Induction of Pluripotent Stem Cell-Derived Cardiomyocyte Toxicity by Supernatant of Long Term-Stored Red Blood Cells in Vitro
Induction of Pluripotent Stem Cell-Derived Cardiomyocyte Toxicity by Supernatant of Long Term-Stored Red Blood Cells in Vitro
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DOI：
10.1159/00048907
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发表时间：
2018
期刊：
影响因子：
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通讯作者：
Deqing Wang
中科院分区：
文献类型：
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作者：
Fengyan Fan;Yang Yu;Liping Sun;Shufang Wang;Rui Wang;Leiying Zhang;Cuiying Li;Deqing Wang
Background/Aims: Preserved red blood cells (RBCs) in vitro undergo a series of morphological, functional and metabolic changes during storage. RBC metabolites accumulate over time during storage, the toxicity of the supernatants of RBCs (SSRBCs) on tissue cells is largely unknown. Here, we aimed to study cardiomyocyte toxicity by supernatant of long termstored RBCs in vitro and to discover elements involved in the mechanism. Methods: Using human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) and real-time cell analyzing (RTCA), we analyzed the cardiotoxicity of d0, d14 and d35 SSRBCs. To analyze the cardiotoxicity of potassium (K) and lactic acid (LA) in SSRBCs, solutions containing the same concentrations of K and LA were respectively prepared and co-cultured with hiPS-CMs. ,PPXQRÁXRUHVFHQFHDQG*HQH([SUHVVLRQ$UUD\RIKL36&0VZHUHSHUIRUPHGWRHYDOXDWHWKH effects of d35 K and d35 SSRBCs. Results: The beating of hiPS-CM was stopped by d14, d35 SSRBCs, or d35 K solution. Beating resumed within 48 hours in the presence of d14 SSRBC or d35 K but not d35 SSRBC; d0, d14 and d35 LA solution had no effect on beating patterns. At KDIWHUWUHDWPHQWWKHLPPXQRÁXRUHVFHQFHUHVXOWVVKRZHGWKDWWKHLQWHJULW\RIWKHÀODPHQW DQGVDUFRPHUHZHUHLQWDFW*HQH([SUHVVLRQ$UUD\UHVXOWVIRXQGGLIIHUHQWLDOO\H[SUHVVHG genes which were likely to play an important role in the cytotoxic effect. Conclusion: Our results demonstrated cardiomyocyte toxicity by long term-stored SSRBCs in vitro. Besides high K-induced cardiotoxicity, there must be other unknown components in long term-stored SSRBCs that are cytotoxic to hiPS-CMs..
