...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>PLoS One >Intrapancreatic injection of human bone marrow-derived mesenchymal stem/stromal cells alleviates hyperglycemia and modulates the macrophage state in streptozotocin-induced type 1 diabetic mice
【24h】

Intrapancreatic injection of human bone marrow-derived mesenchymal stem/stromal cells alleviates hyperglycemia and modulates the macrophage state in streptozotocin-induced type 1 diabetic mice

机译：胰腺内注射人骨髓间充质干/基质细胞可缓解高血糖症，并调节链脲佐菌素诱导的1型糖尿病小鼠的巨噬细胞状态

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Type 1 diabetes mellitus is a progressive disease caused by the destruction of pancreatic β-cells, resulting in insulin dependency and hyperglycemia. While transplanted bone marrow-derived mesenchymal stem/stromal cells (BMMSCs) have been explored as an alternative therapeutic approach for diseases, the choice of delivery route may be a critical factor determining their sustainability. This study evaluated the effects of intrapancreatic and intravenous injection of human BMMSCs (hBMMSCs) in streptozotocin (STZ)-induced type 1 diabetic mouse model. C57/BL6 mice were intraperitoneally injected with 115 mg/kg STZ on day 0. hBMMSCs (1 × 106 cells) or vehicle were injected into the pancreas or jugular vein on day 7. Intrapancreatic, but not intravenous, hBMMSC injection significantly reduced blood glucose levels on day 28 compared with vehicle injection by the same route. This glucose-lowering effect was not induced by intrapancreatic injection of human fibroblasts as the xenograft control. Intrapancreatically injected fluorescence-labeled hBMMSCs were observed in the intra- and extra-lobular spaces of the pancreas, and intravenously injected cells were in the lung region, although the number of cells mostly decreased within 2 weeks of injection. For hBMMSCs injected twice into the pancreatic region on days 7 and 28, the injected mice had further reduced blood glucose to borderline diabetic levels on day 56. Animals injected with hBMMSCs twice exhibited increases in the plasma insulin level, number and size of islets, insulin-positive proportion of the total pancreas area, and intensity of insulin staining compared with vehicle-injected animals. We found a decrease of Iba1-positive cells in islets and an increase of CD206-positive cells in both the endocrine and exocrine pancreas. The hBMMSC injection also reduced the number of CD40-positive cells merged with glucagon immunoreactions in the islets. These results suggest that intrapancreatic injection may be a better delivery route of hBMMSCs for the treatment of type 1 diabetes mellitus.
机译：1型糖尿病是由胰腺β细胞破坏引起的进行性疾病，导致胰岛素依赖和高血糖症。尽管已经探索了移植的骨髓间充质干/基质细胞（BMMSC）作为疾病的替代治疗方法，但选择递送途径可能是决定其可持续性的关键因素。这项研究评估了链脲佐菌素（STZ）诱导的1型糖尿病小鼠模型中胰腺内和静脉内注射人BMMSC（hBMMSC）的影响。在第0天，向C57 / BL6小鼠腹膜内注射115 mg / kg STZ。在第7天，将hBMMSC（1×106细胞）或媒介物注入胰腺或颈静脉。第28天的水平与同路线的车辆注入相比。胰内注射人成纤维细胞作为异种移植对照，未引起这种降低葡萄糖的作用。在胰腺的小叶内和小叶外空间观察到了胰内注射的荧光标记的hBMMSC，而静脉内注射的细胞位于肺区域，尽管在注射后2周内细胞数量大多减少了。对于在第7天和第28天两次注射到胰腺区域的hBMMSC，在第56天注射的小鼠的血糖进一步降低至临界糖尿病水平。两次注射hBMMSC的动物血浆胰岛素水平，胰岛的数量和大小，胰岛素均增加胰总注射面积的阳性比例和与载体注射动物相比的胰岛素染色强度。我们发现胰岛中的Iba1阳性细胞减少，而内分泌和外分泌胰腺中CD206阳性细胞增加。 hBMMSC注射还减少了胰岛中胰高血糖素免疫反应合并的CD40阳性细胞的数量。这些结果表明，胰腺内注射可能是用于治疗1型糖尿病的hBMMSC更好的递送途径。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号