Local and Remote Effects of Mesenchymal Stem Cell Administration on Skin Wound Regeneration

Ekaterina Silina; Victor Stupin; Konstantin Koreyba; Sergey Bolevich; Yulia Suzdaltseva; Natalia Manturova

doi:10.3390/pathophysiology28030024

Local and Remote Effects of Mesenchymal Stem Cell Administration on Skin Wound Regeneration

Pathophysiology. 2021 Aug 12;28(3):355-372. doi: 10.3390/pathophysiology28030024.

Authors

Ekaterina Silina¹, Victor Stupin², Konstantin Koreyba², Sergey Bolevich¹, Yulia Suzdaltseva³, Natalia Manturova⁴

Affiliations

¹ Department of Human Pathology, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia.
² Department of Hospital Surgery №1, N.I. Pirogov Russian National Research Medical University (RNRMU), 117997 Moscow, Russia.
³ Department of Human and Animal Epigenetics, Vavilov Institute of General Genetics of the Russian Academy of Sciences, 119333 Moscow, Russia.
⁴ Department of Plastic and Reconstructive Surgery, Cosmetology and Cell Technologies, N.I. Pirogov Russian National Research Medical University, 117997 Moscow, Russia.

Abstract

Wound healing is an important medical problem. We evaluated the efficacy of locally administered mesenchymal stem cells (MSCs) isolated from human umbilical cords on the dynamics of skin wound healing. The study was conducted on the backs of Wistar rats, where two square wounds were created by removing all layers of the skin. Four groups were studied in two series of experiments: (1) a Control_NaCl group (the wounds were injected with 0.9% NaCl solution) and a Control_0 group (intact wounds on the opposite side of the same rat's back); (2) an MSC group (injected MSCs, local effect) and a Control_sc group (intact wounds on the opposite side of the back, remote MSC effect). The area and temperature of the wounds and the microcirculation of the wound edges were measured. Histological and morphometric studies were performed on days 3 and 7 after the wounds were created. The results showed that the injection trauma (Control_NaCl) slowed the regeneration process. In both MSC groups (unlike in either control group), we observed no increase in the area of the wounds; in addition, we observed inhibition of the inflammatory process and improved wound regeneration on days 1-3 in the remote group and days 1-5 in the local (injected) group. The MSC and Control_sc groups demonstrated improved microcirculation and suppression of leukocyte infiltration on day 3. On day 7, all the studied parameters of the wounds of the Control_0 group were the same as those of the wounds that received cell therapy, although in contrast to the results of the Control_ NaCl group, fibroblast proliferation was greater in the MSC and Control_sc groups. The dynamics of the size of the wounds were comparable for both local and remote application of MSCs. Thus, even a one-time application of MSCs was effective during the first 3-5 days after injury due to anti-inflammatory processes, which improved the regeneration process. Remote application of MSC, as opposed to direct injection, is advisable, especially in the case of multiple wounds, since the results were indistinguishable between the groups and injection trauma was shown to slow healing.

Keywords: fibroblasts; human umbilical cord; inflammation; leukocytes; local and remote stem cell effects; mesenchymal stem cells; regeneration; skin wound; wound healing.