Faculty Research 1990 - 1999

Title

Multiple high cell dose injections of normal marrow into newborn jaundiced mice dramatically prolong life despite transient repopulation.

Document Type

Article

Publication Date

1999

Keywords

Animals-Newborn, Blood-Cells: cy, Bone-Marrow-Transplantation, Cell-Division, Female, Genetic-Markers, Glucose-6-Phosphate-Isomerase: ge, Human, Infant-Newborn, Jaundice-Neonatal: th, Life-Expectancy, Male, Mice, Mice-Inbred-C57BL, Mice-Mutant-Strains, SUPPORT-U-S-GOVT-P-H-S

JAX Source

Exp Hematol 1999 May;27(5):966-71

Grant

CA34196/CA/NCI, RO1DK27726/DK/NIDDK, RO1HL29305/HL/NHLBI

Abstract

Jaundiced (ja/ja) mice have a severe hemolytic anemia caused by deficiency of the erythroid cytoskeletal protein beta-spectrin. Unless they are transfused, 99% of the mutant mice die after birth. Here, we test a new therapy involving multiple, high cell dose marrow injections into newborn non-ablated recipients. The ja/ja and normal newborn mice were injected intravenously with a total of 8.7 x 10(6) genetically marked +/+ marrow cells/g body weight. Donor and host red blood cells were quantified and the status of the recipients monitored. The jaundiced but not the normal recipients had up to 57% replacement with donor red cells by 9 weeks. The treatment significantly increased red cell counts and extended the average lifespan to 5 months beyond that previously reported for ja/ja mice transfused at birth. Replacement was limited to red cells. The donor cells disappeared in three of five mutant mice alive beyond 27 weeks. Marrow from a 48-month-old ja/ja recipient no longer positive for donor cells was injected into a secondary host. The recipient acquired the blood phenotype of the primary ja/ja host. The possibility that the marker was not well tolerated following multiple cell injections was investigated in normal adult mice injected with a total of 5.3 x 10(6) marrow cells/g body weight. Recipients became chimeric (>38% donor red and white cells) long-term (>12 months). The results indicate donor stem cells (a) prolong life in the jaundiced mice, but (b) do not survive long-term when injected into newborn mice. We conclude that destructive mechanisms may not be limited to ja/ja red cells.

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