Adult and Umbilical Cord Blood Hematopoietic Stem Cell Expansion

The laboratory has an active program for ex vivo culture and expansion of hematopoietic stem cells from adult marrow, G-CSF mobilized peripheral blood and umbilical cord blood for potential use for unrelated donor transplantation for treatment of leukemia, lymphoma and multiple myeloma, aplastic anemia and genetic disorders of the hematopoietic and immune system. 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 expanding pluripotential stem cells as well as modifying differentiation along specific pathways to facilitate e.g platelet reconstitution, T lymphocyte recovery. We have developed gene therapy strategies in which human hematopoietic stem cells can be genetically modified by retroviral or lentiviral gene transduction. Such gene therapy may be of clinical value for treatment of genetic disease of the immune and blood cell forming systems.

Moore MAS. Colony-stimulating factors: Basic principles and preclinical studies. In: Rosenberg SA, ed. Principles and Practice of the Biologic Therapy of Cancer, 3rd ed. Lippincott Williams & Wilkins, Philadelphia, 2000, 113-40.

Han W, Ye Q, Moore MAS. A soluble form of human Delta-Like-1 inhibits differentiation of hematopoietic progenitor cells. Blood 2000; 95:1616-1625.

Moore MAS. Commentary: Umbilical cord blood: An expendable resource. J. Clin Invest. 2000;105:855-56

Moore MAS. Hematopoietic growth factors. In: Humes HD, ed. Kelley’s Textbook of Internal Medicine. 4th edition. Philadelphia: Lippincott Williams & Wilkins, 2000.

Moore MAS. The hematopoietic system and hematopoiesis. In: Knowles DM, ed. Neoplastic Hematopathology. 2nd ed. Williams and Wilkins. 2000, pp. 1-42.

Moore MAS, Han W, Ye Q. Notch signaling during hematopoiesis. In: L. Zon, ed. Hematopoiesis: A developmental approach. New York: Oxford University Press, 2001.

Feugier P, Jo D-Y, Shieh J-H, MacKenzie KL, Rafii S, Crystal RG, and Moore, MAS. Ex vivo Expansion of Stem and Progenitor Cells in Co-Culture of Mobilized Peripheral Blood CD34+ Cells on Human Endothelium Transfected with Adenovectors Expressing Thrombopoietin, C-kit Ligand and Flk-2 Ligand. J of Hematotherapy & Stem Cell Research 2002;11:127-38.

Heissig B, Hattori K, Dias S, Friedrich M, Ferris B, Hackett N, Crystal RG, Besmer P, Lyden D, Moore MAS, Werb Z, Rafii S. Recruitment of stem cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand. Cell 2002; 109:625-637

Moore MAS. Cytokine and chemokine networks influencing stem cell proliferation, differentiation, and marrow homing. J Cell Biochem Suppl. 2002;38:29-38.

Hattori K, Heissig B, Wu Y, Dias S, Tejada R, Ferris B, Hicklin DJ, Zhu Z, Bohlen P, Witte L, Hendrikx J, Hackett NR, Crystal RG, Moore MA, Werb Z, Lyden D, Rafii S. Placental growth factor reconstitutes hematopoiesis by recruiting VEGFR1(+) stem cells from bone-marrow microenvironment. Nat Med. 2002; 8:841-849.

Moore MAS. In vitro and in vivo hematopoiesis. In: Zucker-Franklin, Greaves MF, Grossi CE, Marmont Am, eds: Atlas of Blood Cells: Function and Pathology. 3rd edition. Arti Grafiche Salea, Milan. 2003, pp1-38.

Rafii S, Avecilla S, Shmelkov S, Shido K, Tejada R. Moore MA, Heissig B, Hattori K. Angiogenic factors reconstitute hematopoiesis by recruiting stem cells from bone marrow microenvironment. Ann NY Acad Sci 2003 996:49-60.

Bond HM, Mesuraca M, Carbone E, Bonelli P, Agosti V, Amodio N, De Rosa G, Di Nicola M, Gianni MA, Moore MAS, Hata A, Grieco M, Morrone G, Venuta S. Early hematopoietic zinc finger protein (EHZF), the human homologue for Evi3 is highly expressed in primitive human hematopoietic cells. Blood 2003. 103:2062-70.

Agosti V, Corbacioglu S, Ehlers I, Waskow C, Sommer G, Berrozpe G, Kissel H, Tucker CM, Manova K, Moore MA, Rodewald H-R, Besmer P. Critical role for Kit-mediated Src kinase but not PI 3-kinase signaling in pro T and pro B cell development. J Exp Med. 2004, 199:876-78.

Gammaitoni L, Weisel KC, Gunetti M, Wu KD, Bruno S, Pinelli S, Bonati A, Aglietta M, Moore MAS, Piacibello W. Elevated telomerase activity and minimal telomere loss in cord blood long-term cultures with extensive stem cell replication. Blood 2004, 103:4440-8.

Moldenhauer A, Shieh J-H, Pruss A, Salama A, Moore MAS. Tumor necrosis factor alpha enhances the adenoviral transduction of CD34(+) hematopoietic progenitor cells. Stem Cells. 2004, 22:283-291.

Ye Q, Shieh J-H, Morrone G, Moore MAS. Expression of constitutively active Notch4 (Int-3) modulates myeloid proliferation and differentiation and promotes expansion of hematopoietic progenitors. Leukemia, 2004, 18:777-87.

Project Members