Evaluation of stem cell reserve using serial bone marrow transplantation and competitive repopulation in a murine model of chronic hemolytic anemia.
Serial transplantation and competitive repopulation were used to evaluate any loss of self-replicative capacity of bone marrow stem cells in a mouse model with increased and persistent hemopoietic demands. Congenic marrows from old control and from young and old mice with hereditary spherocytic anemia (sphha/sphha) were serially transplanted at 35-day intervals into normal irradiated recipients. Old anemic marrow failed or reverted to recipient karyotype at a mean of 3.5 transplants, and young anemic marrow reverted at a mean of 4.0 transplants, whereas controls did so at a mean of 5.0 transplants. In a competitive assay in which a mixture of anemic and control marrow was transplanted, the anemic marrow persisted to 10 months following transplantation; anemic marrow repopulation was greater if anemic marrow sex matched with the host. It is possible that lifelong stress of severe anemia decreases stem cell reserve in the anemic sphha/sphha mouse marrow. However, marginal differences in serial transplantation number and the maintenance of anemic marrow in a competition assay would suggest that marrow stem cells, under prolonged stress, are capable of exhibiting good repopulating and self-replicating abilities.
D000375:Aging; D000818:Animals; D001853:Bone Marrow / Q000473:pathology / Q000528:radiation effects; D016026:Bone Marrow Transplantation; D002453:Cell Cycle / Q000528:radiation effects; D002908:Chronic Disease; D003114:Colony-Forming Units Assay; D004195:Disease Models, Animal; D004906:Erythrocyte Count; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000473:pathology / Q000528:radiation effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010198:Pancytopenia / Q000097:blood / Q000473:pathology; D011828:Radiation Chimera; D013103:Spherocytosis, Hereditary / Q000097:blood* / Q000473:pathology / Q000503:physiopathology; D013154:Spleen / Q000473:pathology