Postnatal cytokines and boosts improve chimerism and hematological parameters in beta-thalassemic mice transplanted in utero.
We have developed a murine model of in utero transplantation in nonanemic, beta-thalassemic mice to study chimerism, tolerance, and changes in hematological parameters in response to cytokines and postnatal boosts with donor cells. We have documented improved survival of homozygous fetuses by 40% as compared with controls. Low-level, mixed chimerism was improved by postnatal cytokine therapy and boosts and was associated with improvement in hemoglobin levels, reticulocyte counts, and iron stores. Cytotoxicity assays demonstrated higher responses to donor cells in control mice as compared with in utero transplanted animals (at 50:1 effector to target ratios, transplanted mice showed 8.66% target lysis and control mice showed 51.85% target lysis, P=0.0003), indicating tolerance. The combination of prenatal tolerance to allogeneic cells with postnatal boosts in primed hosts may become an effective, nontoxic strategy for the improvement of hemolytic anemia in beta-thalassemic patients.
Donahue
J
J
UCSD Blood and Marrow Transplantation Division, 9500 Gilman Drive, #0062, La Jolla, CA 92093-0062, USA.
Gilpin
E
E
Young
D
D
Carrier
E
E
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D001790:Blood Physiological Phenomena; D017690:Cell Transplantation; D002678:Chimera / Q000502:physiology*; D016207:Cytokines / Q000494:pharmacology*; D004921:Erythropoietin / Q000494:pharmacology; D005333:Fetus / Q000276:immunology; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D007108:Immune Tolerance; D008099:Liver / Q000166:cytology* / Q000196:embryology / Q000601:surgery; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D019089:Stem Cell Factor / Q000494:pharmacology; D017086:beta-Thalassemia / Q000196:embryology* / Q000503:physiopathology*
D016207:Cytokines; D019089:Stem Cell Factor; D004921:Erythropoietin; D016179:Granulocyte Colony-Stimulating Factor