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人间充质干细胞产生心脏连接蛋白并形成功能性缝隙连接。

Human mesenchymal stem cells make cardiac connexins and form functional gap junctions.

作者信息

Valiunas Virginijus, Doronin Sergey, Valiuniene Laima, Potapova Irina, Zuckerman Joan, Walcott Benjamin, Robinson Richard B, Rosen Michael R, Brink Peter R, Cohen Ira S

机构信息

Department of Physiology and Biophysics, State University of New York at Stony Brook, Stony Brook, NY 11794-8661, USA.

出版信息

J Physiol. 2004 Mar 16;555(Pt 3):617-26. doi: 10.1113/jphysiol.2003.058719. Epub 2004 Feb 6.

Abstract

Human mesenchymal stem cells (hMSCs) are a multipotent cell population with the potential to be a cellular repair or delivery system provided that they communicate with target cells such as cardiac myocytes via gap junctions. Immunostaining revealed typical punctate staining for Cx43 and Cx40 along regions of intimate cell-to-cell contact between hMSCs. The staining patterns for Cx45 rather were typified by granular cytoplasmic staining. hMSCs exhibited cell-to-cell coupling to each other, to HeLa cells transfected with Cx40, Cx43 and Cx45 and to acutely isolated canine ventricular myocytes. The junctional currents (I(j)) recorded between hMSC pairs exhibited quasi-symmetrical and asymmetrical voltage (V(j)) dependence. I(j) records from hMSC-HeLaCx43 and hMSC-HeLaCx40 cell pairs also showed symmetrical and asymmetrical V(j) dependence, while hMSC-HeLaCx45 pairs always produced asymmetrical I(j) with pronounced V(j) gating when the Cx45 side was negative. Symmetrical I(j) suggests that the dominant functional channel is homotypic, while the asymmetrical I(j) suggests the activity of another channel type (heterotypic, heteromeric or both). The hMSCs exhibited a spectrum of single channels with transition conductances (gamma(j)) of 30-80 pS. The macroscopic I(j) obtained from hMSC-cardiac myocyte cell pairs exhibited asymmetrical V(j) dependence, while single channel events revealed gamma(j) of the size range 40-100 pS. hMSC coupling via gap junctions to other cell types provides the basis for considering them as a therapeutic repair or cellular delivery system to syncytia such as the myocardium.

摘要

人间充质干细胞(hMSCs)是一种多能细胞群体,倘若它们能通过间隙连接与诸如心肌细胞等靶细胞进行通讯,就有可能成为一种细胞修复或递送系统。免疫染色显示,在hMSCs之间紧密的细胞间接触区域,Cx43和Cx40呈现典型的点状染色。Cx45的染色模式则以颗粒状胞质染色为特征。hMSCs彼此之间、与转染了Cx40、Cx43和Cx45的HeLa细胞以及急性分离的犬心室肌细胞之间均表现出细胞间偶联。在hMSC对之间记录到的连接电流(I(j))呈现准对称和不对称电压(V(j))依赖性。来自hMSC-HeLaCx43和hMSC-HeLaCx40细胞对的I(j)记录也显示出对称和不对称的V(j)依赖性,而当Cx45一侧为负时,hMSC-HeLaCx45对总是产生不对称的I(j)且具有明显的V(j)门控。对称的I(j)表明主要的功能通道是同型的,而不对称的I(j)则表明存在另一种通道类型(异型、异聚体或两者皆有)的活性。hMSCs表现出一系列单通道,其过渡电导(gamma(j))为30 - 80 pS。从hMSC - 心肌细胞对获得的宏观I(j)呈现不对称的V(j)依赖性,而单通道事件显示gamma(j)在40 - 100 pS的大小范围内。hMSCs通过间隙连接与其他细胞类型的偶联为将它们视为向诸如心肌等合体细胞的治疗性修复或细胞递送系统提供了基础。

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