人诱导多能干细胞来源的心肌细胞在新生和成年大鼠心脏中的体内成熟
In Vivo Maturation of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes in Neonatal and Adult Rat Hearts.
作者信息
Kadota Shin, Pabon Lil, Reinecke Hans, Murry Charles E
机构信息
Department of Pathology, University of Washington, 850 Republican Street, Brotman Building Room 453, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98109, USA; Center for Cardiovascular Biology, University of Washington, Seattle, WA 98109, USA.
Department of Pathology, University of Washington, 850 Republican Street, Brotman Building Room 453, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98109, USA; Center for Cardiovascular Biology, University of Washington, Seattle, WA 98109, USA; Department of Bioengineering, University of Washington, Seattle, WA 98109, USA; Department of Medicine/Cardiology, University of Washington, Seattle, WA 98109, USA.
出版信息
Stem Cell Reports. 2017 Feb 14;8(2):278-289. doi: 10.1016/j.stemcr.2016.10.009. Epub 2017 Jan 5.
We hypothesized that the neonatal rat heart would bring transplanted human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to maturity as it grows to adult size. In neonatal rat heart, engrafted hiPSC derivatives developed partially matured myofibrils after 3 months, with increasing cell size and sarcomere length. There was no difference between grafts from hiPSC-CMs or hiPSC-derived cardiac progenitors (hiPSC-CPs) at 3 months, nor was maturation influenced by infarction. Interestingly, the infarcted adult heart induced greater human cardiomyocyte hypertrophy and induction of cardiac troponin I expression than the neonatal heart. Although human cardiomyocytes at all time points were significantly smaller than the host rat cardiomyocytes, transplanted neonatal rat cardiomyocytes reached adult size and structure by 3 months. Thus, the adult rat heart induces faster maturation than the neonatal heart, and human cardiomyocytes mature more slowly than rat cardiomyocytes. The slower maturation of human cardiomyocytes could be related to environmental mismatch or cell-autonomous factors.
我们推测，新生大鼠心脏在生长至成年大小时，会使移植的人诱导多能干细胞来源的心肌细胞（hiPSC-CMs）成熟。在新生大鼠心脏中，移植的hiPSC衍生物在3个月后形成了部分成熟的肌原纤维，细胞大小和肌节长度增加。3个月时，来自hiPSC-CMs或hiPSC来源的心脏祖细胞（hiPSC-CPs）的移植物之间没有差异，梗死也不影响成熟。有趣的是，梗死的成年心脏比新生心脏诱导更大程度的人类心肌细胞肥大和心肌肌钙蛋白I表达的诱导。尽管所有时间点上的人类心肌细胞都明显小于宿主大鼠心肌细胞，但移植的新生大鼠心肌细胞在3个月时达到了成年大小和结构。因此，成年大鼠心脏比新生心脏诱导更快的成熟，而人类心肌细胞比大鼠心肌细胞成熟得更慢。人类心肌细胞成熟较慢可能与环境不匹配或细胞自主因素有关。
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