Safety and effectiveness evaluation of the injection transplantation method of human pacemaker cardiomyocyte derived from induced pluripotent stem cells

Cover Page


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Arrhythmia is a pathological condition leading to a violation of the frequency, rhythm and sequence of the heart contraction. The cell therapy methods open a new possibility for this group of diseases treatment. This work was aimed to evaluate effectiveness and safeness of cardiomyocytes transplantation in the heart of laboratory animals. In the experiment, two groups of animals were examined: in the first group injection of cardiomyocytes contained in Matrigel was made into the wall of the left ventricle, saline injection was performed in the second group. To reduce the rejection reaction after xenogeneic cell culture transplantation prior to surgery and during the whole observation period, the animals were immunosuppressed by cyclosporin A and prednisolone combination. Electrocardiogram was recorded daily during the postoperative follow-up period to catch the ectopic events. After 5 days from cells transplantation animals were euthanized, the myocardium with transplanted material was taken for histological and immunohistochemical analysis. In the course of the work, it was shown that transplanted cardiomyocytes persist in the heart of experimental animals up to 5 days, but no electrophysiological activity was found. The obtained data indicate the need for additional experimental work with increased immunosuppression, increased time of the cells in the myocardium, an increase in the percentage of pacemaker cells in the used culture.

Full Text

Restricted Access

About the authors

A. V Ponomarenko

E.N. Meshalkin National Medical Research Center

E. V Chepeleva

E.N. Meshalkin National Medical Research Center

S. V Pavlova

E.N. Meshalkin National Medical Research Center

A. B Romanov

E.N. Meshalkin National Medical Research Center

A. G Strelnikov

E.N. Meshalkin National Medical Research Center

D. S Sergeevichev

E.N. Meshalkin National Medical Research Center

Email: d_sergeevichev@meshalkin.ru

E. A Pokushalov

E.N. Meshalkin National Medical Research Center

References

  1. Boyett M.R., Honjo H., Kodama I. The sinoatrial node, a heterogeneous pacemaker structure. Cardiovasc. Res. 2000; 47(4): 658-87.
  2. Chugh S.S., Reinier K., Teodorescu C. et al. Epidemiology of sudden cardiac death: clinical and research implication. Prog. Cardiovasc. 2008; 51: 213-28.
  3. Adan V., Crown L.A. Diagnosis and treatment of sick sinus syndrome. Am. Fam. Physician. 2003; 67: 1725-32.
  4. Inoue S., Shinohara F., Sakai T. et al. Myocarditis and arrhythmia: a clinico-pathological study of conduction system based on serialsection in 65 cases. Jpn. Circ. J. 1989; 53: 49-57.
  5. Milano A., Vermeer A.M., Lodder E.M. et al. HCN4 mutations in multiple families with bradycardia and left ventricular noncompaction cardiomyopathy. J. Am. Coll. Cardiol. 2014; 64: 745-56.
  6. Balijepalli R.C., Kamp T.J. Caveolae, ion channels and cardiac arrhythmias. Prog. Biophys. Mol. Biol. 2008; 98: 149-60.
  7. Lei M., Zhang H., Grace A.A. SCN5A and sinoatrial node pacemaker function. Cardiovasc. Res. 2007; 74: 356-65.
  8. Poole J.E., Gleva M.J., Mela T. et al. Complication rates associated with pacemaker or implantable cardioverter-defibrillator generator replacements and upgrade procedures clinical perspective: results from the REPLACE Registry. Circulation 2010; 122(16): 1553-61.
  9. Takahashi K., Tanabe K., Ohnuki M. et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007; 131(5): 861-72.
  10. Boheler K.R., Czyz J., Tweedie D. et al. Differentiation of pluripotent embryonic stem cells into cardiomyocytes. Circ. Res. 2002; 91(3): 189-201.
  11. Lian X., Zhang J., Azarin S.M. et al. Directed cardiomyocyte differentiation from human pluripotent stem cells by modulating Wnt/β-catenin signaling under fully defined conditions. Nat. Protoc. 2013; 8(1): 162-75.
  12. Zhang H., Lau D.H., Shlapakova I.N. et al. Implantation of sinoatrial node cells into canine right ventricle: biological pacing appears limited by the substrate. Cell Transplant. 2011; 20: 1907-14.
  13. Zhang L., Li X., Yu X. et al. Construction of vascularized pacemaker tissues by seeding cardiac progenitor cells and endothelial progenitor cells into Matrigel. Life Sciences 2017; 179: 139-46.
  14. Xia X., Li J., Xia B. et al. Matrigel scaffold combined with Ad-hBMP7-transfected chondrocytes improves the repair of rabbit cartilage defect. Exp. Ther. Med. 2017; 13(2): 542-50.
  15. Burridge P.W., Matsa E., Shukla P. et al. Chemically defined generation of human cardiomyocytes. Nature methods 2014; 11(8): 855-60.
  16. Худяков А.А., Курапеев Д.И., Костарева А.А. и др. Сравнение эффективности методов получения функционально активных кардиомиоцитов человека. Гены и Клетки 2013; 8(2): 47-55.
  17. Милевская Е.А., Немудрый А.А., Чепелева Е.В. и др. Оптимизация протокола интрамиокардиальной трансплантации с использованием люминесценции кардиальных мезенхимальных клеток, маркированных экспрессией люциферазы. Патология кровообращения и кардиохирургия 2015; 19(4-2): 69-77.
  18. Павлова С.В., Леонова Е.А., Чепелева Е.В. и др. Мониторинг трансплантации кардиальных клеток в зону ишемического повреждения миокарда с использованием люциферазной репортерной системы. Гены и Клетки 2017; 12(4): 69-75.

Supplementary files

Supplementary Files
Action
1. JATS XML

Copyright (c) 2018 Eco-Vector



СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: 

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies