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Diabetic genetic background does not influence the isoflurane preconditioning in human cardiomyocytes differentiated from induced pluripotent stem cells derived from a type 1 diabetes patient
Author(s) -
Kikuchi Chika,
Canfield Scott,
Bai Xiaowen,
Koopmeiners Andrew,
Kwok Wai-Meng,
Schaefer Richard,
Bosnjak Zeljko
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.678.20
Subject(s) - induced pluripotent stem cell , isoflurane , type 1 diabetes , anesthetic , oxidative stress , medicine , lactate dehydrogenase , reperfusion injury , ischemic preconditioning , microbiology and biotechnology , pharmacology , ischemia , chemistry , diabetes mellitus , embryonic stem cell , anesthesia , biology , endocrinology , biochemistry , enzyme , gene
Anesthetic preconditioning (APC) has been proved to increase myocardial tolerance to ischemia reperfusion injury. However, growing evidence shows that APC is attenuated in diabetes. The generation of induced pluripotent stem cells (iPSCs) enabled the production of patient specific cardiomyocytes (CMs), providing a novel model to study the roles of diabetic genetic background and environmental factors in the attenuation of APC. iPSCs generated from a healthy donor and a T1DM patient were directly differentiated into CMs (N‐iPSC‐CMs and T1DM‐iPSC‐CMs, respectively). The differentiated CMs were confirmed by the expression of CM‐specific markers troponin T and sarcomeric á‐actinin and the presence of action potentials. Lactate dehydrogenase (LDH) release assay was then performed to determine the viability with or without isoflurane preconditioning in response to oxidative stress. The isoflurane preconditioning decreased LDH release in both N‐iPSC‐CMs and T1DM‐iPSC‐CMs in response to oxidative stress. iPSCs generated from both the healthy donor and the T1DM patient can differentiate into functional cardiomyocytes. Importantly, our results show that isoflurane can precondition both N‐iPSC‐CMs and T1DM‐iPSC‐CMs, suggesting that genetic factors may not play major roles in the attenuation of APC. P01GM066730 and R01HL034708 from the NIH, Bethesda, MD (to Z. Bosnjak).