The Therapeutic Potential of Stem Cells in Leukemia: Mechanisms and Clinical Directions

نویسندگان

1 Department of Molecular and Cell Biology, Faculty of Advanced Sciences and Technology, Islamic Azad University Tehran Medical Sciences, Tehran, Iran

2 Applied Microbiology Research Center, Biomedicine Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran

doi
10.30491/ijmr.2025.555989.1353
چکیده

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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