Mobilization of hematopoietic stem cells for transplantation: review of mechanisms and modern drugs

Hematopoietic stem cell transplantation (HSCT) is a modern method of treatment for oncohematological and other severe blood diseases. To prepare transplants, HSC mobilization is mainly used, followed by leukapheresis and assessment of CD34+ cells; the minimum required number for reliable repopulation is 2×10⁶ CD34+ cells/kg, while an increase in the cellularity of the transplant >5×10⁶ CD34+ cells/kg is associated with more positive clinical outcomes. The review presents the most relevant profile of surface markers for HSCs, describing the role of each marker in the proliferation and mobilization of CD34+ cells. The biological mechanisms of HSC retention and exit from the bone marrow niche, such as the CXCR4/SDF-1 (CXCL12) axis and interactions between VLA-4 and VCAM-1/fibronectin, have been analyzed. The review presents current approaches to pharmacological mobilization of HSCs, with a detailed discussion of the mechanisms involved. Classical agents, such as granulocyte colony-stimulating factor (G-CSF) and plerixafor, demonstrate effectiveness in most patients, but are associated with side effects and mobilization failures in ~10–15 % of donors. Promising drugs, including selective CXCR4 antagonists (motixafortide, balixafortide), CXCR2 agonists (MGTA-145), and approaches targeting the microenvironment of HSCs, such as inhibition of heparan sulfate synthesis, activation of the neurogenic axis through capsaicin-stimulated nociceptive neurons, and MMP-mediated matrix remodeling are discussed. The review analyzes the advantages (rapid and productive mobilization, potentially more functional transplants) and limitations (safety, translation of preclinical data, and requirement of clinical validation). The review addresses the potential of using the latest drugs and alternative targets in practice. Also emphasized the need for comparative clinical studies, development of biomarkers, and personalized mobilization algorithms to optimize the outcomes of HSC transplantation.

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