Human mesenchymal stem cells make cardiac connexins and form functional gap junctions
Human mesenchymal stem cells make cardiac connexins and form functional gap junctions
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DOI：
10.1113/jphysiol.2003.058719
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发表时间：
2004-03-16
影响因子：
5.5
通讯作者：
Cohen, IS
中科院分区：
文献类型：
--
作者：
Valiunas, V;Doronin, S;Cohen, IS
人间充质干细胞（hMSC）是一种多能细胞群，具有成为细胞修复或递送系统的潜力，前提是它们通过间隙连接与靶细胞（如心肌细胞）通信。免疫染色显示，在hMSCs之间的紧密细胞与细胞接触区域，Cx43和Cx40沿着区域呈典型的点状染色。Cx45的染色模式以颗粒状细胞质染色为代表。hMSCs表现出细胞间偶联彼此，HeLa细胞转染Cx40，Cx43和Cx45和急性分离的犬心室肌细胞。hMSC对之间记录的结电流（I-j）表现出准对称和非对称电压（V-j）依赖性。来自hMSC-HeLaCx 43和hMSC-HeLaCx 40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hMSC-HeLaCx 45细胞对总是产生不对称的I-j，当Cx45侧为负时具有明显的V-j门控。对称I-j表明主要功能通道是同型的，而不对称I-j表明另一种通道类型（异型、异聚体或两者）的活性。hMSC表现出具有30-80 pS的过渡电导（γ（j））的单通道谱。从hMSC-心肌细胞细胞对获得的宏观I-j表现出不对称的V-j依赖性，而单通道事件显示大小范围为40-100 pS的γ（j）。hMSC通过间隙连接与其他细胞类型偶联，为将其视为合胞体（如心肌）的治疗性修复或细胞递送系统提供了基础。
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.