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鉴定在心室肌细胞死亡后存在于缺血人心肌中的心脏祖细胞。

Identification of cardiac progenitors that survive in the ischemic human heart after ventricular myocyte death.

机构信息

Department of Physiology, Shiga University of Medical Science, Otsu, Shiga, 520-2192, Japan.

Department of Pathology, Shiga University of Medical Science, Otsu, Shiga, 520-2192, Japan.

出版信息

Sci Rep. 2017 Jan 25;7:41318. doi: 10.1038/srep41318.

Abstract

Atypically-shaped cardiomyocytes (ACMs) are beating heart cells identified in the cultures of cardiomyocyte-removed fractions obtained from adult mouse hearts. Since ACMs spontaneously develop into beating cells in the absence of hormones or chemicals, these cells are likely to be a type of cardiac progenitors rather than stem cells. "Native ACMs" are found as small interstitial cells among ventricular myocytes that co-express cellular prion protein (PrP) and cardiac troponin T (cTnT) in mouse and human heart tissues. However, the endogenous behavior of human ACMs is unclear. In the present study, we demonstrate that PrP cTnT cells are present in the human heart tissue with myocardial infarction (MI). These cells were mainly found in the border of necrotic cardiomyocytes caused by infarcts and also in the hibernating myocardium subjected to the chronic ischemia. The ratio of PrP cTnT cells to the total cells observed in the normal heart tissue section of mouse and human was estimated to range from 0.3-0.8%. Notably, living human PrP cTnT cells were identified in the cultures obtained at pathological autopsy despite exposure to lethal ischemic conditions for hours after death. These findings suggest that ACMs could survive in the ischemic human heart and develop into a sub-population of cardiac myocytes.

摘要

非典型形态心肌细胞(ACMs)是在从成年小鼠心脏中去除心肌细胞的培养物中鉴定出的搏动心脏细胞。由于 ACMs 在没有激素或化学物质的情况下自发发育为搏动细胞,因此这些细胞可能是一种心脏祖细胞,而不是干细胞。“天然 ACMs”作为小的间质细胞存在于心室肌细胞之间,在小鼠和人心脏组织中共同表达细胞朊病毒蛋白(PrP)和心肌肌钙蛋白 T(cTnT)。然而,人 ACMs 的内源性行为尚不清楚。在本研究中,我们证明了 PrP cTnT 细胞存在于心肌梗死(MI)的人类心脏组织中。这些细胞主要存在于梗死引起的坏死心肌细胞的边界处,也存在于慢性缺血引起的冬眠心肌中。在小鼠和人正常心脏组织切片中观察到的 PrP cTnT 细胞与总细胞的比例估计在 0.3-0.8%之间。值得注意的是,尽管在死亡后数小时内暴露于致命的缺血条件下,仍在尸检时获得的培养物中鉴定出存活的人类 PrP cTnT 细胞。这些发现表明,ACMs 可以在缺血的人心肌中存活并发育成心肌细胞的亚群。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/971a/5264617/b6bc3af5447b/srep41318-f1.jpg

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