Martin Carroll, M.D.
2014 Grant Recipient
Development of Xenotransplantation Models of Myelodysplastic Syndromes
Basic Science Research Grant 2014
Myelodysplastic syndromes (MDS) are a group of diseases that are poorly understood. The poor understanding derives in part from the diversity of the diseases and the lack of animal models. We have worked to develop an animal model of MDS syndromes by engrafting cells from human patients with MDS into immune compromised mice that will allow the human cells to grow. Cells injected combine both the blood cells and bone marrow stromal cells designated mesenchymal stem cells (MSC). We have shown that when these are co-injected, mice initially engraft with cells that appear to represent different stages of MDS. All lineages of blood cells are present demonstrating that we engrafted a MDS stem cell. However, our initial studies demonstrate that some MDS samples engraft for long periods of time in immune compromised mice, whereas others appear to engraft for only a few months. Engraftment was not modified significantly by the presence of human growth factors nor the co-administration of human MSC’s. The overall level of engraftment is quite low making clinical studies of novel therapeutics in these models unlikely to be interpretable.
Maria Krevvata, Xiaochuan Shan, Chenghui Zhou, Cedric Dos Santos, Georges Habineza Ndikuyeze, Anthony Secreto, Joshua Glover, Winifred Trotman, Gisela Brake-Silla, Selene Nunez-Cruz, Gerald Wertheim, Hyun-Jeong Ra, Elizabeth Griffiths, Charalampos Papachristou, Gwenn Danet-Desnoyers, and Martin Carroll, Cytokines increase engraftment of human acute myeloid leukemia cells in immunocompromised mice but not engraftment of human myelodysplastic syndrome cells, haematologica 2018, 10.3324/haematol.2017.183202.