مقالات پذیرفته شده در نهمین کنگره بین المللی زیست پزشکی
Exosomes in Regenerative Medicine: A Cell-Free Therapeutic approach
Exosomes in Regenerative Medicine: A Cell-Free Therapeutic approach
Anahita Khorshidi,1Maryam Eslami,2,*
1. Department of Genetic, Faculty of Advanced Sciences and Technology, TeMS.C.,Islamic Azad University, Islamic Azad University, Tehran, Iran. 2. Department of Genetic, Faculty of Advanced Sciences and Technology, TeMS.C.,Islamic Azad University, Islamic Azad University, Tehran, Iran.
Introduction: Regenerative medicine is an emerging field aimed at repairing, replacing, or regenerating damaged tissues and organs. Stem cells play a pivotal role in regenerative strategies due to their self-renewal capacity and potential to differentiate into various specialized cell types. Among the different stem cell types, mesenchymal stem cells (MSCs) have emerged as the primary candidates for cell-based therapies. However, studies have demonstrated that many therapeutic effects of stem cells are mediated by their paracrine secretions rather than direct engraftment. Consequently, stem cell secretomes, which exhibit lower immunogenicity and minimal toxicity, have become an increasingly interesting focus in regenerative medicine. Exosomes, a subset of extracellular vesicles (EVs), have received the most attention in this context. These nanoscale vesicles (30–150 nm) carry proteins, lipids, and functional RNAs, playing a crucial role in intercellular communication. Due to their biocompatibility, exosomes elicit minimal immune response, making them a safer and increasingly effective alternative to direct cell therapy.
Methods: This narrative review was conducted by searching international databases including PubMed, Scopus, and Web of Science up to 2025. Keywords used included "Mesenchymal Stem Cells," "Exosomes," "Regenerative Medicine," and "Clinical Application." Selected articles encompassed basic science studies, preclinical animal models, early-phase clinical trials, and structured reviews related to the applications of MSC-derived exosomes and exosome-loaded scaffolds in tissue regeneration.
Results: 1. Wound Healing: Exosomes derived from MSCs of adipose tissue, bone marrow, and umbilical cord can modulate inflammatory responses, promote re-epithelialization, inhibit apoptosis via AKT signaling, enhance angiogenesis, and facilitate collagen remodeling through the transfer of regulatory miRNAs. These mechanisms accelerate the resolution of chronic inflammation that impedes healing, including in conditions such as diabetes. While exosomes can be directly applied to injured sites, their stability and controlled release are enhanced when delivered via hydrogel-based scaffolds.
2. Neural Tissue Repair and Brain Injury: Traumatic brain injury (TBI) triggers acute brain trauma followed by a pro-inflammatory immune response. If uncontrolled, this can lead to chronic inflammation. Exosomes can cross the blood–brain barrier via intravenous or intranasal administration and deliver neuroprotective factors and miRNAs. Their anti-inflammatory properties make them promising candidates for the treatment of complex brain injuries. Additionally, exosomes are being investigated as potential biomarkers for stroke severity and type .
3. Bone Defect Regeneration: MSC-based bone tissue engineering, despite its successes, faces limitations such as phenotypic changes during culture, low cell survival, and limited engraftment. Exosome-based cell-free strategies have therefore emerged as effective alternatives. MSC- or osteoblast-derived exosomes can regulate gene expression via specific miRNAs, promoting osteogenic differentiation, enhancing angiogenesis, stimulating osteoblast proliferation, and supporting cartilage regeneration by modulating macrophage polarization and anti-apoptotic activity.
4. Cardiovascular Disease: Exosomes play significant roles in cardiovascular physiology. Compared with cell therapy, they present lower immunogenicity, minimal embolic risk, and high biocompatibility. In myocardial infarction, exosomes can reduce acute cardiac injury by suppressing local inflammatory responses via downregulation of pro-inflammatory cytokines (IL-6, IL-1β, TNF-α) and by increasing miR-let7 expression, which provides protective effects against atherosclerosis progression.
5. Liver Injury and Kidney Disease: Exosomes contribute to metabolic regulation, immune modulation, fibrosis attenuation, and hepatocellular carcinoma pathogenesis by affecting hepatocytes, Kupffer cells, and hepatic stellate cells. Additionally, they reduce oxidative stress and improve tissue microenvironments, facilitating regeneration of liver and kidney tissues.
6. Challenges and Limitations: Although exosomes are more biocompatible, less toxic, and safer than stem cells, limitations include low stability, lack of standardized isolation and purification methods, high heterogeneity in cargo, and uncertainties regarding immune responses.
7. Optimizing Exosome-Based Therapies: The use of biodegradable scaffolds, such as polysaccharide-based hydrogels, nanofibers, or engineered biomaterials, as carriers for exosomes enables their gradual and targeted release, thereby enhancing the efficacy of regenerative therapies. Additionally, genetically modifying mesenchymal stem cells to produce exosomes enriched with specific miRNAs offers a promising strategy to advance clinical use of this technology.
Conclusion: MSC-derived exosomes represent a safe and efficient alternative to traditional cell therapy by modulating immune responses, promoting tissue regeneration, and improving organ function. Nevertheless, widespread clinical application requires further research on stability, controlled release, immune response, dose optimization, standardized production protocols, and large-scale human clinical trials. Advanced techniques, including hydrogel-based scaffolds for exosome delivery, pave the way for broader implementation of exosome therapies in regenerative medicine.