Healing diabetes wounds with exosomal microRNA

Diabetes poses significant challenges to patients, with one of the most concerning complications being the development of refractory wounds. These wounds, often slow to heal and prone to infection, can lead to serious health complications. Researchers have long been investigating novel treatment approaches to accelerate wound healing in diabetic patients. Recently, a promising avenue of research has emerged involving the use of exosomes derived from bone marrow mesenchymal stem cells (BMSCs) under hypoxic conditions. These tiny vesicles hold immense potential for normalizing cellular processes implicated in diabetic wound healing, offering hope for more effective therapies.

Researchers at Nanchang University sought to explore the therapeutic potential of hypoxic BMSC-derived exosomes (hyBMSC-Exos) in diabetic wound healing. The researchers compared the effects of these exosomes to those derived from BMSCs in normoxic conditions (noBMSC-Exos). Through a series of experiments involving morphometric assessments, molecular analyses, and in vivo mouse models of diabetes, the researchers investigated the mechanisms underlying the therapeutic effects of hyBMSC-Exos.

Schematic representation of the therapeutic effect of hyBMSC-Exos on diabetic wounds

Schematic representation of the therapeutic effect of hyBMSC-Exos on diabetic wounds. The schematic graph shows that hyBMSC-Exos promotes wound healing by promoting keratinocyte autophagy. Specifically, hyBMSC-Exo-mediated transfer of miR-4645-5p inactivates MAPKAPK2-induced AKT-mTORC1 signaling in keratinocytes, leading to keratinocyte autophagy, proliferation and migration. BMSC bone marrow mesenchymal stem cell, hyBMSC-Exo hypoxic BMSC-sourced exosome, AKT AKT kinase group [AKT1 (AKT serine/threonine kinase 1), AKT2 and AKT3], mTORC1 mechanistic target of rapamycin kinase complex 1, RPS6KB1 ribosomal protein S6 kinase B1

The schematic graph shows that hyBMSC-Exos promotes wound healing by promoting keratinocyte autophagy. Specifically, hyBMSC-Exo-mediated transfer of miR-4645-5p inactivates MAPKAPK2-induced AKT-mTORC1 signaling in keratinocytes, leading to keratinocyte autophagy, proliferation and migration. BMSC bone marrow mesenchymal stem cell, hyBMSC-Exo hypoxic BMSC-sourced exosome, AKT AKT kinase group [AKT1 (AKT serine/threonine kinase 1), AKT2 and AKT3], mTORC1 mechanistic target of rapamycin kinase complex 1, RPS6KB1 ribosomal protein S6 kinase B1

The study revealed several important findings. Firstly, hypoxia influenced the release, size, and morphology of exosomes from BMSCs, suggesting a potential role of the hypoxic microenvironment in enhancing the therapeutic properties of these vesicles. Additionally, treatment with hyBMSC-Exos significantly improved keratinocyte function, including autophagy, proliferation, and migration, key processes involved in wound healing.

Further molecular analyses identified miR-4645-5p as a critical mediator of the pro-autophagy effects of hyBMSC-Exos. This microRNA was found to target MAPKAPK2, a protein involved in the AKT-mTORC1 signaling pathway. By inactivating MAPKAPK2-induced AKT-mTORC1 signaling, miR-4645-5p facilitated autophagy activation in keratinocytes, ultimately promoting diabetic wound healing in mice.

The findings of this study hold significant implications for the development of novel therapeutic strategies for diabetic wounds. By harnessing the regenerative potential of stem cell-derived exosomes and elucidating the underlying molecular mechanisms, researchers may pave the way for more effective treatments for diabetic patients suffering from chronic wounds. Moreover, this research highlights the importance of exploring innovative approaches that capitalize on the therapeutic properties of exosomes in regenerative medicine.

Dr. Yan Shi, the lead researcher, states, “Our findings offer a new horizon in diabetic wound care. By harnessing the power of stem cell-derived exosomes, particularly under hypoxic conditions, we’ve seen a remarkable improvement in wound healing processes, opening doors to potentially life-saving treatments.”

The study underscores the promising potential of hyBMSC-Exos as a therapeutic intervention for diabetic wound healing. By shedding light on the molecular mechanisms involved, the findings offer valuable insights into the development of targeted therapies aimed at addressing the unmet needs of diabetic patients with refractory wounds. Moving forward, further research in this area could lead to the translation of these findings into clinical practice, offering hope for improved outcomes and quality of life for individuals living with diabetes.

Shi Y, Wang S, Liu D, Wang Z, Zhu Y, Li J, Xu K, Li F, Wen H, Yang R. (2024) Exosomal miR-4645-5p from hypoxic bone marrow mesenchymal stem cells facilitates diabetic wound healing by restoring keratinocyte autophagy. Burns Trauma [Epub ahead of print]. [article]

Leave a Reply

Your email address will not be published. Required fields are marked *

*