Mesenchymal stem/stromal cells (MSCs) are central to the bone marrow microenvironment and have strong immunomodulatory and regenerative properties, making them attractive tools in hematology and blood cancers. At the same time, MSCs can also support malignant cells, so their therapeutic use in hemato-oncology must be carefully controlled.
MSCs support hematopoietic stem cells and are being used to improve engraftment and outcomes after HSCT in leukemias and other hematologic disorders (Lan et al., 2021; Smallbone et al., 2025). Their immunosuppressive effects are exploited to treat or prevent graft versus host disease (GVHD) and to repair damaged marrow after chemo radiotherapy (Wu et al., 2024; Lan et al., 2021; Najar et al., 2022; Smallbone et al., 2025).
MSCs and their exosomes can modulate leukemic microenvironments, induce cell cycle arrest, promote apoptosis and reduce chemoresistance in some leukemias, suggesting direct anti-leukemic potential and synergy with standard therapies (Saadh et al., 2025; Wu et al., 2024; Fathi et al., 2019; Ahmad et al., 2025). Gene-modified MSCs are being developed as “Trojan horses” to deliver cytokines, suicide genes, antibodies or coagulation factors in leukemias, lymphomas, myeloma and hereditary blood disorders such as anemia and hemophilia (Hmadcha et al., 2020; Shomali et al., 2020; Chulpanova et al., 2018; Kangari et al., 2024).
| Strategy | Therapeutic goal in hematology/hemato-oncology | Citations |
|---|---|---|
| Co-infused MSCs with HSCT | Enhance engraftment, reduce GVHD, repair niche | (Wu et al., 2024; Lan et al., 2021; Crippa et al., 2019; Najar et al., 2022; Smallbone et al., 2025) |
| MSC derived exosomes | Cell-free control of inflammation, chemoresistance, tumor growth | (Saadh et al., 2025; Ahmad et al., 2025; Lin et al., 2022) |
| MSCs as gene/drug carriers | Targeted delivery of anti-cancer genes, cytokines, factors in blood disorders | (Hmadcha et al., 2020; Shomali et al., 2020; Chulpanova et al., 2018) |
Figure 1: Main clinical and experimental MSC uses in hematology.
MSCs are powerful tools in hemato oncology: they support HSCT, modulate immunity, deliver therapeutic agents, and, via exosomes,offer promising cell free strategies.
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Saadh, M., Fard, N., Hussein, A., Mirzazadeh, A., Siavashi, M., SeyedMoharami, F., Noroozi, S., & Samarkhazan, H. (2025). Mesenchymal stem cells in the bone marrow microenvironment: a double-edged sword for AML. Journal of Cancer Research and Clinical Oncology, 151. https://doi.org/10.1007/s00432-025-06244-4
Wu, C., Weng, T., Li, J., & Wu, K. (2024). Biology and Therapeutic Properties of Mesenchymal Stem Cells in Leukemia. International Journal of Molecular Sciences, 25. https://doi.org/10.3390/ijms25052527
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Crippa, S., Santi, L., Bosotti, R., Porro, G., & Bernardo, M. (2019). Bone Marrow-Derived Mesenchymal Stromal Cells: A Novel Target to Optimize Hematopoietic Stem Cell Transplantation Protocols in Hematological Malignancies and Rare Genetic Disorders. Journal of Clinical Medicine, 9. https://doi.org/10.3390/jcm9010002
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(2023). Engagement of Mesenchymal Stromal Cells in the Remodeling of the Bone Marrow Microenvironment in Hematological Cancers. Biomolecules, 13. https://doi.org/10.3390/biom13121701
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