Safety of Repeated Mesenchymal Stem Cell Transplantation in Solid Tumors: Evidence from an Immunocompetent EGFR-Mutant Lung Cancer Model
Keywords:
Mesenchymal stem cells, repeated transplantation, EGFR-mutant lung cancer, immunocompetent model, tumor safetyAbstract
Background: Mesenchymal stem cells (MSCs) have therapeutic promise, but their safety in repeated intravenous administration remains debated, especially regarding solid tumor promotion. Most prior studies used immunodeficient models, limiting clinical translation. This review evaluates safety evidence from an immunocompetent EGFR-mutant lung cancer model.
Methods: A structured literature review was performed on PubMed, Scopus, ScienceDirect, and Google Scholar up to 2026 using MSC, safety, repeated transplantation, and EGFR-mutant lung cancer keywords. Relevant English publications were synthesized narratively.
Results: In an immunocompetent EGFR-mutant lung adenocarcinoma model, repeated human umbilical cord MSC (hUC-MSC) administration did not accelerate tumor occurrence or progression. Intravenously infused MSCs underwent rapid pulmonary entrapment and clearance without cumulative toxicity, organ damage, or distant metastasis. Molecular analysis revealed that repeated MSC treatment significantly downregulated pro-tumorigenic cytokines including IL-6 and IL-8, preserved the physiological M1/M2 macrophage balance, and upregulated IFN-γ expression. This IFN-γ elevation correlated with expanded CD8+ cytotoxic T-cell infiltration into the tumor microenvironment, indicating sustained immune surveillance rather than immunosuppression. No pro-angiogenic shift (VEGF-A, VEGF-C, VEGF-D) was observed. Ki67 proliferation indices in alveolar epithelial cells remained unchanged compared to controls.
Conclusion: Repeated intravenous MSC transplantation does not promote tumorigenesis in an immunocompetent EGFR-mutant lung cancer model, supporting its systemic safety even under pre-existing oncogenic conditions.
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