Beckman Sarah A, Sekiya Naosumi, Chen William C W, Mlakar Logan, Tobita Kimimassa, Huard Johnny
Department of Pathology, University of Pittsburgh, Pittsburgh, PA, U.S.A.
Stem Cell Research Center, University of Pittsburgh, Pittsburgh, PA, U.S.A.
CellR4 Repair Replace Regen Reprogram. 2014;2(2). Epub 2014 Mar 31.
Since myoblasts have been limited by poor cell survival after cellular myoplasty, the major goal of the current study was to determine whether improving myoblast survival with an antioxidant could improve cardiac function after the transplantation of the myoblasts into an acute myocardial infarction.
We previously demonstrated that early myogenic progenitors such as muscle-derived stem cells (MDSCs) exhibited superior cell survival and improved cardiac repair after transplantation into infarcted hearts compared to myoblasts, which we partially attributed to MDSC's higher antioxidant levels.
To determine if antioxidant treatment could increase myoblast survival, subsequently improving cardiac function after myoblast transplantation into infarcted hearts.
Myoblasts were pre-treated with the antioxidant N-acetylcysteine (NAC) or the glutathione depleter, diethyl maleate (DEM), and injected into infarcted murine hearts. Regenerative potential was monitored by cell survival and cardiac function.
At early time points, hearts injected with NAC-treated myoblasts exhibited increased donor cell survival, greater cell proliferation, and decreased cellular apoptosis, compared to untreated myoblasts. NAC-treated myoblasts significantly improved cardiac contractility, reduced fibrosis, and increased vascular density compared to DEM-treated myoblasts, but compared to untreated myoblasts, no difference was noted.
While early survival of myoblasts transplanted into infarcted hearts was augmented by NAC pre-treatment, cardiac function remained unchanged compared to non-treated myoblasts.
Despite improving cell survival with NAC treated myoblast transplantation in a MI heart, cardiac function remained similar to untreated myoblasts. These results suggest that the reduced cardiac regenerative potential of myoblasts, when compared to MDSCs, is not only attributable to cell survival but is probably also related to the secretion of paracrine factors by the MDSCs.
由于成肌细胞在细胞性肌成形术后受细胞存活率低的限制，本研究的主要目的是确定用抗氧化剂提高成肌细胞存活率是否能在将成肌细胞移植到急性心肌梗死后改善心脏功能。
我们之前证明，与成肌细胞相比，早期肌源性祖细胞如肌肉衍生干细胞（MDSCs）在移植到梗死心脏后表现出更高的细胞存活率和更好的心脏修复效果，我们将其部分归因于MDSC更高的抗氧化剂水平。
确定抗氧化剂治疗是否能增加成肌细胞存活率，进而在将成肌细胞移植到梗死心脏后改善心脏功能。
成肌细胞用抗氧化剂N-乙酰半胱氨酸（NAC）或谷胱甘肽耗竭剂马来酸二乙酯（DEM）预处理，然后注入梗死的小鼠心脏。通过细胞存活率和心脏功能监测再生潜能。
在早期时间点，与未处理的成肌细胞相比，注射用NAC处理的成肌细胞的心脏表现出供体细胞存活率增加、细胞增殖更多和细胞凋亡减少。与用DEM处理的成肌细胞相比，用NAC处理的成肌细胞显著改善了心脏收缩力、减少了纤维化并增加了血管密度，但与未处理的成肌细胞相比，未观察到差异。
虽然用NAC预处理可提高移植到梗死心脏的成肌细胞的早期存活率，但与未处理的成肌细胞相比，心脏功能没有变化。
尽管在心肌梗死心脏中用NAC处理的成肌细胞移植可提高细胞存活率，但心脏功能与未处理的成肌细胞相似。这些结果表明，与MDSCs相比，成肌细胞心脏再生潜能降低不仅归因于细胞存活率，还可能与MDSCs旁分泌因子的分泌有关。
