In vitro cardiomyogenic potential of human amniotic fluid stem cells.

In vitro cardiomyogenic potential of human amniotic fluid stem cells.
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DOI:
10.1002/term.308
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发表时间:
2011-03
影响因子:
3.3
通讯作者:
Soker, Shay
Soker, Shay
中科院分区:
工程技术3区
文献类型:
--
作者:
Guan, Xuan;Delo, Dawn M.;Atala, Anthony;Soker, Shay

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干细胞治疗受损心脏组织目前受到许多因素的限制,包括无法获得足够的细胞数量,某些类型的干细胞的潜在致瘤性,以及干细胞治疗与恶性心律失常的发展之间可能存在的联系。在这项研究中,我们通过测试体外分化能力来研究人类羊水来源干细胞(hAFS)是否可能成为心脏细胞治疗的潜在细胞来源。未分化的hAFS细胞表达多种心脏基因,包括转录因子mef2、间隙连接蛋白connexin43以及H-和n -钙粘蛋白。5-aza-2 ' -脱氧胞苷(5-AZA-dC) 24小时孵育诱导hAFS细胞沿心脏谱系分化。这种分化的证据包括形态学改变、心脏特异性基因(心肌肌钙蛋白I和心肌肌钙蛋白T)的上调和connexin43的重新分布,以及干细胞标记物SRY-box 2 (sox2)的下调。当与新生大鼠心肌细胞(NRCs)共培养时,hAFS细胞与NRCs形成了机械和电连接。染料转移实验表明,钙黄蛋白染料可以通过细胞连接从NRCs转移到hAFS细胞。由于12-O-Tetradecanoylphorbol 13-acetate (TPA)可以部分阻断细胞串扰,因此间隙连接蛋白43可能参与了两种细胞类型之间的通信。我们得出结论,hAFS细胞可以分化为心肌细胞样表型,并可以与NRCs建立功能通信。因此,hAFS细胞有可能用于心脏细胞治疗。
Stem cell therapy for damaged cardiac tissue is currently limited by a number of factors, including the inability to obtain sufficient cell numbers, the potential tumorigenicity of certain types of stem cells, and the possible link between stem cell therapy and the development of malignant arrhythmias. In this study, we investigated whether human amniotic fluid-derived stem (hAFS) cells could be a potential source of cells for cardiac cell therapy by testing the in vitro differentiation capabilities. Undifferentiated hAFS cells express several cardiac genes, including the transcription factor mef2, the gap junction connexin43, and H- and N-cadherin. A 24-hour incubation with 5-aza-2′–deoxycytidine (5-AZA-dC) induced hAFS cell differentiation along the cardiac lineage. Evidence for this differentiation included morphological changes, up-regulation of cardiac-specific genes (cardiac troponin I and cardiac troponin T) and redistribution of connexin43, as well as down-regulation of the stem cell marker SRY-box 2 (sox2). When co-cultured with neonatal rat cardiomyocytes (NRCs), hAFS cells formed both mechanical and electrical connections with the NRCs. Dye transfer experiments showed that calcein dye could be transferred from NRCs to hAFS cells through cellular connections. The gap junction connexin 43 likely involved in the communication between the two cell types, because 12-O-Tetradecanoylphorbol 13-acetate (TPA) could partially block cellular crosstalk. We conclude that hAFS cells can be differentiated into a cardiomyocyte-like phenotype and can establish functional communication with NRCs. Thus, hAFS cells may potentially be used for cardiac cell therapy.
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