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Enhancement of wound closure in diabetic mice by ex vivo expanded cord blood CD34+ cells

Abstract

Diabetes can impair wound closure, which can give rise to major clinical problems. Most treatments for wound repair in diabetes remain ineffective. This study aimed to investigate the influence on wound closure of treatments using expanded human cord blood CD34+ cells (CB-CD34+ cells), freshly isolated CB-CD34+ cells and a cytokine cocktail. The test subjects were mice with streptozotocin-induced diabetes. Wounds treated with fresh CB-CD34+ cells showed more rapid repair than mice given the PBS control. Injection of expanded CB-CD34+ cells improved wound closure significantly, whereas the injection of the cytokine cocktail alone did not improve wound repair. The results also demonstrated a significant decrease in epithelial gaps and advanced re-epithelialization over the wound bed area after treatment with either expanded CB-CD34+ cells or freshly isolated cells compared with the control. In addition, treatments with both CB-CD34+ cells and the cytokine cocktail were shown to promote recruitment of CD31+-endothelial cells in the wounds. Both the CB-CD34+ cell population and the cytokine treatments also enhanced the recruitment of CD68-positive cells in the early stages (day 3) of treatment compared with PBS control, although the degree of this enhancement was found to decline in the later stages (day 9). These results demonstrated that expanded CB-CD34+ cells or freshly isolated CB-CD34+ cells could accelerate wound repair by increasing the recruitment of macrophages and capillaries and the reepithelialization over the wound bed area. Our data suggest an effective role in wound closure for both ex vivo expanded CB-CD34+ cells and freshly isolated cells, and these may serve as therapeutic options for wound treatment for diabetic patients. Wound closure acceleration by expanded CB-CD34+ cells also breaks the insufficient quantity obstacle of stem cells per unit of cord blood and other stem cell sources, which indicates a broader potential for autologous transplantation.

Abbreviations

CB:

cord blood

DAPI:

4′,6-diamidino-2-phenylindole

Flt3-L:

Flt-3 ligand

HSC:

hematopoietic stem cell

IGF:

insulin-like growth factor

IL:

interleukin

MSC:

mesenchymal stem cell

PB:

peripheral blood

PDGF:

plateletderived growth factor

SCF:

stem cell factor

STZ:

streptozotocin

TGF-β:

transforming growth factor-β

TPO:

thrombopoietin

VEGF:

vascular endothelial growth factor

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Chotinantakul, K., Dechsukhum, C., Dejjuy, D. et al. Enhancement of wound closure in diabetic mice by ex vivo expanded cord blood CD34+ cells. Cell Mol Biol Lett 18, 263–283 (2013). https://doi.org/10.2478/s11658-013-0089-9

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  • DOI: https://doi.org/10.2478/s11658-013-0089-9

Key words

  • CD31+ cells
  • CD34+ cells
  • CD68+ cells
  • Cord blood
  • Diabetic mice
  • Ex vivo expansion
  • Hematopoietic stem cells
  • Macrophages
  • Stem cell therapy
  • Wound closure