Adipose stem cells enhance excisional wound healing in a porcine model

• Published in: The Journal of surgical research 2018-09, Vol.229, p.243-253
• Main Authors: James, Isaac, Bourne, Debra, Silva, Mayara, Havis, Emmanuelle, Albright, Kassandra, Zhang, Liyong, Kostereva, Nataliya, Wang, Sheri, DiBernardo, Gabriella, Guest, Rachel, Lei, Jenny, Almadori, Aurora, Satish, Latha, Marra, Kacey, Rubin, J. Peter
• Format: Article
• Language: English
• Subjects: Adipose stem cell; Adipose Tissue - cytology; Animals; ASC; Cell Differentiation; Cicatrix - etiology; Cicatrix - prevention & control; Disease Models, Animal; Excisional wounds; Female; Humans; Intercellular Signaling Peptides and Proteins - metabolism; Life Sciences; Neovascularization, Physiologic - physiology; Pig model; Porcine model; Regeneration - physiology; Skin - blood supply; Skin - injuries; Stem Cell Transplantation - methods; Stem Cells - physiology; Sus scrofa; Wound healing; Wound Healing - physiology; Wounds, Penetrating - complications; Wounds, Penetrating - therapy
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2018.03.068

Adipose-derived stem cells (ASCs) are capable of secreting regenerative growth factors and replacing multiple tissue types. Although current literature suggests that ASCs accelerate wound healing and reduce scarring, the dose-response relationship has not been adequately investigated in large animals. We sought to establish a porcine model to optimize dose and delivery. Four-centimeter circular, full thickness excisional wounds were created on the backs of Yorkshire pigs. Fluorescently labeled allogeneic porcine ASCs were injected into the superficial wound bed and around the wound perimeter at high (3.0 × 106 cells/cm2; n = 8), medium (1.0 × 106 cells/cm2; n = 8), and low (0.3 × 106 cells/cm2; n = 8) doses. Control wounds received saline injections (n = 8) or no treatment (n = 8). Dressings were changed twice per week, and wound closure was tracked by surface area tracing. Animals were sacrificed at 1 and 2 wk. Wounds were harvested for real-time quantitative reverse transcriptase polymerase chain reaction, immunohistochemistry, and ASC tracking. Labeled ASCs integrated into treated wounds by 1 wk in a dose-dependent fashion. Epithelial coverage was achieved by 14 d in all wounds. Wounds receiving high-dose ASCs exhibited thicker granulating neodermis at 7 d and greater wound contraction at 14 d. real-time quantitative reverse transcriptase polymerase chain reaction revealed improved collagen 1:collagen 3 (Col1:Col3) ratio in the medium-dose group and enhanced α-smooth muscle actin in the high-dose group at 14 d. Western blot demonstrated increased cluster of differentiation 31 protein at 2 wk in wounds receiving >106 cells/cm2. Doses up to 3.0 × 106 cells/cm2 were well-tolerated. High-dose ASCs accelerate wound contraction, enhance neovascularization, and may improve scar quality in excisional wounds healing by secondary intention. Doses greater than those previously used may be necessary to achieve desired effects.