Normal Production of Erythrocytes by Mouse Marrow Continuous for 73 Months

Abstract

Marrow cell transplants from old and young control donors were carried in genetically anemic W/Wv recipients whose anemias were cured by successful transplants. After a maximum of 36 months and four serial transplants, marrow cell lines from both old and younger control donors continued to produce erythrocytes normally. The oldest marrow cell lines had produced erythrocytes normally for 73 months.Normal erythrocyte production was demonstrated by: (1) cure of the anemia in W/WV recipients, (2) normal rather than delayed recovery rate of cured recipients after severe bleeding, and (3) normal rather than ineffective response of cured recipients to erythropoietin. Hemoglobin patterns, tested in cured WIWv recipients after the first transplantation, showed that at least 90% of the circulating erythrocytes were of the donor type even in donor lines that had produced erythrocytes continuously for 45 months and were recovering from severe bleeding. Concentrations of cells capable of forming macroscopic spleen colonies were more than two orders of magnitude higher in W/Wv mice cured by old or younger marrow than in uncured W/WI mice. Nevertheless, colony-forming unit concentrations declined slowly with successive transplants, and the decline seemed more pronounced at the fourth transplant in old than in younger cell lines.The hypothesis is suggested that senescence is caused by declines in function of only a few vital cell types. The system for comparing old and younger marrow cell lines offers a model for experiments to test this hypothesis and to identify the cell types whose decline causes aging.

When stem cells grow old: phenotypes and mechanisms of stem cell aging

“…HSCs reside in the bone marrow in adult mammals and are responsible for blood formation. In early studies, bone marrow cells from young and old mice were found to display similar reconstitution abilities in transplantation assays (Harrison, 1973;Ogden and Micklem, 1976;Harrison et al, 1978). In fact, serial transplantation studies have shown that normal HSCs can sustain blood formation for multiple lifetimes (Harrison, 1979).…”

A new mechanism for the aging of hematopoietic stem cells: aging changes the clonal composition of the stem cell compartment but not individual stem cells

“…Like all stem cells, hematopoietic stem cells (HSCs) self-renew, and serial transplantation studies show that populations of HSCs can live much longer than the donor from which they were originally isolated. 1 HSCs express telomerase, necessary for chromosome stability during cell division. 2 Together, these observations supported the idea of an immortal HSC.…”

Loss of proliferative capacity in immunohemopoietic stem cells caused by serial transplantation rather than aging.

“…Some investigators find defects in stem cells from old individuals (6)(7)(8), whereas others report no difference in functional abilities of old and young stem cells (9)(10)(11). Recently, Albright and Makinodan (8) suggested that old stem cells cannot multiply as rapidly as can young stem cells immediately after transplantation, although they are able to multiply and differentiate into normally functional immunohemopoietic cells if given adequate time.…”