Topical lineage-negative progenitor-cell therapy for diabetic wounds.
BACKGROUND
Impaired diabetic wound healing is due, in part, to defects in mesenchymal progenitor cell tracking. Theoretically, these defects may be overcome by administering purified progenitor cells directly to the diabetic wound. The authors hypothesize that these progenitor cells will differentiate into endothelial cells, increase wound vascularity, and improve wound healing.


METHODS
Lineage-negative progenitor cells were isolated from wild-type murine bone marrow by magnetic cell sorting, suspended in a collagen matrix, and applied topically to full-thickness excisional dorsal cutaneous wounds in diabetic mice. Application of lineage-positive hematopoietic cells or acellular collagen matrix served as comparative controls (n = 16 for each group; n = 48 total). Time to closure and percentage closure were calculated by morphometry. Wounds were harvested at 7, 14, 21, and 28 days and then processed, sectioned, stained (lectin/DiI and CD31), and vascularity was quantified.


RESULTS
: Wounds treated with lineage-negative cells demonstrated a significantly decreased time to closure (14 days) compared with lineage-positive (21 days, p = 0.013) and collagen controls (28 days, p = 0.004), and a significant improvement in percentage closure at 14 days compared with the lineage-positive group (p < 0.01) and the collagen control (p < 0.01). Fluorescently tagged lineage-negative cells remained viable in the wound for 28 days, whereas lineage-positive cells were not present after 7 days. Lineage-negative, but not lineage-positive, cells differentiated into endothelial cells. Vascular density and vessel cross-sectional area were significantly higher in lineage-negative wounds.


CONCLUSIONS
Topical progenitor-cell therapy successfully accelerates diabetic wound closure and improves wound vascularity.
Lin
Clarence D
CD
New York, N.Y. From the Institute of Reconstructive Plastic Surgery Laboratories, New York University Medical Center.
Allori
Alexander C
AC
Macklin
Jared E
JE
Sailon
Alexander M
AM
Tanaka
Rica
R
Levine
Jamie P
JP
Saadeh
Pierre B
PB
Warren
Stephen M
SM
D000818:Animals; D001808:Blood Vessels / Q000166:cytology; D002454:Cell Differentiation; D019070:Cell Lineage; D048909:Diabetes Complications / Q000628:therapy*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D018189:Immunomagnetic Separation; D015552:Injections, Intralesional; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D054411:Receptors, Leptin / Q000235:genetics; D012867:Skin / Q000098:blood supply; D012883:Skin Ulcer / Q000628:therapy*; D014945:Wound Healing
D054411:Receptors, Leptin