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

Persistent circulating human insulin in sheep transplanted in utero with human mesenchymal stem cells
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DOI:
10.1016/j.exphem.2010.02.005
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发表时间:
2010-04-01
影响因子:
2.6
通讯作者:
Zanjani, Esmail D.
Zanjani, Esmail D.
中科院分区:
医学4区
文献类型:
--
作者:
Ersek, Adel;Pixley, John S.;Zanjani, Esmail D.

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Objective.目的:探讨人胚胎胰腺组织(pMSC)来源的间充质干细胞(MSC)在子宫内移植后能否在绵羊胰腺内移植并分化。建立了人胎儿骨髓间充质干细胞的三步培养体系。在胚胎移植受体期将人pMSC移植到绵羊胚胎中,并评估其胰腺、肝脏和骨髓中的原位和功能性植入。从人胎儿胰腺中分离和扩增贴壁细胞产生了一个细胞群,其形态和表型特征类似于骨髓来源的MSC。这种假定的干细胞群体可以在体外经历多谱系分化。胚胎移植后3 - 27个月,胰腺植入频率(嵌合指数)为79%,而在50%的移植绵羊中观察到功能性植入。肝脏和骨髓移植和表达。我们已经建立了一种分离人胎儿pMSC的方法,该方法显示出与骨髓来源的MSC相似的特征。体内结果表明,pMSC植入,分化,并分泌人胰岛素从羊胰腺。爱思唯尔公司出版代表血液学和干细胞学会(C)2010 ISEH -血液学和干细胞学会。爱思唯尔公司出版
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. Published by Elsevier Inc. on behalf of the Society for Hematology and Stem Cells (C) 2010 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.