Baqiyatallah University of Medical Sciences International Journal of Medical Reviews 2345-525X 12 4 2025 12 01 The Therapeutic Potential of Stem Cells in Leukemia: Mechanisms and Clinical Directions 1012 1039 240570 10.30491/ijmr.2025.555989.1353 EN Leila Sadat Nilchiani Department of Molecular and Cell Biology, Faculty of Advanced Sciences and Technology, Islamic Azad University Tehran Medical Sciences, Tehran, Iran Raheleh Halabian Applied Microbiology Research Center, Biomedicine Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran Journal Article 2025 10 28 Leukemia remains a significant clinical challenge despite advances in chemotherapy, targeted therapies. Stem cell–based therapies represent a cornerstone in the treatment of leukemia, offering the potential for both curative and regenerative outcomes. Hematopoietic stem cell transplantation (HSCT) remains the most effective and widely used therapeutic approach, capable of restoring normal hematopoiesis following intensive chemotherapy or radiotherapy. Recent advances in stem cell biology and genetic engineering have further expanded the landscape of leukemia treatment. Induced pluripotent stem cells (iPSCs) and mesenchymal stem cells (MSCs) are being explored for their roles in disease modeling, drug screening, and as supportive agents to enhance engraftment and reduce transplant-related complications. This review provides a comprehensive overview of leukemia and its current therapeutic approaches, and examines the role of stem cells in modulating malignant hematopoiesis. Evidence from preclinical and clinical studies demonstrates that stem cells, particularly MSCs, hematopoietic stem cells (HSCs), and umbilical cord–derived or Wharton’s jelly–derived stem cells, can exert anti-leukemic effects through mechanisms such as apoptosis induction, cell cycle arrest, and modulation of the bone marrow microenvironment. The therapeutic potential of stem cells is explored in the context of major leukemia subtypes, acute myeloid leukemia (AML), acut e lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), and chronic lymphocytic leukemia (CLL), highlighting both in vitro and in vivo findings, including clinical trial evidence. Furthermore, emerging therapeutic directions are discussed, including the use of stem cells as drug delivery vehicles, gene therapy carriers, and sources of extracellular vesicles, alon gside strategies to disrupt leukemic stem cell niches and enhance chemotherapy efficacy. While stem cell–based interventions hold considerable promise, their dualistic effects on tumor progression, context-dependent outcomes, and safety concerns underscore the need for further mechanistic studies and carefully designed clinical trials. Collectively, this review emphasizes the evolving role of stem cell–based therapies in leukemia management and identifies future directions for optimizing their clinical application toward long-term disease control and improved patient outcomes.

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