This application is in response to PAR-03-063 entitled: """"""""Competitive Supplement for Human Embryonic Stem Cell Research"""""""". The application is meant to supplement my HL67384 grant entitled: """"""""Cytokine Enhancement of Myeloid Progenitor Cell Survival"""""""".
One aim of this grant was to investigate the cellular effects of Stromal Cell Derived Factor. (SDF-1 = CXCL12) alone, and then in combination with either Flt3-Ligand (FL) or Thrombopoietin (TPO), on prolonging survival of human and murine myeloid progenitor cells (MPC) and murine stem cells and growth factor-dependent hematopoietic cell lines that undergo apoptosis upon withdrawal of growth factors.
The aims of this supplement, consistent with that of HL67384, are: 1) Define optimal culture conditions for growth and survival of human embryonic stem (HES) cells and their differentiation into embryoid bodies (EBs) containing MPC. Characteristic HES cells and HES cell-derived MPC for mRNA and surface expression of CXCR4 (receptor for SDF-1/CXCL12) and CD26 (dipeptidylpeptidase IV that can cleave SDF-1/CXCL 12 into an inactive truncated form). Since SDF-1/CXCL 1 synergizes with stem cell factor (SCF, also termed steel factor), thrombopoietin (TPO), or Flt3-1igand (FL) to enhance survival of MPC subjected to delayed addition of growth factors, characterize expression of c-kit (SCF-receptor), c-mI (TPO-receptor), and Flt-3 (FL-receptor) on HES cells and MPC found in EBs. 2) Evaluate influence of SDF-1/CXCL 12-CXCR4 axis and CD26 on enhancement of the survival/anti-apoptosis of HES cells and/or HES cell-derived MPC. Also, evaluate the effects of the SDF-1/CXCL12-CXCR4 axis in combination with SCF/c-kit, TPO/c-mpl, or FL/Flt-3 ligand-receptor interactions. These studies should increase current understanding of the cytokines/receptors involved in survival of HES and their hematopoietic cell progeny. ? ?
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