Cyclic ADP-ribose generation by CD38 improves human hemopoietic stem cell engraftment into NOD/SCID mice.

SPECIFIC AIMSCyclic ADP-ribose (cADPR), a potent and universal intracellular calcium mobilizer, has recently been shown to behave as a new hemopoietic cytokine as it stimulates in vitro the proliferation of human hemopoietic progenitors (HHP), both mature-committed (colony-forming cells, CFC) and immature-uncommitted (long-term culture initiating cells, LTC-IC). Therefore, we investigated in vivo the effect of cADPR on the self-renewal and expansion of hemopoietic stem cells (HSC), i.e., the most immature HHP responsible for repopulation of the bone marrow (BM), by analyzing their capacity of engraftment into irradiated NOD/SCID mice.PRINCIPAL FINDINGS1. In vitro priming with cADPR increases short-term HHP engraftment into NOD/SCID miceCord blood-derived human mononuclear cells (MNC) were first incubated for 24 h with either 100 μM ADPR (group 1, controls) or 100 μM cADPR (group 2), then infused (11.8×106 MNC) into irradiated NOD/SCID mice (4 animals for each point, n=6). Mice were killed at days +20, +60...