Obesity impairs wound closure through a vasculogenic mechanism.
Since obesity impairs wound healing and bone marrow (BM)-derived vasculogenic progenitor cells (PCs) are important for tissue repair, we hypothesize that obesity-impaired wound healing is due, in part, to impaired PC mobilization, trafficking, and function. Peripheral blood was obtained from nondiabetic, obese (BMI > 30, n = 25), and nonobese (BMI < 30, n = 17) subjects. Peripheral blood human (h)PCs were isolated, quantified, and functionally assessed. To corroborate the human experiments, 6-mm stented wounds were created on nondiabetic obese mice (TALLYHO/JngJ, n = 15) and nonobese mice (SWR/J, n = 15). Peripheral blood mouse (m)PCs were quantified and wounds were analyzed. There was no difference in the number of baseline circulating hPCs in nondiabetic, obese (hPC-ob), and nonobese (hPC-nl) subjects, but hPC-ob had impaired adhesion (p < 0.05), migration (p < 0.01), and proliferation (p < 0.001). Nondiabetic obese mice had a significant decrease in the number of circulating PCs (mPC-ob) at 7 (p = 0.008) and 14 days (p = 0.003) after wounding. The impaired circulating mPC-ob response correlated with significantly impaired wound closure at days 14 (p < 0.001) and 21 (p < 0.001) as well as significantly fewer new blood vessels in the wounds (p < 0.001). Our results suggest that obesity impairs the BM-derived vasculogenic PC response to peripheral injury and this, in turn, impairs wound closure.
Department of Surgery, Temple School of Medicine, Temple University Hospital, Philadelphia, Pennsylvania, USA.
I Janelle
IJ
Wagner
Caroline
C
Szpalski
Robert J
RJ
Allen
Edward H
EH
Davidson
Orlando
O
Canizares
Pierre B
PB
Saadeh
Stephen M
SM
Warren
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D002448:Cell Adhesion; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008820:Mice, Obese; D008875:Middle Aged; D018919:Neovascularization, Physiologic; D009765:Obesity / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology; D020858:Tissue and Organ Harvesting; D014945:Wound Healing; D014947:Wounds and Injuries / Q000473:pathology / Q000503:physiopathology*; D055815:Young Adult