Treatment of diabetic wounds with fetal murine mesenchymal stromal cells enhances wound closure.
Diabetes impairs multiple aspects of the wound-healing response. Delayed wound healing continues to be a significant healthcare problem for which effective therapies are lacking. We have hypothesized that local delivery of mesenchymal stromal cells (MSC) at a wound might correct many of the wound-healing impairments seen in diabetic lesions. We treated excisional wounds of genetically diabetic (Db-/Db-) mice and heterozygous controls with either MSC, CD45(+) cells, or vehicle. At 7 days, treatment with MSC resulted in a decrease in the epithelial gap from 3.2 +/- 0.5 mm in vehicle-treated wounds to 1.3 +/- 0.4 mm in MSC-treated wounds and an increase in granulation tissue from 0.8 +/- 0.3 mm(2) to 2.4 +/- 0.6 mm(2), respectively (mean +/- SD, P < 0.04). MSC-treated wounds also displayed a higher density of CD31(+) vessels and exhibited increases in the production of mRNA for epidermal growth factor, transforming growth factor beta 1, vascular endothelial growth factor, and stromal-derived growth factor 1-alpha. MSC also demonstrated greater contractile ability than fibroblast controls in a collagen gel contraction assay. The effects of locally applied MSC are thus sufficient to improve healing in diabetic mice. Possible mechanisms of this effect include augmented local growth-factor production, improved neovascularization, enhanced cellular recruitment to wounds, and improved wound contraction.
Badillo
Andrea T
AT
The Center for Fetal Research at The Children's Hospital of Philadelphia, The University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Redden
Robert A
RA
Zhang
Liping
L
Doolin
Edward J
EJ
Liechty
Kenneth W
KW
D000818:Animals; D002454:Cell Differentiation; D003094:Collagen / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis; D048909:Diabetes Complications / Q000473:pathology / Q000628:therapy*; D004848:Epithelium / Q000473:pathology; D005109:Extracellular Matrix / Q000502:physiology; D005260:Female; D005333:Fetus / Q000166:cytology; D005782:Gels; D006097:Granulation Tissue / Q000473:pathology; D049452:Green Fluorescent Proteins / Q000096:biosynthesis; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology*; D051379:Mice; D008822:Mice, Transgenic; D012867:Skin / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D017154:Stromal Cells / Q000502:physiology / Q000637:transplantation*; D014945:Wound Healing
D016207:Cytokines; D005782:Gels; D036341:Intercellular Signaling Peptides and Proteins; D049452:Green Fluorescent Proteins; D003094:Collagen