Transplantation of cell sheets from adipose-derived mesenchymal stromal cells effectively induces angiogenesis in ischemic skeletal muscle

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Delivery of cells is a promising approach to induce blood vessel formation for treatment of ischemia. Still, efficacy of these methods has been shown to be below expectations due to the fact that injection procedures used to transplant cells can diminish their survival rate. To circumvent this problem a technique known as “cell sheets” can be utilized. Cell sheets are minimal tissue-engineered constructs that comprise of cells along with their extracellular matrix proteins Present study investigates application of cell sheets from adipose-derived mesenchymal stromal cells (AD-MSC) to stimulate angiogenesis. In a mouse model of limb ischemia we demonstrate that subcutaneous implantation of a cell sheet from 1 mln AD-MSC effectively stimulates angiogenesis and restores perfusion of ischemic muscle compared to untreated animals with limb ischemia. Histology also indicates that cell sheet transplantation results in decreased necrosis of skeletal muscle and retain of AD-MSC at Day 14 with certain prevalence of proliferating and minimal amount of apoptotic cells within cell sheet Furthermore, comparison of cell sheet-treated animals vs. injection of the same dose of AD-MSC shows that cell sheet delivery was superior to routine injection-based delivery in terms of limb perfusion and tissue protection Obtained results indicate that local application of AD-MSC cell sheets to promote angiogenesis and protect skeletal muscle from ischemia can be a promising approach for therapeutic use

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About the authors

P. I Makarevich

Institute of experimental cardiology, Russian cardiology research and production complex Moscow, Russia

M. A Boldyreva

Institute of experimental cardiology, Russian cardiology research and production complex Moscow, Russia

K. V Dergilev

Institute of experimental cardiology, Russian cardiology research and production complex Moscow, Russia

E. V Gluhanyuk

M.V. Lomonosov Moscow state university Moscow, Russia

J. O Gallinger

M.V. Lomonosov Moscow state university Moscow, Russia

A. Yu Efimenko

M.V. Lomonosov Moscow state university Moscow, Russia

V. A Tkachuk

M.V. Lomonosov Moscow state university Moscow, Russia

Ye. V Parfyonova

Institute of experimental cardiology, Russian cardiology research and production complex Moscow, Russia


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