Umbilical cord-derived mesenchymal stromal/stem cells enhance recovery of surgically induced skeletal muscle ischemia in a rat model
Irina Arutyunyan1,2, Timur Fatkhudinov1,2, Andrey Elchaninov1,2, Olesya Vasyukova3, Andrey Makarov1,4, Natalia Usman1, Evgeniya Kananykhina1,3, Anastasiya Lokhonina1,3, Dmitry Goldshtein5, Galina Bolshakova3 and Gennady Sukhikh1
1National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of Ministry of Healthcare of Russian Federation, 2Peoples' Friendship University of Russia (RUDN University), 3Scientific Research Institute of Human Morphology, 4Pirogov Russian National Research Medical University, Ministry of Healthcare of the Russian Federation and 5Research Centre of Medical Genetics of the Russian Academy of Medical Sciences, Moscow, Russian Federation
Offprint requests to: Dr. T. Fatkhudinov, Laboratory of Regenerative Medicine, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of Ministry of Healthcare of Russian Federation, 4 Oparin Street, Moscow, 117997, Russian Federation. e-mail: tfat@yandex.ru
Summary. This study delves into possible mechanisms underlying the stimulating influence of UC-MSCs transplantation on functional and structural recovery of ischemic skeletal muscles. Limb ischemia was created in Sprague-Dawley rats by excision of femoral and popliteal arteries. Allogeneic rat PKH26-labeled UC-MSCs were administered by direct intramuscular injection. Animals of experimental group responded to the transplantation by improvement in their locomotor function as assessed by the rotarod performance test on day 9 and 29 after transplantation. Histomorphometric analysis showed that relative area of the lesions in the experimental group was significantly smaller than in the control group at all time points during the observation. Calculated densities of microcirculation vessels within the lesions were significantly higher in the experimental group than in the control group on day 10 after transplantation. Only a part of the transplanted allogeneic UC-MSCs survived within the ischemic muscle tissue, and a considerable portion of these surviving cells were found alongside the VEGF-producing preserved muscle fibers. The PKH26 label was not found within the walls of capillaries or larger blood vessels. The administration of allogeneic UC-MSCs significantly increased the proportion of M2 macrophages, exhibiting proangiogenic and anti-inflammatory properties, for at least 10 days following the transplantation. Histol Histopathol 34, 513-523 (2019)
Key words: Umbilical cord-derived mesenchymal stromal/stem cells, Allogeneic transplantation, Muscle ischemia, Revascularization, M2 macrophage activation
DOI: 10.14670/HH-18-057