Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells into Insulin-Producing Cells: Evidence for Further Maturation In Vivo.
Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells into Insulin-Producing Cells: Evidence for Further Maturation In Vivo.
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DOI：
10.1155/2015/575837
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发表时间：
2015
影响因子：
--
通讯作者：
Ghoneim MA
中科院分区：
文献类型：
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作者：
Gabr MM;Zakaria MM;Refaie AF;Khater SM;Ashamallah SA;Ismail AM;El-Halawani SM;Ghoneim MA
本研究旨在为人骨髓间充质干细胞（HBM-MSCs）体外诱导胰岛素分泌细胞（IPC）的进一步成熟提供实验依据。从三名胰岛素依赖型2型糖尿病志愿者获得HBM-MSC。扩增后，根据阿司他汀-A/GLP方案使细胞分化。将100万个细胞移植到29只糖尿病裸鼠的肾包膜下。测定血糖、血清人胰岛素和c肽水平以及葡萄糖耐量曲线。移植后1、2、4或12周对小鼠实施安乐死。对携带IPC的肾脏进行免疫标记，计数IPC的数量，并测定相关基因的表达。在体外分化结束时，所有胰腺内分泌基因表达，尽管在非常低的值。IPC在移植细胞中所占的百分比很小（≤3%）。糖尿病动物在移植后8 ± 3天血糖正常。此后，IPC的百分比在4周时达到平均约18%。胰岛素、胰高血糖素和生长抑素的相对基因表达呈平行增加。移植细胞诱导真核表达的能力是由于它们在有利的体内微环境中进一步成熟。所涉及的确切机制需要进一步研究。
The aim of this study was to provide evidence for further in vivo maturation of insulin-producing cells (IPCs) derived from human bone marrow-derived mesenchymal stem cells (HBM-MSCs). HBM-MSCs were obtained from three insulin-dependent type 2 diabetic volunteers. Following expansion, cells were differentiated according to a trichostatin-A/GLP protocol. One million cells were transplanted under the renal capsule of 29 diabetic nude mice. Blood glucose, serum human insulin and c-peptide levels, and glucose tolerance curves were determined. Mice were euthanized 1, 2, 4, or 12 weeks after transplantation. IPC-bearing kidneys were immunolabeled, number of IPCs was counted, and expression of relevant genes was determined. At the end of in vitro differentiation, all pancreatic endocrine genes were expressed, albeit at very low values. The percentage of IPCs among transplanted cells was small (≤3%). Diabetic animals became euglycemic 8 ± 3 days after transplantation. Thereafter, the percentage of IPCs reached a mean of ~18% at 4 weeks. Relative gene expression of insulin, glucagon, and somatostatin showed a parallel increase. The ability of the transplanted cells to induce euglycemia was due to their further maturation in the favorable in vivo microenvironment. Elucidation of the exact mechanism(s) involved requires further investigation.
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影响因子：
5.2
作者：
Moriscot, C;De Fraipont, F;Benhamou, PY
通讯作者：
Benhamou, PY
影响因子：
46.9
作者：
Kroon, Evert;Martinson, Laura A.;Baetge, Emmanuel E.
通讯作者：
Baetge, Emmanuel E.
DOI：
10.1073/pnas.0911647107
发表时间：
2010-05-11
影响因子：
11.1
作者：
Kuroda, Yasumasa;Kitada, Masaaki;Dezawa, Mari
通讯作者：
Dezawa, Mari
影响因子：
2.8
作者：
CAPLAN, AI
通讯作者：
CAPLAN, AI
DOI：
10.1038/nrm3049
发表时间：
2011-02
期刊：
Nature reviews. Molecular cell biology
影响因子：
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作者：
通讯作者：
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