Xenograft models for pediatric malignancies - Where do we stand?

Xenograft models using immune-deficient mice have been established for a variety of pediatric malignancies, particularity leukemias. We have recently been able to improve the ALL xenograft model by using NOD-SCID instead of classical SCID mice as recipients for human leukemic cells (Baersch et al., submitted). As few as 10,000 ALL cells from a patient with pre-pre-B-ALL were sufficient to reproduce the disease in mice. Interestingly, human tumor cells seem also to be able to grow in immune-deficient mice in a manner similar to that in patients. A scientist from the Childrens Hospital Los Angeles could demonstrate that human neuroblastoma cells after intravenous injection disseminate to the liver, adrenal glands and bone marrow of transplanted SCID mice (Int. J. Cancer 67:379, 1996). Our own preliminary results suggest that Ewing tumor cells after intravenous injection can cause bone tumors in transplanted NOD-SCID mice. This orthotopic growth represents a great improvement to the unphysiolocial subcutanous tumor growth in nude mice. Strategies will be discussed how these NOD-SCID mice models can now be used to study homing/metastasis of malignant cells and to identify normal and malignant stem populations in pediatric leukemias and solid tumors.