Characterization and functionality of cardiac progenitor cells in congenital heart patients.
Characterization and functionality of cardiac progenitor cells in congenital heart patients.
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DOI：
10.1161/circulationaha.110.971622
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发表时间：
2011-02-01
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：
Mishra R;Vijayan K;Colletti EJ;Harrington DA;Matthiesen TS;Simpson D;Goh SK;Walker BL;Almeida-Porada G;Wang D;Backer CL;Dudley SC Jr;Wold LE;Kaushal S
人心脏祖细胞（hCPCs）可促进成人缺血心肌的再生。在非缺血性先天性心脏病的年轻患者中，hCPCs的再生能力在先天性心脏病修复中的潜在用途值得探索。在常规先天性心脏病手术期间，采集了3组人右心房样本：新生儿（年龄，<30天）、婴儿（年龄，1个月至2岁）和儿童（年龄，>2至≤13岁）。新生儿中的C-kit+ hCPCs是>2岁儿童的3倍。c-kit+ Ki 67+表达证实hCPC增殖在新生期最大，但随着年龄的增长而下降。hCPC分化能力在新生儿右心房中也最大，如c-kit+、NKX 2 -5+、NOTCH 1+和NUMB+表达所证明。尽管居民hCPC的年龄依赖性下降，我们使用cardiosphere方法从所有年龄和诊断的所有患者（n = 103）中分离和扩增右心房来源的CPC。完整的心脏微球含有心脏来源的细胞亚群的混合物，包括表达c-kit+、Islet-1和支持细胞的心脏祖细胞。c-kit+表达细胞的数量在从新生儿和婴儿右心房生长的人心球衍生细胞（hCDC）中最高。此外，通过体外分化测定，hCDC可以分化成不同的心血管谱系。移植的hCDCs比移植的心脏成纤维细胞更能促进梗死心肌的心肌再生和功能改善。常驻hCPC在新生儿期最丰富，并随时间迅速减少。hCDC可以从年轻人心肌样品中可重复地分离和扩增，无论年龄或诊断如何。hCPC是功能性的，并且在先天性心脏修复中具有潜力。
Human cardiac progenitor cells (hCPCs) may promote myocardial regeneration in adult ischemic myocardium. The regenerative capacity of hCPCs in young patients with nonischemic congenital heart defects for potential use in congenital heart defect repair warrants exploration. Human right atrial specimens were obtained during routine congenital cardiac surgery across 3 groups: neonates (age, <30 days), infants (age, 1 month to 2 years), and children (age, >2 to ≤13 years). C-kit+ hCPCs were 3-fold higher in neonates than in children >2 years of age. hCPC proliferation was greatest during the neonatal period as evidenced by c-kit+ Ki67+ expression but decreased with age. hCPC differentiation capacity was also greatest in neonatal right atrium as evidenced by c-kit+, NKX2–5+, NOTCH1+, and NUMB+ expression. Despite the age-dependent decline in resident hCPCs, we isolated and expanded right atrium–derived CPCs from all patients (n = 103) across all ages and diagnoses using the cardiosphere method. Intact cardiospheres contained a mix of heart-derived cell subpopulations that included cardiac progenitor cells expressing c-kit+, Islet-1, and supporting cells. The number of c-kit+–expressing cells was highest in human cardiosphere-derived cells (hCDCs) grown from neonatal and infant right atrium. Furthermore, hCDCs could differentiate into diverse cardiovascular lineages by in vitro differentiation assays. Transplanted hCDCs promoted greater myocardial regeneration and functional improvement in infarcted myocardium than transplanted cardiac fibroblasts. Resident hCPCs are most abundant in the neonatal period and rapidly decrease over time. hCDCs can be reproducibly isolated and expanded from young human myocardial samples regardless of age or diagnosis. hCPCs are functional and have potential in congenital cardiac repair.