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.

Poly-ADP-ribose polymerase inhibition enhances ischemic and diabetic wound healing by promoting angiogenesis

“…Although multiple studies have shown a beneficial effect of injecting CD34 þ human cells directly into diabetic wounds in mice, [28][29][30] multiple clinical trials of this cellbased therapeutic angiogenesis for wound healing showed only limited clinical benefit. [31][32][33] For this cell-based therapy to be successful, the endothelial cells must attach to the extracellular matrix in the wound bed, migrate on the matrix, invade the matrix, form tube structures with polarized cells and tight cell junctions, and proliferate.…”

Treatment of Full-Thickness Skin Wounds with Blood-Derived CD34+ Precursor Cells Enhances Healing with Hair Follicle Regeneration

“…A previous study found that peripheral blood cd T lymphocytes in humans produce Fgf9 protein. 17 However, BDPCs or eBDPCs are not lymphocytes, confirmed by negative expression of surface markers for lymphocytes, such as CD3, CD4, CD8a, CD45, and lin. The further data also showed that BDPCs did not express TCR protein, which is a specific marker for cd T lymphocytes.…”

“…For example, CD34-enriched blood mononuclear cells injected into the ischemic limbs of diabetic mice showed a significant improvement in blood flow and rapid wound healing. 16,17 However, whether blood-derived CD34 + precursor cells can induce HFN and enhance local tissue regeneration has not been reported. We sought to address this question by purifying and expanding bloodderived CD34 + precursor cells (BDPCs), transplanting, and tracking their fate in the wounds.…”

Stem cell transplantation therapy for diabetic foot ulcer: a narrative review

“…Unlike vehicle-treated control models, animal models of injury receiving CD34 + had reduced levels of matrix metalloproteinase (MMPs), including MMP1, MMP3, MMP9, and MMP13, in their wound beds [ 14 ]. In a study by Chotinantakul et al [ 78 ], the use of expanded cord blood CD34 + cells or freshly isolated cord blood CD34 + cells accelerated wound repair through the successful deployment of macrophages and capillaries and re-epithelialization around the wound bed area. As presented in Table 1 , hematopoietic stem cells enhance wound healing, reduce ulcers, and enhance the blood supply in the lower extremities of diabetic patients.…”