Development of a porcine delayed wound-healing model and its use in testing a novel cell-based therapy.
OBJECTIVE
A delayed full-thickness wound-healing model was developed and used for examining the capacity of adipose-derived stem cells (ASCs), either alone or in platelet-rich fibrin gels, to promote healing.


METHODS
Four pigs received electron beam radiation to the dorsal skin surface. Five weeks after radiation, subcutaneous fat was harvested from nonirradiated areas and processed to yield ASCs. Two weeks later, 28 to 30 full-thickness 1.5-cm(2) wounds were made in irradiated and nonirradiated skin. Wounds were treated with either saline solution, ASCs in saline solution, platelet-rich plasma (PRP) fibrin gel, ASCs in PRP, or non-autologous green fluorescence protein-labeled ASCs.


RESULTS
The single radiation dose produced a significant loss of dermal microvasculature density (75%) by 7 weeks. There was a significant difference in the rate of healing between irradiated and nonirradiated skin treated with saline solution. The ASCs in PRP-treated wounds exhibited a significant 11.2% improvement in wound healing compared with saline solution. Enhancement was dependent on the combination of ASCs and PRP, because neither ASCs nor PRP alone had an effect.


CONCLUSIONS
We have created a model that simulates the clinically relevant late radiation effects of delayed wound healing. Using this model, we showed that a combination of ASCs and PRP improves the healing rates of perfusion-depleted tissues, possibly through enhancing local levels of growth factors.
Hadad
Ivan
I
Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA. ihadad@iupui.edu
Johnstone
Brian H
BH
Brabham
Jeffrey G
JG
Blanton
Matthew W
MW
Rogers
Pamela I
PI
Fellers
Cory
C
Solomon
James L
JL
Merfeld-Clauss
Stephanie
S
DesRosiers
Colleen M
CM
Dynlacht
Joseph R
JR
Coleman
John J
JJ
March
Keith L
KL
D017667:Adipocytes / Q000166:cytology / Q000502:physiology / Q000637:transplantation*; D000818:Animals; D003286:Contracture / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005337:Fibrin / Q000627:therapeutic use; D055806:Microvessels / Q000473:pathology / Q000528:radiation effects; D023421:Models, Animal; D053657:Platelet-Rich Plasma; D011833:Radiation Injuries, Experimental / Q000473:pathology / Q000628:therapy*; D011855:Radiodermatitis / Q000473:pathology / Q000628:therapy; D012867:Skin / Q000098:blood supply / Q000293:injuries* / Q000528:radiation effects; D012965:Sodium Chloride / Q000627:therapeutic use; D033581:Stem Cell Transplantation; D013552:Swine; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects
D012965:Sodium Chloride; D005337:Fibrin