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经5-氮杂胞苷处理的源自脐带、脐血和骨髓的人间充质干/祖细胞在体外并不能高频产生心肌细胞。

5-Azacytidine-treated human mesenchymal stem/progenitor cells derived from umbilical cord, cord blood and bone marrow do not generate cardiomyocytes in vitro at high frequencies.

作者信息

Martin-Rendon E, Sweeney D, Lu F, Girdlestone J, Navarrete C, Watt S M

机构信息

Stem Cell Research Laboratory, NHS-Blood and Transplant, John Radcliffe Hospital, Headington, Oxford, UK.

出版信息

Vox Sang. 2008 Aug;95(2):137-48. doi: 10.1111/j.1423-0410.2008.01076.x. Epub 2008 Jun 28.

DOI:10.1111/j.1423-0410.2008.01076.x
PMID:18557828
Abstract

BACKGROUND AND OBJECTIVES

Mesenchymal stem/progenitor cells (MSCs) are multipotent progenitors that differentiate into such lineages as bone, fat, cartilage and stromal cells that support haemopoiesis. Bone marrow MSCs can also contribute to cardiac repair, although the mechanism for this is unclear. Here, we examine the potential of MSCs from different sources to generate cardiomyocytes in vitro, as a means for predicting their therapeutic potential after myocardial infarction.

MATERIALS AND METHODS

Mesenchymal stem/progenitor cells were isolated from the perivascular tissue and Wharton's jelly of the umbilical cord and from cord blood. Their immunophenotype and differentiation potential to generate osteoblasts, chondrocytes, adipocytes and cardiomyoxcytes in vitro was compared with those of bone marrow MSCs.

RESULTS

Mesenchymal stem/progenitor cells isolated from umbilical cord and cord blood were phenotypically similar to bone marrow MSCs, the exception being in the expression of CD106, which was absent on umbilical cord MSCs, and CD146 that was highly expressed in cord blood MSCs. They have variable abilities to give rise to osteoblasts, chondrocytes and adipocytes, with bone marrow MSCs being the most robust. While a small proportion (approximately 0.07%) of bone marrow MSCs could generate cardiomyocyte-like cells in vitro, those from umbilical cord and cord blood did not express cardiac markers either spontaneously or after treatment with 5-azacytidine.

CONCLUSION

Although MSCs may be useful for such clinical applications as bone or cartilage repair, the results presented here indicate that such cells do not generate cardiomyocytes frequently enough for cardiac repair. Their efficacy in heart repair is likely to be due to paracrine mechanisms.

摘要

背景与目的

间充质干/祖细胞(MSCs)是多能祖细胞,可分化为骨、脂肪、软骨和支持造血的基质细胞等谱系。骨髓间充质干细胞也有助于心脏修复,但其机制尚不清楚。在此,我们研究不同来源的间充质干细胞在体外生成心肌细胞的潜力,作为预测其在心肌梗死后治疗潜力的一种方法。

材料与方法

从血管周围组织、脐带华通氏胶和脐带血中分离间充质干/祖细胞。将其免疫表型以及在体外生成成骨细胞、软骨细胞、脂肪细胞和心肌细胞的分化潜力与骨髓间充质干细胞进行比较。

结果

从脐带和脐带血中分离的间充质干/祖细胞在表型上与骨髓间充质干细胞相似,但脐带间充质干细胞不表达CD106,脐带血间充质干细胞高表达CD146。它们生成成骨细胞、软骨细胞和脂肪细胞的能力各不相同,其中骨髓间充质干细胞的能力最强。虽然一小部分(约0.07%)骨髓间充质干细胞可在体外生成心肌样细胞,但脐带和脐带血来源的间充质干细胞无论是自发还是经5-氮杂胞苷处理后均不表达心脏标志物。

结论

尽管间充质干细胞可能对骨或软骨修复等临床应用有用,但本文结果表明,此类细胞生成心肌细胞的频率不足以用于心脏修复。它们在心脏修复中的疗效可能归因于旁分泌机制。

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