Mesenchymal stroma cells improve hyperglycemia and insulin deficiency in the diabetic porcine pancreatic microenvironment
Mesenchymal stroma cells improve hyperglycemia and insulin deficiency in the diabetic porcine pancreatic microenvironment
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DOI：
10.1080/14653240802461924
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发表时间：
2008-01-01
期刊：
影响因子：
4.5
通讯作者：
Gong, F.
中科院分区：
文献类型：
--
作者：
Chang, C.;Niu, D.;Gong, F.
背景干细胞分化是由来自环境的细胞外信号和干细胞内的内在遗传程序控制的。本研究旨在探讨间充质基质细胞（MSC）是否能够改善糖尿病微环境中的高血糖和胰岛素产生。方法通过多点注射将雄性猪骨髓来源的表达EGFP的MSC直接移植到雌性糖尿病猪胰腺中。采用酶联免疫吸附测定（ELISA）和荧光免疫组织化学分析受者血清和胰腺组织，以评估治疗效果。结果与未治疗的糖尿病对照相比，MSC治疗的受者从移植后15天开始血糖水平逐渐下降（15.94+/-0.31mmol/L） 对比 16.66 +/- 0.11 mmol/L； P = 0.01）。与未治疗的糖尿病对照相比，移植后两周后受者的血液胰岛素显着增加，胰高血糖素显着下降（0.049+/-0.004μg/L与0.037+/-0.02μg/L以及392.9+/-20.3ng/L与433.1+/-27.6ng/L）。苏木精和伊红 (HE) 染色切片表明，与糖尿病对照相比，受者每个切片的胰岛数量显着增加（10.9 +/- 2.2 与 4.6 +/- 1.4；P < 0.05），并且与正常对照相似（10.9 +/- 2.2 与 12.6 +/- 2.6；P > 0.05）。新形成的胰岛比正常胰岛小（47.2+/-19.6μm vs 119.6+/-27.7μm；P<0.05）。对受者胰腺切片的 EGFP 分析表明，移植的 MSC 在胰腺内存活。胰岛的胰岛素免疫反应表明新形成的胰岛表达胰岛素。讨论：MSC可以改善糖尿病患者的胰腺微环境，且无明显的免疫排斥反应。这具有理论和临床应用。
BackgroundStem cell differentiation is controlled by extracellular cues from the environment and by intrinsic genetic programs within the stem cell. The present study aimed to explore whether mesenchymal stromal cells (MSC) could improve hyperglycemia and insulin production in the diabetic microenvironment.MethodsWe transplanted male porcine bone marrow-derived EGFP-expressing MSC directly into female diabetic porcine pancreas by multi-point injection. Enzyme-linked immunosorbent assay (ELISA) and fluorescent immunohistochemistry were used to analyze recipients' sera and pancreas tissues for assessment of the therapeutic effect.ResultsBlood glucose levels decreased gradually in MSC-treated recipients from 15 days after the transplantation compared with untreated diabetic controls (15.94 +/- 0.31 mmol/L versus 16.66 +/- 0.11 mmol/L; P = 0.01). Blood insulin increased and glucagons decreased notably in recipients from 2 weeks post-transplantation compared with untreated diabetic controls (0.049 +/- 0.004 mu g/L versus 0.037 +/- 0.02 mu g/L and 392.9 +/- 20.3 ng/L versus 433.1 +/- 27.6 ng/L). Hematoxylin and eosin (HE)-stained sections demonstrated that the number of islets from each section was markedly increased in recipients compared with that of diabetic controls (10.9 +/- 2.2 versus 4.6 +/- 1.4; P < 0.05) and similar to that of normal controls (10.9 +/- 2.2 versus 12.6 +/- 2.6; P > 0.05). The newly formed islets were smaller than normal islets (47.2 +/- 19.6 mu m versus 119.6 +/- 27.7 mu m; P < 0.05). Analysis of pancreatic sections for EGFP in recipients indicated that the transplanted MSC survived within the pancreas. Insulin immunoreactivity of pancreatic islets showed that the newly formed islets expressed insulin.Discussion:MSC could improve diabetes upon pancreatic microenvironment without obvious immune rejections. This has theoretical and clinical applications.