Cell Sheet Comprised of Mesenchymal Stromal Cells Overexpressing Stem Cell Factor Promotes Epicardium Activation and Heart Function Improvement in a Rat Model of Myocardium Infarction |
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Authors: | Konstantin V. Dergilev Evgeny K. Shevchenko Zoya I. Tsokolaeva Irina B. Beloglazova Ekaterina S. Zubkova Maria A. Boldyreva Mikhail Yu. Menshikov Elizaveta I. Ratner Dmitry Penkov Yelena V. Parfyonova |
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Affiliation: | 1.National Medical Research Center of Cardiology, Russian Ministry of Health, Moscow 121552, Russia; (K.V.D.); (Z.I.T.); (I.B.B.); (E.S.Z.); (M.A.B.); (M.Y.M.); (E.I.R.); (D.P.); (Y.V.P.);2.Federal Center of Brain Research and Neurotechnologies, Federal Medical Biological Agency, Moscow 117997, Russia;3.Research Institute of General Reanimatology, Russian Academy of Medical Sciences, Moscow 107031, Russia;4.Faculty of Medicine, Lomonosov Moscow State University, Moscow 119991, Russia |
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Abstract: | Cell therapy of the post-infarcted myocardium is still far from clinical use. Poor survival of transplanted cells, insufficient regeneration, and replacement of the damaged tissue limit the potential of currently available cell-based techniques. In this study, we generated a multilayered construct from adipose-derived mesenchymal stromal cells (MSCs) modified to secrete stem cell factor, SCF. In a rat model of myocardium infarction, we show that transplantation of SCF producing cell sheet induced activation of the epicardium and promoted the accumulation of c-kit positive cells in ischemic muscle. Morphometry showed the reduction of infarct size (16%) and a left ventricle expansion index (0.12) in the treatment group compared to controls (24–28%; 0.17–0.32). The ratio of viable myocardium was more than 1.5-fold higher, reaching 49% compared to the control (28%) or unmodified cell sheet group (30%). Finally, by day 30 after myocardium infarction, SCF-producing cell sheet transplantation increased left ventricle ejection fraction from 37% in the control sham-operated group to 53%. Our results suggest that, combining the genetic modification of MSCs and their assembly into a multilayered construct, we can provide prolonged pleiotropic effects to the damaged heart, induce endogenous regenerative processes, and improve cardiac function. |
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Keywords: | stem cell factor adipose derived mesenchymal stromal cells cell sheet myocardial infarction heart function |
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