Hypoxic Mesenchymal Stem Cell Secretome Restores Hematopoiesis and Modulates Immune Responses in A Murine Model of Aplastic Anemia
DOI:
https://doi.org/10.48048/tis.2026.13487Keywords:
Aplastic anemia, Mesenchymal stem cell secretome, Hypoxia, Hematopoiesis, Immunomodulation, Busulfan, Murine modelAbstract
Aplastic anemia (AA) is a severe bone marrow failure syndrome characterized by pancytopenia and hypocellular marrow, driven by disrupted hematopoietic stem/progenitor cell (HSPC) pathways and elevated inflammatory cytokines, particularly IFN-γ. Current therapies have limitations, underscoring the need for innovative regenerative approaches. The mesenchymal stem cell (MSC) secretome, especially from hypoxic preconditioning (SH-MSCs), exhibits enhanced paracrine factor secretion, survival, and immunomodulatory efficacy by mimicking the bone marrow niche. This study evaluated the therapeutic potential of SH-MSC secretome in a busulfan-induced AA mouse model. Thirty Balb/c mice were divided into 5 groups: Healthy, AA (control negative), AA + standard medication (control positive), AA + 200 µL SH-MSCs, and AA + 200 µL SH-MSCs + standard medication. AA was induced by busulfan injection. SH-MSCs were isolated from human umbilical cords and cultured under hypoxic conditions (2% O₂). Hematological parameters (RBC, platelets, leukocytes, hemoglobin), gene expression {IL-3, IFN-γ}, EPO levels, and bone marrow cellularity were assessed. The AA model exhibited significant reductions in RBC, platelet, and leukocyte counts compared to healthy controls (p < 0.05). SH-MSCs (200 µL) significantly restored RBC counts, while SH-MSCs alone and combination therapy significantly increased platelet, leukocyte, and hemoglobin levels compared with AA controls (p < 0.05). IFN-γ expression was significantly reduced, and bone marrow cellularity was markedly enhanced by both treatments (p < 0.05). No significant differences were observed between SH-MSCs alone and combination therapy for RBCs, hemoglobin, or other parameters (p > 0.05). These findings demonstrate that hypoxic preconditioned MSC secretome effectively promotes hematopoiesis, suppresses inflammation, and restores bone marrow function in AA, offering comparable efficacy to combination therapy and strong potential as a novel standalone or adjunctive treatment.
HIGHLIGHTS
- Hypoxia-conditioned MSC (SH-MSC) secretome improves blood recovery in a busulfan-induced aplastic anemia model.
- SH-MSCs support red blood cell production and bone marrow repair via paracrine and immune effects.
- SH-MSC treatment restores RBCs, platelets, and white blood cells, and lowers IFN-γ levels.
- SH-MSCs show similar effectiveness to standard immunosuppressive therapy, suggesting strong clinical potential.
GRAPHICAL ABSTRACT
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