Multiple high cell dose injections of normal marrow into newborn jaundiced mice dramatically prolong life despite transient repopulation.
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.
Barker
J E
JE
The Jackson Laboratory, Bar Harbor, ME 04609, USA. jeb@aretha.jax.org
Kaysser-Kranich
T M
TM
Hamblen
N
N
Deveau
S
S
D000818:Animals; D000831:Animals, Newborn; D001773:Blood Cells / Q000166:cytology; D016026:Bone Marrow Transplantation; D002455:Cell Division; D005260:Female; D005819:Genetic Markers; D005956:Glucose-6-Phosphate Isomerase / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D007567:Jaundice, Neonatal / Q000628:therapy*; D008017:Life Expectancy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains
D005819:Genetic Markers; D005956:Glucose-6-Phosphate Isomerase