Preserving Bone Marrow Cells After Peptide Receptor Radiotherapy
Mentor: Sue M. O'Dorisio
We hypothesize that hematopoietic stem cells can be protected from lethal irradiation by mesenchymal stem cells and/or drugs that prevent their differentiation. Human cord blood will be obtained from our cord blood bank and cultured in vitro with valproic acid (a histone deacetylase inhibitor) to enrich for hematopoietic stem cells (HSC). Additionally, mesenchymal stem cells (MSC) will be cultured from the cord itself. HSC and MSC will characterized by flow cytometry and co-cultured in various ratios to find the optimum number of MSC to sustain HSC and maintain them as stem cell with little or no differentiation. These HSC/MSC co-cultures will be exposed in vitro to increasing levels of 212Pb-Pentixather, a novel radiotherapeutic drug that targets the cytokine receptor, CXCR4, expressed on HSC. We will determine whether MSC and/or specific drugs can protect human hematopoietic stem cells from radiation. Success in these experiments will enable delivery of curative levels of 212Pb-Pentixather to children with tumors such as neuroblastoma that express high levels of CXCR4.