Application of the chemokine CXCL12 expression plasmid restores wound healing to near normal in a diabetic mouse model.
BACKGROUND
CXCL12 is a chemokine involved in postinjury leukocyte chemotaxis, migration, and homing of stem cells. We hypothesized that by increasing the level of the chemokine CXCL12 in wounds of diabetic mice, we would increase stem cell recruitment to the wound and, thus, accelerate time to wound closure.


METHODS
Eighteen Lepr db-/db- (B6.Cg-m +/+ Leprdb/J; Jackson Labs, Bar Harbor, ME) and their nondiabetic littermates were wounded and treated either with an empty plasmid or a plasmid containing the CXCL12 gene. Wounds were measured approximately every 5 days until they closed completely and were analyzed using planimetry. Wounds were harvested, and relative expression of CXCL12 mRNA was measured using an ABI Prism SDS 7000. To study stem cells affected by this, the plasmid's affect on stem cell recruitment, we used flow cytometry.


RESULTS
The diabetic wounds contain a significantly decreased level of CXCL12 mRNA at day 7 postwounding, and these wounds take 55 days to heal. Application of a CXCL12 plasmid to diabetic wounds significantly increases CXCL12 mRNA at day 7, and these wounds heal in 23 days.


CONCLUSIONS
Lack of CXCL12 in diabetic wounds contributes to delayed wound healing and can be reversed via single application of a CXCL12-containing plasmid.
Restivo
Terry E
TE
Department of Surgery, University of California San Francisco-East Bay, Oakland, California, USA.
Mace
Kimberly A
KA
Harken
Alden H
AH
Young
David M
DM
D000818:Animals; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D048909:Diabetes Complications / Q000628:therapy*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D015316:Genetic Therapy / Q000379:methods*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010957:Plasmids / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D011897:Random Allocation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014945:Wound Healing / Q000235:genetics*
D054377:Chemokine CXCL12; D012333:RNA, Messenger