[HTML][HTML] Delta-1 enhances marrow and thymus repopulating ability of human CD34+CD38 cord blood cells

K Ohishi, B Varnum-Finney… - The Journal of clinical …, 2002 - Am Soc Clin Investig
K Ohishi, B Varnum-Finney, ID Bernstein
The Journal of clinical investigation, 2002Am Soc Clin Investig
We investigated the effect of Notch signaling, a known regulator of cell fate in numerous
developmental systems, on human hematopoietic precursors. We show that activation of
endogenous Notch signaling in human CD34+ CD38–cord blood precursors with
immobilized Delta-1 in serum-free cultures containing fibronectin and hematopoietic growth
factors inhibited myeloid differentiation and induced a 100-fold increase in the number of
CD34+ cells compared with control cultures. Immobilized Delta-1 also induced a multifold …
We investigated the effect of Notch signaling, a known regulator of cell fate in numerous developmental systems, on human hematopoietic precursors. We show that activation of endogenous Notch signaling in human CD34+ CD38–cord blood precursors with immobilized Delta-1 in serum-free cultures containing fibronectin and hematopoietic growth factors inhibited myeloid differentiation and induced a 100-fold increase in the number of CD34+ cells compared with control cultures. Immobilized Delta-1 also induced a multifold expansion of cells with the phenotype of common lymphoid precursors (CD34+ CD7+ CD45RA+) and promoted the development of cytoplasmic CD3+ T/NK cell precursors. IL-7 enhanced the promotion of T/NK cell differentiation by immobilized Delta-1, but granulocytic differentiation occurred when G-CSF was added. Transplantation into immunodeficient mice showed a substantial increase in myeloid and B cell engraftment in the marrow and also revealed thymic repopulation by CD3+ T cells due to cells being cultured for a longer period with immobilized Delta-1. These data suggest that Delta-1 can enhance myeloid and lymphoid marrow-repopulating ability and promote the generation of thymus-repopulating T cell precursors.
The Journal of Clinical Investigation