Adipose-derived stem cells improve full-thickness skin grafts in a rat model

• Published in: Research in veterinary science Vol. 118; pp. 336 - 344
• Main Authors: Vidor, Silvana Bellini, Terraciano, Paula Barros, Valente, Fernanda Soldatelli, Rolim, Verônica Machado, Kuhl, Cristiana Palma, Ayres, Laura Silveira, Garcez, Tuane Nerissa Alves, Lemos, Natália Emerim, Kipper, Cristiano Ely, Pizzato, Sabrina Beal, Driemeier, David, Cirne-Lima, Elizabeth Obino, Contesini, Emerson Antonio
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.06.2018; Elsevier Limited
• Subjects: Adipocytes - cytology; Adipose Tissue - cytology; Angiogenesis; Animals; Autografts; Cell therapy; Collagen; Contraction; Cytokines; Degeneration; Dermis; Disease Models, Animal; Dressings; Epidermis; Follicles; Gangrene; Grafting; Grafts; Granulation; Growth factors; Hair; Hypoxia; Immunohistochemistry; Inflammation; Injury prevention; Ischemia; Ischemia and reperfusion injury; Keratosis; Laboratory animals; Motivation; Plastic surgery; Rats; Rats, Wistar; Reconstructive surgery; Regenerative therapy; Reperfusion; Rodents; Saline solutions; Skin; Skin & tissue grafts; Skin grafts; Skin Transplantation; Staining; Stem Cell Transplantation; Stem Cells; Studies; Thickening; Tissue Engineering; Vascular endothelial growth factor; Veterinary medicine; Wound Healing; Brazil; United States > US; Cell therapy; Regenerative therapy; Reconstructive surgery; Ischemia and reperfusion injury
• ISSN: 0034-5288; 1532-2661
• DOI: 10.1016/j.rvsc.2018.03.014

To investigate the effects of heterologous adipose-derived stem cells (ADSCs) on autologous full-thickness skin grafts, we designed a first-intention healing model using Wistar rats. We harvested and sutured two full-thickness skin grafts in the dorsal recipient beds of 15 rats, randomized into three groups. In the treatment group, 1 × 106 ADSCs resuspended in saline solution (200 μL) were administered subcutaneously to the skin graft. The control group received only saline solution subcutaneously, whereas the negative control group did not receive any treatment. Compressive dressings were maintained until postoperative day 5. The grafts were assessed by two observers, who checked for the presence of epidermolysis on day 14. Planimetry showed the relative areas of normal skin, redness, ulceration, and contraction. Graft samples were obtained on day 14 and stained with hematoxylin and eosin and Masson's trichrome. Epidermal analysis evaluated thickening, keratosis, acanthosis, hydropic degeneration, and inflammatory infiltrate. Dermal evaluation investigated the absence of hair follicles, granulation tissue formation, presence of inflammatory infiltrate, and collagen deposition. Immunohistochemistry was performed for dermal anti-VEGF and epidermal anti-Ki-67 staining. The ADSC group presented better macroscopic aspects, lower incidence of epidermolysis, and less loss of hair follicles. In addition, the ADSC group presented the lowest frequency of histopathological changes in the dermis and epidermis, as well as the largest subcutaneous and granulation tissue VEGF averages and the weakest Ki-67 staining of the epidermal basal layer. Subcutaneous administration of ADSCs may improve the integration of skin grafts, reducing the deleterious effects of ischemia and reperfusion injury. •Subcutaneous ADSC administration in skin grafts may improve their integration.•ADSCs reduce epidermolysis and histological changes in full-thickness skin grafts.•The morphology of ADSC-treated grafts resembled that of the adjacent healthy skin in postoperative period.