖水平（18.34 mM +/- 1.12 SE对27.78 mM +/- 2.45 SE，P = 0.0019）。ELISA结果表明，与未治疗的糖尿病小鼠相比，hMSC治疗的小鼠血液胰岛素水平较高，但未检测到人胰岛素。PCR分析在第17或32天在胰腺和肾脏的DNA中检测到人Alu序列，但在除心脏以外的其他组织中未检测到人Alu序列，其中细胞被注入。在hMSC治疗的糖尿病小鼠中，胰岛和β细胞产生小鼠胰岛素的增加。罕见的胰岛含有共同标记人胰岛素或PDX-1的人类细胞。胰岛中的大多数β细胞是表达小鼠胰岛素的小鼠细胞。在hMSC处理的糖尿病小鼠的肾脏中，在肾小球中发现人细胞。肾小球系膜增厚减少，巨噬细胞浸润减少。少数人类细胞似乎分化成肾小球内皮细胞。因此，这些结果提出了hMSCs可能有助于增强胰岛素分泌，并可能改善糖尿病患者的肾脏病变的可能性。
We tested the hypothesis that multipotent stromal cells from human bone marrow (hMSCs) can provide a potential therapy for human diabetes mellitus. Severe but nonlethal hyperglycemia was produced in NOD/scid mice with daily low doses of streptozotocin on days 1-4, and hMSCs were delivered via intracardiac infusion on days 10 and 17. The hMSCs lowered blood glucose levels in the diabetic mice on day 32 relative to untreated controls (18.34 mM +/- 1.12 SE vs. 27.78 mM +/- 2.45 SE, P = 0.0019). ELISAs demonstrated that blood levels of mouse insulin were higher in the hMSC-treated as compared with untreated diabetic mice, but human insulin was not detected. PCR assays detected human Alu sequences in DNA in pancreas and kidney on day 17 or 32 but not in other tissues, except heart, into which the cells were infused. In the hMSC-treated diabetic mice, there was an increase in pancreatic islets and beta cells producing mouse insulin. Rare islets contained human cells that colabeled for human insulin or PDX-1. Most of the beta cells in the islets were mouse cells that expressed mouse insulin. in kidneys of hMSC-treated diabetic mice, human cells were found in the glomeruli. There was a decrease in mesangial thickening and a decrease in macrophage infiltration. A few of the human cells appeared to differentiate into glomerular endothelial cells. Therefore, the results raised the possibility that hMSCs may be useful in enhancing insulin secretion and perhaps improving the renal lesions that develop in patients with diabetes mellitus.