Survival and functional activity examination of cardiomyocytes differentiated from human iPSCs, when transplanting in SCID mice

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Abstract

Conduction and heart rhythm disorders can be caused by both functional pathology and severe organic lesions of the heart. The possibility of using cell-based replacement cell therapy derived from induced pluripotent stem cells to compensate for lost myocardial tissue or the conduction system is currently being studied. The aim of the work is to study the survival and functional activity of cardiomyocytes differentiated from induced human pluripotent stem cells in intramyocardial and subcutaneous abdominal transplantation in a clots of proteins of the basement membrane matrix Matrigel to the SCID mice. After 2 and 5 weeks after intramyocardial and 2, 7, 14, 21 and 28 days after subcutaneous transplantation, the survival and activity of cardiomyocytes were studied by cytological methods. Human cardiomyocytes were detected in mice for at least 35 days. after transplantation and did not cause ectopic electrical activity of the myocardium. When assessing the functional activity of cardiomyocytes in subcutaneous matrigel plugs using the method of optical mapping of calcium ion currents for 2-28 days. after injection, it was shown that only a small fraction of cardiomyocytes after transplantation was able to spontaneously oscillate the calcium ions. We assume that contractile cardiomyocytes obtained from induced pluripotent human cells lose their ability to spontaneous excitation during in vivo transplantation, and we observe only the activity of pacemaker cardiomyocytes in optical mapping.

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About the authors

S. V Pavlova

Federal Research Center Institute of Cytology and Genetics of the SO of the RAS; E.N. Meshalkin National Medical Research Center; Institute of Chemical Biology and Fundamental Medicine of the SO of the RAS

Email: sonpavlova@gmail.com

E. V Chepeleva

E.N. Meshalkin National Medical Research Center

E. V Dementyeva

Federal Research Center Institute of Cytology and Genetics of the SO of the RAS; E.N. Meshalkin National Medical Research Center; Institute of Chemical Biology and Fundamental Medicine of the SO of the RAS

E. V Grigor'eva

Federal Research Center Institute of Cytology and Genetics of the SO of the RAS; E.N. Meshalkin National Medical Research Center; Institute of Chemical Biology and Fundamental Medicine of the SO of the RAS; Novosibirsk State University

E. D Sorokoumov

Institute of Computational Technologies of the SO of the RAS

M. M Slotvitsky

Moscow Institute of Physics and Technology (State University)

A. V Ponomarenko

E.N. Meshalkin National Medical Research Center

A. A Dokuchaeva

E.N. Meshalkin National Medical Research Center

A. A Malakhova

Federal Research Center Institute of Cytology and Genetics of the SO of the RAS; E.N. Meshalkin National Medical Research Center; Institute of Chemical Biology and Fundamental Medicine of the SO of the RAS; Novosibirsk State University

D. S Sergeevichev

E.N. Meshalkin National Medical Research Center

E. A Pokushalov

E.N. Meshalkin National Medical Research Center

S. M Zakian

Federal Research Center Institute of Cytology and Genetics of the SO of the RAS; E.N. Meshalkin National Medical Research Center; Institute of Chemical Biology and Fundamental Medicine of the SO of the RAS; Novosibirsk State University

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