Endogenous hematopoietic reconstitution induced by human umbilical cord blood cells in immunocompromised mice: Implications for adaptive therapy

Human umbilical cord blood (HUCB) cells show promising advantages over bone marrow (BM) cells for a variety of diseases that require transplantation. We observed that lethally irradiated SJL/J mice given a single injection of HUCB cells survive, whereas vehicle-injected mice do not. Because survival is not due to long-term engraftment of HUCB tells, we used this HUCB/mouse model to investigate additional therapeutic benefits of HUCB cells. We inv estigated the mechanism by which HUCB cells accelerated endogenous hematopo iesis in mice that received either lethal (9.5 Gy) or lower-dose (8.0 Gy) r adiation and then were given a single injection of HUCB mononuclear cells. Compared to irradiated control mice, the lethally irradiated, HUCB-injected group showed significant increases in peripheral white blood cell counts, red blood cell indices, and granulocyte-macrophage colony-forming units (CF U-GM) by 3 weeks, In contrast, no significant differences in these paramete rs were observed between control and HUCB-injected mice that received the l o,rer dose of irradiation. Moreover, regardless of the radiation dose, only HUCB-injected mice exhibited immune responses comparable to those of age-m atched normal mice. The clinical relevance of these observations was determ ined in long-term, culture-initiating cell assays with human BR I stem cell s and irradiated (gamma-) HUCB cells. CFU-GM colonies were detectable in cu ltures containing gamma-HUCB cells by day 15, but were undetectable in cult ures without gamma-HUCB cells until day 40, suggesting a hematopoietic stim ulatory role for HUCB cells. Overall, the results indicate that in addition to their use for transplantation, HUCB cells also may be used as an adjuva nt therapy to enhance hematopoietic reconstitution and immunocompetence of the host. This hematopoiesis-enhancing effect represents a heretofore unrec ognized function of HUCB cells. (C) 1999 International Society for Experime ntal Hematology. Published by Elsevier Science Inc.