Malcolm A. S. Moore: Human and Murine Embryonic Stem Cell Program

Over the last two years the laboratory has been maintaining the H1 human ES cell line and developing conditions for inducing its differentiation into hematopoietic lineage, lymphoid lineage (including T cell differentiation) and endothelial lineage. By using combinations of cytokines (thrombopoietin, VEGF, cKit ligand, Flt3 ligand, IL-7) and morphogens (BMP’s, Notch ligands) and modifying homeobox protein levels or STAT5 signaling pathways, we are developing systems for generation of human hematopoietic stem cells with the capacity to engraft in NOD/SCID mice.

We are also generating endothelial progenitor cells that can participate in neovascularization in both xenografts tumors and in ischemic limb models in NOD/SCID mice. Hematopoietic stem cells generated in this way could ultimately be used for treatment of leukemia, lymphoma and multiple myeloma, aplastic anemia and genetic disorders of the hematopoietic and immune system. Endothelial progenitors could be used to treat heart disease and ischemia.

Barberi T, Klivenyi P, Calingasan NY, Lee H, Kawamata H, Loonam K, Perrier AL, Bruses J, Rubio ME, Topf N, Tabar V, Harrison NL, Beal MF, Moore MA, Studer L. Neural subtype specification of fertilization and nuclear transfer embryonic stem cells and application in parkinsonian mice. Nat Biotechnol. 2003, 21:1200-7.

Lanza RP, Moore MAS, Wakayama T, Perry ACF, Shieh J-H, Hendrikx J, Leri A, Chimenti S, Monsen A, Nurzynska D, West MD, Kajstura J, Anversa P. Regeneration of the infarcted heart with stem cells derived by nuclear transplantation. Circulation Research, 2004;94:820-7.

Moore, MAS. Commentary: The role of cell migration in the ontogeny of the lymphoid system. Stem Cells Dev. 2004, 13:1-21.

Moore, MAS. The Ontogeny of the Hematopoietic System. in: Handbook of Adult and Fetal Stem Cells, Vol II. Eds Lanza RP, Blau HM, Melton DA, Moore MAS, Thomas ED, Verfaillie CM, Weissman IL, West MD. Elsevier, 2004, pp159-174

Schuringa JJ, Wu K, Morrone G, Moore MA. Enforced activation of STAT5A facilitates the generation of embryonic stem-derived hematopoietic stem cells that contribute to hematopoiesis in vivo. Stem Cells. 2004, 22:1191-1204.