A strong regenerative ability of cardiac stem cells derived from neonatal hearts.
A strong regenerative ability of cardiac stem cells derived from neonatal hearts.
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DOI：
10.1161/circulationaha.111.084699
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发表时间：
2012-09-11
期刊：
影响因子：
37.8
通讯作者：
Kaushal S
中科院分区：
文献类型：
--
作者：
Simpson DL;Mishra R;Sharma S;Goh SK;Deshmukh S;Kaushal S
人干细胞（CSCs）促进成人缺血心肌再生。在非缺血性先天性心脏病的非常年轻的患者中，CSC的再生能力尚未被探索。我们假设，分离的胎盘来源的CSC可能比成人来源的CSC具有更高的再生能力，并可能解决先天性心脏病的结构缺陷。在常规心脏外科手术过程中，从两个年龄组（新生儿和成人患者）丢弃的右心耳组织中获得人体样本。我们开发了一种可重复的分离方法，产生心脏球衍生细胞（CDC），无论起始组织重量或年龄。通过流式细胞术和免疫荧光检测，新生儿来源的CDC显示表达c-kit+、flk-1和Islet-1的心脏祖细胞数量增加。当移植到梗死心肌中时，与成人CDC相比，血管来源的CDC具有显著更高的保护心肌功能、防止不良重塑和增强血管保存和/或形成的能力。最后，当与新生儿心肌细胞共培养时，胎盘来源的CDCs比成人CDCs更具心肌源性，并且与成人CDCs相比显示出增强的血管生成功能。与成人来源的CDC相比，新生儿来源的CDC具有很强的再生能力，这可能依赖于血管生成细胞因子和干细胞的增加。这对CDC在未来临床试验中的潜在应用具有重要意义。
Human stem cells (CSCs) promote myocardial regeneration in adult ischemic myocardium. The regenerative capacity of CSCs in the very young patients with non-ischemic congenital heart defects has not been explored. We hypothesized that isolated neonatal-derived CSCs may have a higher regenerative ability than adult-derived CSCs and might address the structural deficiencies of congenital heart disease. Human specimens were obtained during routine cardiac surgical procedures from right atrial appendage tissue discarded from two age groups: neonates and adults patients. We developed a reproducible isolation method that generated cardiosphere derived cells (CDCs), regardless of starting tissue weight or age. Neonatal-derived CDCs demonstrated increased number of cardiac progenitor cells expressing c-kit+, flk-1 and Islet-1 by flow cytometry and immunofluorescence. When transplanted into infarcted myocardium, neonatal-derived CDCs had a significantly higher ability to preserve myocardial function, prevent adverse remodeling and enhance blood vessel preservation and/or formation when compared to adult CDCs. Lastly, neonatal-derived CDCs were more cardiomyogenic than adult CDCs when co-cultured with neonatal cardiomyocytes and displayed enhanced angiogenic function compared to adult CDCs. Neonatal-derived CDCs have a strong regenerative ability when compared to adult-derived CDCs that may depend on angiogenic cytokines and an increase prevalence of stem cells. This has important implications in the potential use of CDCs in future clinical trials.