Division of Cardiac Surgery, University of Maryland, Baltimore, MD, USA.
Circulation. 2012 Sep 11;126(11 Suppl 1):S46-53. doi: 10.1161/CIRCULATIONAHA.111.084699.
Human cardiac stem cells (CSCs) promote myocardial regeneration in adult ischemic myocardium. The regenerative capacity of CSCs in very young patients with nonischemic 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 2 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 with adult-derived CDCs. Last, neonatal-derived CDCs were more cardiomyogenic than adult-derived CDCs when cocultured with neonatal cardiomyocytes and displayed enhanced angiogenic function compared with adult-derived CDCs.
Neonatal-derived CDCs have a strong regenerative ability when compared with 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.
人类心脏干细胞（CSC）可促进成人缺血性心肌的再生。尚未探索非缺血性先天性心脏缺陷的非常年幼患者中 CSC 的再生能力。我们假设分离的新生儿来源的 CSC 可能比成人来源的 CSC 具有更高的再生能力，并且可能解决先天性心脏病的结构缺陷。
我们从 2 个年龄组的右心房附件组织中获得了人类标本：新生儿和成年患者。我们开发了一种可重复的分离方法，可产生心脏球源性细胞（CDCs），而与起始组织重量或年龄无关。通过流式细胞术和免疫荧光法，新生儿来源的 CDCs 显示出表达 c-kit（+），flk-1 和 Islet-1 的心脏祖细胞数量增加。当移植到梗塞的心肌中时，与成年来源的 CDCs 相比，新生儿来源的 CDCs 具有更高的保存心肌功能，预防不良重塑以及增强血管保存和/或形成的能力。最后，与新生儿心肌细胞共培养时，新生儿来源的 CDCs 比成年来源的 CDCs 具有更强的心肌生成能力，并且与成年来源的 CDCs 相比具有增强的血管生成功能。
与成年来源的 CDCs 相比，新生儿来源的 CDCs 具有更强的再生能力，这可能取决于血管生成细胞因子和干细胞的增加。这对将来在临床试验中使用 CDCs 具有重要意义。
