| Autor: |
Dergilev KV; National Medical Research Center of Cardiology, Russian Ministry of Health, Moscow 121552, Russia., Shevchenko EK; National Medical Research Center of Cardiology, Russian Ministry of Health, Moscow 121552, Russia.; Federal Center of Brain Research and Neurotechnologies, Federal Medical Biological Agency, Moscow 117997, Russia., Tsokolaeva ZI; National Medical Research Center of Cardiology, Russian Ministry of Health, Moscow 121552, Russia.; Research Institute of General Reanimatology, Russian Academy of Medical Sciences, Moscow 107031, Russia., Beloglazova IB; National Medical Research Center of Cardiology, Russian Ministry of Health, Moscow 121552, Russia., Zubkova ES; National Medical Research Center of Cardiology, Russian Ministry of Health, Moscow 121552, Russia., Boldyreva MA; National Medical Research Center of Cardiology, Russian Ministry of Health, Moscow 121552, Russia., Menshikov MY; National Medical Research Center of Cardiology, Russian Ministry of Health, Moscow 121552, Russia., Ratner EI; National Medical Research Center of Cardiology, Russian Ministry of Health, Moscow 121552, Russia., Penkov D; National Medical Research Center of Cardiology, Russian Ministry of Health, Moscow 121552, Russia., Parfyonova YV; National Medical Research Center of Cardiology, Russian Ministry of Health, Moscow 121552, Russia.; Faculty of Medicine, Lomonosov Moscow State University, Moscow 119991, Russia. |
| Abstrakt: |
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. |
