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A Porcine Model for Studying Stem Cell Therapy in Wound Healing
Isaac James, Debra Bourne, Nataliya Kostereva, Jenny Lei, Peng Chang, Kacey Marra, J. Peter Rubin
University of Pittsburgh Medical Center, Department of Plastic Surgery
2015-03-15
Presenter: Isaac James
Affidavit:
This represents original work by the authors and has not been previously presented at any national meetings or previously published.
Director Name: Joseph Losee
Author Category: Medical Student
Presentation Category: Basic Science Research
Abstract Category: General Reconstruction
BACKGROUND
Adipose-derived stem cells (ASCs) are multipotent stem cells capable of replacing multiple tissue types and are ideal candidates for regenerative cell-based therapy. However, large animal models and dose-related effects have not been well studied. We sought to establish a reliable porcine model for wound healing and to optimize ASC dosing.
METHODS
Circular, full thickness excisional wounds 4cm in diameter (n=40) were created on the backs of 6 month old female Yorkshire pigs. Passage 1-3 porcine ASCs were fluorescently labeled with PKH26 and injected intraoperatively into the wound bed and around the wound perimeter at high (3.0*10^6 cells/cm^2; n=8), medium (1.0*10^6 cells/cm^2; n=8), and low (0.3*10^6 cells/cm^2; n=8) doses. Controls received either saline (n=8) or no treatment (n=8). Dressings were changed twice weekly. Epithelialization and contraction were quantified. Animals were sacrificed at 1 and 2 weeks postoperative, and wounds were collected for ASC tracking.
RESULTS
PKH26-labeled ASCs were abundant in treated wounds and fully integrated into the native tissue architecture by 1 week in a dose-dependent fashion. Full epithelialization was achieved in most wounds by day 14. Wounds receiving high dose ASCs trended toward greater percent contraction at days 10 (48.0% vs 37.9%) and 14 (65.5% vs 48.9%) postoperative compared to control.
CONCLUSIONS
Our porcine model is highly promising and well suited to assess stem cell-based therapies. ASC doses as high as 3.0*10^6 cells/cm^2 are well-tolerated when injected into incisional wounds and integrate into native tissue architecture by 1 week. At high doses, they may also mediate enhanced wound contraction.
