Adipose-Derived Mesenchymal Stem Cells in the Treatment of Diabetic Foot Ulcers: A Review of Preclinical and Clinical Studies

Abstract

This review provides an outline of the use of adipose-derived mesenchymal stem cells (AMSCs) in the treatment of diabetic foot ulcers (DFUs). A systematic search of PubMed and the Cochrane database was performed on October 2, 2019. Eighteen studies were identified (14 preclinical and 4 clinical). Studies in animal models have demonstrated that AMSCs enhance diabetic wound healing, accelerate granulation tissue formation, and increase reepithelialization and neovascularization. Only 1 randomized control trial has been published so far. Patients (n = 25) with DFUs were treated using an allogeneic AMSC directly on the wound bed as a primary dressing, and improvements were found in complete wound closure in the treatment group (n = 16). Three clinical studies showed that autologous AMSC might be a safe alternative to achieve therapeutic angiogenesis in patients with diabetes and peripheral arterial disease. Based on the available evidence, AMSCs hold promise in the treatment of DFUs. However, this evidence requires confirmation by well-designed trials. Additional studies are also required to understand some issues regarding this treatment for DFUs. For example, the potential application of autologous or allogeneic AMSCs in different types of DFUs, optimal dose/infusion schedules, safety evaluations, and cost-effectiveness.

Sodium alginate/gelatin hydrogels loaded with adipose‐derived mesenchymal stem cells promote wound healing in diabetic rats

“…Diabetic wound healing can be promoted by ASCs seeded in Pluronic F‐127 hydrogels 21 . ASCs promote granulation tissue formation and facilitate diabetic wound healing 24 . Furthermore, ASCs have been shown to improve wound healing through promoting collagen synthesis 25,26 .…”

Stem Cell-Based Therapy: A Promising Treatment for Diabetic Foot Ulcer

“…Since AMSCs are harvested from autologous adult fat, fewer ethical controversies exist [ 95 ]. In addition, several studies have shown that AMSCs are able to promote wound healing via increasing epithelization and granulation tissue formation, via their anti-inflammatory and anti-apoptotic effects, and through the release of angiogenic cytokines [ 96 , 97 ]. A study by Cianfarani et al reported that diabetes mellitus impairs the function of AMSCs and alters their intrinsic properties, which affects their healing properties in DFU in diabetic rat models [ 98 ].…”

“…Moreover, studies assessing wound healing have reported beneficial effects of adding platelet-rich plasma to AMSCs, specifically acting as a powerful paracrine effector and cell carrier to increase the potential of transplanted cells used in therapies [ 102 ]. In addition to diabetes, obesity and aging negatively impact AMSCs, impairing their function and properties including angiogenesis, multipotent state, differentiation, metabolism, and immunomodulation [ 95 , 97 , 103 , 104 , 105 ]. As a result, it can be deduced that employing allogeneic normal AMSCs rather than autologous, diabetic, and impaired ones is a better alternative in cell therapy to promote wound healing in diabetic patients [ 99 ].…”

Health-related quality of life outcomes and hospitalization length of stay after micro-fragmented autologous adipose tissue injection in minor amputations for diabetic foot ulceration (MiFrAADiF Trial): results from a randomized controlled single-center clinical trial

“…16 A larger multicenter trial would be required to confirm the present results. 30 The impact of the LOS reduction on the overall costs of care represents an additional point of interest for health care providers. Future investigations are required on this specific topic.…”