مقالات پذیرفته شده در نهمین کنگره بین المللی زیست پزشکی
Harnessing Stem Cell-Derived Exosomes as Advanced Delivery Systems for microRNA-Based Therapy in Diabetic Wound Healing
Harnessing Stem Cell-Derived Exosomes as Advanced Delivery Systems for microRNA-Based Therapy in Diabetic Wound Healing
Mahdieh SobhZahedi,1Mohammad Hossein YektaKooshali,2,*
1. Ph.D. Student in Genetics, Department of Biology, Faculty of Science, University of Guilan, Rasht, Iran. 2. Ph.D. Student in Applied Cell Sciences, Department of Applied Cell Sciences and Tissue Engineering, School of Paramedicine, Guilan University of Medical Sciences, Rasht, Iran.
Introduction: Diabetic wound healing is a multifaceted process often disrupted by persistent inflammation, impaired angiogenesis, and aberrant tissue remodeling. MicroRNAs (miRNAs) have surfaced as key regulators of these pathways, but their therapeutic application is limited by issues of stability and targeted delivery. This review explores the transformative potential of stem cell-derived exosomes as natural nanocarriers for delivering miRNAs to diabetic wounds. These extracellular vesicles (30–150 nm) offer distinct advantages, including low immunogenicity, excellent biocompatibility, protection of nucleic acid payloads, and efficient cellular uptake, making them promising vehicles for regenerative medicine.
Methods: A comprehensive literature review was conducted using PubMed, Scopus, Web of Science, and Embase to identify relevant studies published from 2010 to 2025. Search terms included combinations of “exosomes,” “microRNA,” “diabetic wound healing,” “mesenchymal stem cells,” and “regenerative medicine.” Only peer-reviewed articles focusing on exosome-mediated miRNA delivery in preclinical or clinical settings were included, with a preference for studies involving mesenchymal stem cell (MSC)-derived exosomes.
Results: Analysis of 52 studies revealed that MSC-derived exosomes, sourced from bone marrow, umbilical cord, or adipose tissue, are highly effective due to their pluripotent properties and robust paracrine signaling. These studies demonstrated that exosomes loaded with miR-223 and miR-let-7b promote a shift to anti-inflammatory M2 macrophages, mitigating chronic inflammation. During the proliferative phase, miR-17-92, miR-182-5p, and miR-21-5p delivered via exosomes enhance angiogenesis by activating VEGF receptor pathways and reducing endothelial cell ferroptosis. Furthermore, exosomal miR-21, miR-23a, and miR-145 suppress the TGF-β/SMAD2 pathway, limiting myofibroblast activity and fibrotic scarring to improve tissue repair quality. Despite these advances, challenges such as inconsistent exosome characterization, variable miRNA loading efficiency, and scalable production were frequently noted, underscoring gaps in current research.
Conclusion: This review highlights the remarkable potential of MSC-derived exosomes as miRNA delivery platforms for diabetic wound healing, offering targeted modulation of inflammation, angiogenesis, and tissue remodeling. However, hurdles in large-scale production, standardization, and long-term safety evaluation persist. Future efforts should focus on refining manufacturing processes, improving delivery precision, and conducting rigorous in vivo studies to pave the way for clinical translation of this innovative therapy.