Risks and mechanisms of oncological disease following stem cell transplantation

Unique biological properties of stem cells make them a precious source of cell material for treatment of a number of pathological conditions. Among issues inhibiting transition of stem cell technologies to the clinics, the risk of oncological complications of stem cell-based therapies is the most critical. A massive amount of clinical and experimental data demonstrates that both hematological (including acute and chronic myeloid leukemia) and non-hematological (including teratoma and non-teratoma tumors) malignancies could arise from donor stem cells of different types. A wide spectrum of mechanisms could underlie the development of oncological disease in recipients, including: i) blast transformation of proliferating donor stem cells under persistent action of certain factors in the recipient, thus causing de novo malignancies; ii) contamination of donor cell material with malignant cells; iii) transmission of particular viral subtypes with donor stem cells, combined with immunosuppression therapy effects; iv) uncontrollable proliferation of residual undifferentiated stem cells of various plasticity; and v) karyotypic instability in stem cells following prolonged culturing/expansion in vitro. Potential preventive strategies are diverse and include i) high-throughput cell sorting-based strategies; ii) introduction of suicide genes into the donor stem cell genome; iii) application of apoptosis-inducing epigenetic factors; and some other options.