Mesenchymal stem cell-derived exosomes: The dawn of diabetic wound healing

Abstract

Chronic wound healing has long been an unmet medical need in the field of wound repair, with diabetes being one of the major etiologies. Diabetic chronic wounds (DCWs), especially diabetic foot ulcers, are one of the most threatening chronic complications of diabetes. Although the treatment strategies, drugs, and dressings for DCWs have made great progress, they remain ineffective in some patients with refractory wounds. Stem cell-based therapies have achieved specific efficacy in various fields, with mesenchymal stem cells (MSCs) being the most widely used. Although MSCs have achieved good feedback in preclinical studies and clinical trials in the treatment of cutaneous wounds or other situations, the potential safety concerns associated with allogeneic/autologous stem cells and unknown long-term health effects need further attention and supervision. Recent studies have reported that stem cells mainly exert their trauma repair effects through paracrine secretion, and exosomes play an important role in intercellular communication as their main bioactive component. MSC-derived exosomes (MSC-Exos) inherit the powerful inflammation and immune modulation, angiogenesis, cell proliferation and migration promotion, oxidative stress alleviation, collagen remodeling imbalances regulation of their parental cells, and can avoid the potential risks of direct stem cell transplantation to a large extent, thus demonstrating promising performance as novel "cell-free" therapies in chronic wounds. This review aimed to elucidate the potential mechanism and update the progress of MSC-Exos in DCW healing, thereby providing new therapeutic directions for DCWs that are difficult to be cured using conventional therapy.

A clinical study of the local injection of a freshly manufactured 35 kDa hyaluronan fragment for treating chronic wounds

“…This study hypothesised that injection of the tissue-permeable 35 kDa hyaluronan fragment HA35 into healthy skin immediately surrounding chronic wounds has therapeutic effects on alleviating chronic wound-related pain and enhancing chronic wound healing. 34,35 In this study, 20 patients with chronic wounds accompanied by pain were treated by injecting freshly manufactured tissue-permeable HA fragment HA35 into the tissue under healthy skin immediately surrounding the chronic wounds. The results indicated that the injection of HA35 relieved the pain associated with chronic wounds within 24 hours (Figure 2), suggesting HA35 can reduce the inflammatory pain caused by chronic wounds.…”

“…Caires et al in Nature Communications reported that HMWHA reduced TRPV1 channel opening, 33 reducing peripheral nociceptor activity and pain, supporting the pain‐relieving effect of HA35. This study hypothesised that injection of the tissue‐permeable 35 kDa hyaluronan fragment HA35 into healthy skin immediately surrounding chronic wounds has therapeutic effects on alleviating chronic wound‐related pain and enhancing chronic wound healing 34,35 …”

“…This study hypothesised that injection of the tissue‐permeable 35 kDa hyaluronan fragment HA35 into healthy skin immediately surrounding chronic wounds has therapeutic effects on alleviating chronic wound‐related pain and enhancing chronic wound healing. 34 , 35 …”

Advancements and Insights in Exosome-Based Therapies for Wound Healing: A Comprehensive Systematic Review (2018–June 2023)

“…Exclusion criteria were applied to filter out the studies that did not meet the research goals, such as: (1) in vitro studies, (2) review articles, (3) non-English-language publication, (4) studies unrelated to wound healing, (5) no full access to the publication, and ( 6) studies not involving exosomes.…”

Obesity and Wound Healing: Focus on Mesenchymal Stem Cells

“…However, the use of ADSCs for the treatment of obesity-related disorders could not be limited to chronic wounds. In fact, ADSC-derived exosomes have been shown to inhibit both adipogenic differentiation and lipogenesis in ADSCs through activation of the Hedgehog (Hh) pathway [ 165 , 166 ]. Despite the promising results achieved with MSCs in the treatment of diabetes and its associated comorbidities, clinical data on the efficacy of autologous ADSCs are still lacking [ 167 , 168 ].…”