Murine xenogeneic models of myelodysplastic syndrome: An essential role for stroma cells

The objective of is this article is to review murine xenotransplantation models for myelodysplastic syndromes (MDS). The difficulties in achieving sustained engraftment of MDS cells in immunodeficient mice may lie in innate characteristics of the MDS clones and microenvironmental factors. Engraftment of very low numbers of CD45+ clonal MDS cells has been achieved with intravenous injection; higher rates of engraftment are obtained via the intramedullary route. Coinjection of certain stroma components with hematopoietic cells overcomes limitations of intravenous (IV) administration, allowing for engraftment of high proportions of human CD45+ cells in mouse spleen and marrow. Expression of CD146 on stroma cells conveys an engraftment-facilitating effect. Clonal MDS cells have been propagated for periods beyond 6 months and have been transplanted successfully into secondary recipients. Engraftment of human clonal MDS cells with stem cell characteristics in immunodeficient mice is greatly facilitated by coinjection of stroma/mesenchymal cells, particularly with IV administration. CD146 expression on stroma is an essential factor; however, no model develops the laboratory and clinical features of human MDS. Additional work is needed to determine cellular and noncellular factors required for the full evolution of MDS.