Enhanced Healing of Diabetic Wounds by Subcutaneous Administration of Human Umbilical Cord Derived Stem Cells and Their Conditioned Media

Abstract

Objective. Mesenchymal stem cells (MSCs) isolated from the umbilical cord and their conditioned media (CM) can be easily obtained and refined compared with stem cells from other sources. Here, we explore the possibility of the benefits of these cells in healing diabetic wounds. Methodology and Results. Delayed wound healing animal models were established by making a standard wound on the dorsum of eighteen db/db mice, which were divided into three groups with six mice in each: groups I, II, and III received PBS, UC-MSC, and CM, respectively. UC-MSC and their CM significantly accelerated wound closure compared to PBS-treated wounds, and it was most rapid in CM-injected wounds. In day-14 wounds, significant difference in capillary densities among the three groups was noted (n = 6; P < 0.05), and higher levels of VEGF, PDGF, and KGF expression in the CM- and UC-MSC-injected wounds compared to the PBS-treated wounds were seen. The expression levels of PDGF-β and KGF were higher in CM-treated wounds than those in UC-MSC-treated wounds. Conclusion. Both the transplantation of UC-MSC and their CM are beneficial to diabetic wound healing, and CM has been shown to be therapeutically better than UC-MSC, at least in the context of diabetic wound healing.

Mesenchymal Stem Cell Therapy in Type 1 Diabetes Mellitus and Its Main Complications: From Experimental Findings to Clinical Practice

“…Wounds treated with MSCs in these reports have shown a qualitative improvement regarding histological characteristics, such as superior rete ridge architecture, multi-layered structure, improved dermalepidermal junction and the formation of new skin appendage structures, such as hair follicles and sebaceous glands [120][121][122][123].…”

“…MSCs have been used to date in treating different skin disorders [20,118,119]; several groups have reported successful wound healing in pre-clinical models of diabetic wounds after the administration of autologous or allogeneic MSCs from different sources [120][121][122][123]. Wounds treated with MSCs in these reports have shown a qualitative improvement regarding histological characteristics, such as superior rete ridge architecture, multi-layered structure, improved dermalepidermal junction and the formation of new skin appendage structures, such as hair follicles and sebaceous glands [120][121][122][123].…”

“…On the other hand, other studies have revealed that transplanted MSCs do not necessarily have to be in close proximity to damaged tissue to promote wound repair and functional recovery, thereby suggesting that paracrine factor secretion is the main MSC therapeutic action concerned in repairing skin disorders [129,130]. This theory has been further reinforced by recent studies which have shown that allogeneic MSCs-conditioned medium has enhanced healing when administered locally into wounds [121,122,[131][132][133][134].…”

Stem Cell and Stem Cell-Derived Molecular Therapies to Enhance Dermal Wound Healing

“…Similarly, human Wharton's jelly-derived MSC-conditioned media increased the rate of wound closure in mice when delivered in a Matrigel hydrogel, compared to Matrigel alone [ 80 ]. Shrestha et al demonstrated that repeated subcutaneous injection of umbilical cord-derived MSC-conditioned media improved wound healing compared to a single injection of umbilical cord-derived MSCs, suggesting that strategies for sustained delivery of stem cell-conditioned media would be benefi cial in wound therapies [ 110 ].…”

Elastin-based biomaterials and mesenchymal stem cells

“…Experiments and clinical trials have highlighted the beneficial effects of MSCs from a variety of sources in dermal repair 133–136 . Several studies have recognized the importance of delivering MSCs through a scaffold.…”