Rescue of neonatal cardiac dysfunction in mice by administration of cardiac progenitor cells in utero.
Rescue of neonatal cardiac dysfunction in mice by administration of cardiac progenitor cells in utero.
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通过在子宫内施用心脏祖细胞来挽救小鼠新生心脏功能障碍
DOI：
10.1038/ncomms9825
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发表时间：
2015-11-23
影响因子：
16.6
通讯作者：
Perrella MA
中科院分区：
文献类型：
--
作者：
Liu X;Hall SRR;Wang Z;Huang H;Ghanta S;Di Sante M;Leri A;Anversa P;Perrella MA
纹状优先表达基因(SpeG)是肌球蛋白轻链激酶家族的成员。我们之前在小鼠中发现，SpeG基因位点的破坏会导致扩张型心肌病，出现未成熟的心肌细胞。在这里，我们展示了SpeG−/−小鼠的心肌病是由于心脏祖细胞(CpC)功能缺陷引起的，并且通过宫内将野生型CPC注射到SpeG−/−胎儿心脏中可以挽救新生儿的心功能障碍。从SpeG−/−小鼠体内获得的CPC在体外克隆形成、生长和分化为心肌细胞方面存在缺陷，这与体内心脏功能障碍有关。在子宫内将野生型CPC注入SpeG−/−小鼠的心脏，可导致CpC植入、分化和心肌成熟，从而将SpeG−/−小鼠从新生心力衰竭中拯救出来，并使活产儿数量增加5倍。我们认为，宫内给药可能对新生儿心脏病的治疗有未来的意义。SpeG蛋白在发育中的小鼠心脏中表达，在那里它的缺失会导致新生儿心脏病。在这里，作者将SpeG KO小鼠的心肌病追溯到心肌祖细胞(CPC)缺陷，并通过将野生型CPC注射到胎儿心脏来挽救它。
Striated preferentially expressed gene (Speg) is a member of the myosin light chain kinase family. We previously showed that disruption of the Speg gene locus in mice leads to a dilated cardiomyopathy with immature-appearing cardiomyocytes. Here we show that cardiomyopathy of Speg−/− mice arises as a consequence of defects in cardiac progenitor cell (CPC) function, and that neonatal cardiac dysfunction can be rescued by in utero injections of wild-type CPCs into Speg−/− foetal hearts. CPCs harvested from Speg−/− mice display defects in clone formation, growth and differentiation into cardiomyocytes in vitro, which are associated with cardiac dysfunction in vivo. In utero administration of wild-type CPCs into the hearts of Speg−/− mice results in CPC engraftment, differentiation and myocardial maturation, which rescues Speg−/− mice from neonatal heart failure and increases the number of live births by fivefold. We propose that in utero administration of CPCs may have future implications for treatment of neonatal heart diseases. The protein Speg is expressed in the developing mouse heart, where its absence leads to neonatal cardiac disease. Here the authors trace the cardiomyopathy of Speg KO mice back to defects in cardiac progenitor cells (CPCs) and rescue it with injections of wild type CPCs into the foetal heart.