Histological and Immunohistochemical Study on the Role of Mesenchymal Stem Cells in the Repair of Experimentally Induced Skin Burn in Adult Male Albino Rat

Abstract

The skin is considered to be the largest organ in the human body. It forms the barrier that protects our internal environment from pathogens and plays a major role in thermoregulation. Deep burns are non-healing wounds that involve the full thickness of the skin and deeper structures. They are among the greatest challenges to treat in medicine. An ideal therapy would promote the rapid healing process and also avoids the development of a scar. In the last years, MSCs have been efficiently used to treat several conditions, such as hematological and immunomediated diseases, heart dysfunctions, bone injury and skin ulcers, both in experimental animal models and humans. Mesenchymal stem cells can be isolated from many tissue sources such as bone marrow. The current experiment was carried out to study the use of bone marrow derived MSCs in the repair of skin burn injury in adult male albino rats. Forty adult male albino rats of average weight 200 grams were used in this experiment. In addition to five young male albino rats of average weight 100 grams served as a source of bone marrow from which stem cells were derived. The forty adult rats were divided into four main groups  Group I: served as a control group.  Group II: served as a full thickness burn model.  Group III: was subdivided into subgroups IIIA, IIIB and IIIC. Skin burn was induced on the back of the rats. The rats were sacrificed 7, 14 and 21 days post burn respectively.  Group IV: was subdivided into subgroups IVA, IVB and IVC. Skin burn was induced on the back of the rats and PKH26 labelled BM-MSCs were injected intra-dermally around the burned skin area. Rats were sacrificed after 7, 14 and 21 days respectively. Skin specimens from each group were examined histologically and immunohistochemically. Morphometric study was done on size of the wound, epidermal thickness, dermal thickness, collagen area percentage and α-SMA reaction density and confirmed with statistical analysis. The size of the wound was significantly decreased starting from 7 days after the BM-MSCs injection. The wound was almost completely covered by epidermis after 21 days from injection of the BM-MSCs and showed re-growth of hair follicles. The epidermal thickness showed significant thinning in the burn model group II which was represented by exfoliation of the upper layers and flattening of the basal layer of epidermis. The epidermis was lost for 14 days after burn induction (subgroup IIIA and subgroup IIIB). Twenty-one days after burn induction some areas showed the beginning of spontaneous regeneration represented by spindle shaped cells covering the dermis. After 7 days from BM-MSCs injection, there was preservation of a thin epidermis. After 14 days, the epidermis showed complete regeneration of its 4 layers with significantly increased thickness. After 21 days from BM-MSCs injection, the epidermal thickness was almost similar to the control group. Dermal thickness showed significant decrease in the untreated group III due to partial loss of the papillary dermis. After 21 days from BM-MSCs injection (subgroup IVC), the dermal thickness was almost equal to that of the control group. Moreover, the BM-MSCs injected group IV showed a significant increase in collagen area percentage in comparison to the untreated group III.