Mesenchymal stem cell-derived exosomes: a novel therapeutic frontier in hematological disorders

Mesenchymal stem cells (MSCs) are multipotent stromal cells valued for their immunomodulatory and regenerative properties, positioning them as a cornerstone of regenerative medicine. Their derived exosomes small extracellular vesicles laden with bioactive molecules such as proteins, lipids, and nucleic acids have emerged as critical mediators of MSC therapeutic effects. This review systematically explores the biology of MSC-derived exosomes, detailing their biogenesis, molecular composition, and pivotal roles in hematopoiesis, inflammation, and immune regulation. In hematological disorders, including leukemia, lymphoma, and myelodysplastic syndromes, these exosomes exhibit significant therapeutic potential by modulating the tumor microenvironment, enhancing hematopoietic recovery, and suppressing malignant cell proliferation. Notable findings include their ability to induce cell cycle arrest in leukemia cells via the p53 pathway and to reduce chemoresistance through targeted signaling mechanisms, such as the IRF2/INPP4B axis. However, clinical translation is hindered by several challenges, including the standardization of isolation techniques such as ultracentrifugation which are costly and susceptible to contamination as well as difficulties in optimizing large-scale production and ensuring long-term safety and efficacy. Despite these obstacles, MSC-derived exosomes offer a promising, cell-free therapeutic alternative that minimizes risks such as immune rejection and tumorigenicity associated with whole-cell therapies. Future research must prioritize the refinement of isolation and production protocols, the development of precise delivery strategies, and the execution of comprehensive safety evaluations to unlock their full clinical potential in treating hematological disorders and beyond. This review integrates recent advancements to provide a clearer understanding of their multifaceted contributions and highlights the critical gaps that remain.