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用人间充质干细胞在子宫内移植的绵羊中持续循环的人胰岛素。

Persistent circulating human insulin in sheep transplanted in utero with human mesenchymal stem cells.

机构信息

Department of Animal Biotechnology, University of Nevada Reno, Reno, NV, USA.

出版信息

Exp Hematol. 2010 Apr;38(4):311-20. doi: 10.1016/j.exphem.2010.02.005. Epub 2010 Feb 17.

Abstract

OBJECTIVE

To determine if mesenchymal stem cells (MSC) derived from human fetal pancreatic tissue (pMSC) would engraft and differentiate in sheep pancreas following transplantation in utero.

MATERIALS AND METHODS

A three-step culture system was established for generating human fetal pMSC. Sheep fetuses were transplanted during the fetal transplant receptivity period with human pMSC and evaluated for in situ and functional engraftment in their pancreas, liver, and bone marrow.

RESULTS

Isolation and expansion of adherent cells from the human fetal pancreas yielded a cell population with morphologic and phenotypic characteristics similar to MSC derived from bone marrow. This putative stem cell population could undergo multilineage differentiation in vitro. Three to 27 months after fetal transplantation, the pancreatic engraftment frequency (chimeric index) was 79%, while functional engraftment was noted in 50% of transplanted sheep. Hepatic and marrow engraftment and expression was noted as well.

CONCLUSION

We have established a procedure for isolation of human fetal pMSC that display characteristics similar to bone marrow-derived MSC. In vivo results suggest the pMSC engraft, differentiate, and secrete human insulin from the sheep pancreas.

摘要

目的

确定源自人胎儿胰腺组织(pMSC)的间充质干细胞(MSC)是否会在宫内移植后在绵羊胰腺中定植和分化。

材料和方法

建立了一个三步培养系统来生成人胎儿 pMSC。在胎儿接受移植期,将绵羊胎儿与人类 pMSC 一起移植,并评估其在胰腺、肝脏和骨髓中的原位和功能定植情况。

结果

从人胎儿胰腺中分离和扩增贴壁细胞产生了一种具有类似于骨髓来源 MSC 的形态和表型特征的细胞群体。这种假定的干细胞群体可以在体外进行多谱系分化。在胎儿移植后 3 至 27 个月时,胰腺定植频率(嵌合指数)为 79%,而在 50%的移植绵羊中观察到功能性定植。也观察到肝和骨髓的定植和表达。

结论

我们已经建立了一种分离人胎儿 pMSC 的方法,其显示出与骨髓来源 MSC 相似的特征。体内结果表明 pMSC 定植、分化,并从绵羊胰腺中分泌人胰岛素。

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