Stem Cell-Based Therapeutic Strategies in Diabetic Wound Healing

Abstract

Impaired wound healing and especially the “all-too-common” occurrence of associated diabetic foot ulcers (DFU) are becoming an increasingly urgent and deteriorating healthcare issue, which drastically impact the quality of life and further heighten the risks of infection and amputation in patients with diabetes mellitus. Amongst the multifactorial wound healing determinants, glycemic dysregulation has been identified to be the primary casual factor of poor wound healing. Unfortunately, current therapeutic modalities merely serve as moderate symptomatic relieves but often fail to completely restore the wound site to its pre-injury state and prevent further recurrence. Stem cell-based therapeutics have been employed for its promising potential to address the root of the problem as they not only exhibit the capacity for self-renewal and differentiation towards multiple lineages, but also have been disclosed to participate in mediating variant growth factors and cytokines. Herein we review the current literatures on the therapeutic benefits of using various kinds of stem cells, including embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), mesenchymal stem cells (MSCs), and adipose-derived stem cells (ASCs) in diabetic wound healing by searching on the PubMed® Database for publications. This study shall serve as an overview of the current body of research with particular focus on autologous ASCs and the laboratory expandable iPSCs in hope of shedding more light on this attractive therapy so as to elevate the efficacy of wound healing that is almost always compromised in diabetic patients.

Mesenchymal Stem Cell Aggregation‐Released Extracellular Vesicles Induce CD31+EMCN+ Vessels in Skin Regeneration and Improve Diabetic Wound Healing

“…Stem cell-based therapies arise to exhibit enormous potential for promoting the regeneration of nonhealing wounds in both preclinical studies and clinical trials. [65][66][67] Of note, the key focus is on MSCs that can be easily isolated from various tissue sources and exert therapeutic activity by homing to injury sites and modulating the recipient environment. [68][69][70] However, the efficacy of MSCs is compromised by the common injection strategy, due to limited cell survival, retention and engraftment.…”

Nanofibrous Scaffolds for Diabetic Wound Healing

“…Adipose-derived stem cells (ASC) are readily available, possess similar physical and functional characteristics with BM-MSC, and promote diabetic wound healing by increasing tissue regeneration and angiogenesis. It was also reported that ACS promotes cell development by depositing growth factors, such as vascular endothelial growth factor and human growth factor when used topically [ 102 ]. Fu et al [ 103 ] noted the challenges associated with efficiently stabilizing MSC for topical administration due to the high level of proteolysis occurring at the delivery site and therefore engineered a scaffold based on reduced graphene oxide (RGO) nanoparticle combined with an acellular dermal matrix (ADM) that encapsulated MSC.…”

“…Another growth factor that is widely considered for chronic wound treatment is the vascular endothelial growth factor (VEGF) due to its vasculogenic and angiogenic activity. It stimulated cell proliferation, migration of fibroblasts, deposition of collagen, and re-epithelialization when administered through scaffolds in diabetic rats [ 102 ]. Vijayan and others [ 43 ] also reported on the construction of nano-encapsulated vascular endothelial growth factor and basic fibroblast growth factors adsorbed onto electrospun collagen/PLGA/chitosan-based scaffolding structures that aided angiogenesis, cell proliferation, collagen deposition, and re-epithelialization at the diabetic wound site.…”

IFN‐γ enhances the therapeutic efficacy of MSCs‐derived exosome via miR‐126‐3p in diabetic wound healing by targeting SPRED1

“…Therapies based on mesenchymal stem cells (MSCs) have recently attracted much interest 4 . However, worries about immune‐mediated rejection, potential malignant transformation, and limited activity of transplanted cells make the practical application of MSCs problematic 5 .…”

“…Therapies based on mesenchymal stem cells (MSCs) have recently attracted much interest. 4 However, worries about immune‐mediated rejection, potential malignant transformation, and limited activity of transplanted cells make the practical application of MSCs problematic. 5 Exosomes, which are extracellular vesicles with a diameter of 30–200 nm, are particles released by cells that carry bioactive molecules.…”