Abstract: The present application discloses strategies to recruit and mobilize stem cells using S1P receptor selective agonists and antagonists as wells as regulators of chemokine receptors. In an in vivo ischemic model, S1P1/S1P3 activation with FTY720 impeded inflammatory cell infiltration and recruited endothelial progenitor cells (EPCs) with the potential to increase microvascular remodeling. S1P3 expression on marrow-derived cells was essential for this remodeling. Concurrent systemic S1P3 and CXCR4 antagonism mobilized hematopoietic stem cells (HSCs) with the ability to engraft and repopulate blood cells. Pre-treatment of donor HSCs with FTY720 increased homing toward SDF-1 and improved engraftment in marrow. FTY720-coated bone allografts coupled with systemic administration of VPC01091 enhanced bone allograft integration and new bone formation in bone defects. MSCs pre-treated with FTY720 exhibited increased migration toward SDF-1, a CXCR4+ ligand.

Abstract: A method of decreasing NFATc2 activity in a lymphocyte includes administering to the lymphocyte an amount of an NFATc2 mRNA antagonist that binds to a binding site on the 3?UTR of NFATc2 mRNA effective to decrease the activity of NFATc2 mRNA in the lymphocyte.

Abstract: The present invention provides for enhancing engraftment by co-infusing at least two partially HLA matched umbilical cord blood (“UCB”) units. The invention further provides for positive C3a mediated priming on responsiveness to doses of SDF-1 and C3a induced incorporation of CXCR4 in membranes in HSC and progenitors. The invention further provides for enhancing the homing of UCB HSC and progenitors via the SDF-1/CXCR4 pathway and that C3a and LL-37 are useful for this method. It is also disclosed herein that fragments of C3a (e.g., des-Arg) are effective in the methods of the invention, including enhancing homing of HSPCs to BM. The invention further encompasses the disclosure herein of NFAT1 regulation post-transcriptionally by both mir-184 and IFN-?. The present invention further provides for measuring and using differences between UCB and adult CD4+/45RA+ T-cells as a means of defining strategies to enhance optimal allogeneic stem cell transplantation outcomes.

Abstract: A method of decreasing NFATc2 activity in a lymphocyte includes administering to the lymphocyte an amount of an NFATc2 mRNA antagonist that binds to a binding site on the 3?UTR of NFATc2 mRNA effective to decrease the activity of NFATc2 mRNA in the lymphocyte.

Abstract: The present application discloses strategies to recruit and mobilize stem cells using S1P receptor selective agonists and antagonists as wells as regulators of chemokine receptors. In an in vivo ischemic model, S1P1/S1P3 activation with FTY720 impeded inflammatory cell infiltration and recruited endothelial progenitor cells (EPCs) with the potential to increase microvascular remodeling. S1P3 expression on marrow-derived cells was essential for this remodeling. Concurrent systemic S1P3 and CXCR4 antagonism mobilized hematopoietic stem cells (HSCs) with the ability to engraft and repopulate blood cells. Pre-treatment of donor HSCs with FTY720 increased homing toward SDF-1 and improved engraftment in marrow. FTY720-coated bone allografts coupled with systemic administration of VPC01091 enhanced bone allograft integration and new bone formation in bone defects. MSCs pre-treated with FTY720 exhibited increased migration toward SDF-1, a CXCR4+ ligand.

Abstract: A method of decreasing NFATc2 activity in a lymphocyte includes administering to the lymphocyte an amount of an NFATc2 mRNA antagonist that binds to a binding site on the 3?UTR of NFATc2 mRNA effective to decrease the activity of NFATc2 mRNA in the lymphocyte.

Abstract: The invention provides, among other things, novel cell populations of CD133? cells. Some aspects of the invention provide endothelial generating cells (EGCs), such as, for example, CD34?CD133?CD73?CD14+CD11b+CXCR4+ cells. The invention further provides related compositions, kits and methods of isolating the novel EGC cell populations. Also provided by the invention are methods of inducing vascularization is subjects in need thereof, such as in subjects afflicted with ischemia or vascular occlusion, by administering to the subject the EGCs alone or in combination with other cell populations, polypeptides, compounds or other agents.

Abstract: The invention provides, among other things, methods for treating an ischemic tissue in a subject in need thereof. The invention further provides methods for increasing the blood flow to an ischemic tissue in a subject in need thereof, such as to ischemic myocardium. The invention further provides cell-based formulations and related kits.

Abstract: The invention provides, among other things, methods for treating an ischemic tissue in a subject in need thereof. The invention further provides methods for increasing the blood flow to an ischemic tissue in a subject in need thereof, such as to ischemic myocardium. The invention further provides cell-based formulations.