The Fate of Serially Transplanted Bone Marrow Cell Populations From Young and Old Donors

Ogden, Darren A.; Mickliem, H S

doi:10.1097/00007890-197609000-00010

Cited by 140 publications

(73 citation statements)

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“…Historically, the impact of aging on primitive hematopoietic cells has been studied by using numerous assays including colonyforming unit-spleen (CFU-S) activity (5), cobblestone area-forming cell (CAFC) activity (9), BM transplantation (6, 7), and serial transplantation (8). These studies, however, often lead to conflicting conclusions with CFU-S and CAFC activities, suggesting considerable age-dependent differences (5, 9), whereas single or serial transplantation experiments of BM suggest that aging had little impact on stem cell function (7,8).…”

mentioning

confidence: 99%

“…These studies, however, often lead to conflicting conclusions with CFU-S and CAFC activities, suggesting considerable age-dependent differences (5, 9), whereas single or serial transplantation experiments of BM suggest that aging had little impact on stem cell function (7,8). The discrepant conclusions of these studies, however, could be partly caused by differences in mouse strains used, because strain-dependent increases or decreases in primitive hematopoietic cell frequency and function with age have been reported (9).…”

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confidence: 99%

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Cell intrinsic alterations underlie hematopoietic stem cell aging

Rossi

Bryder²,

Zahn³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

997

115

1,068

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Loss of immune function and an increased incidence of myeloid leukemia are two of the most clinically significant consequences of aging of the hematopoietic system. To better understand the mechanisms underlying hematopoietic aging, we evaluated the cell intrinsic functional and molecular properties of highly purified long-term hematopoietic stem cells (LT-HSCs) from young and old mice. We found that LT-HSC aging was accompanied by cell autonomous changes, including increased stem cell self-renewal, differential capacity to generate committed myeloid and lymphoid progenitors, and diminished lymphoid potential. Expression profiling revealed that LT-HSC aging was accompanied by the systemic down-regulation of genes mediating lymphoid specification and function and up-regulation of genes involved in specifying myeloid fate and function. Moreover, LT-HSCs from old mice expressed elevated levels of many genes involved in leukemic transformation. These data support a model in which age-dependent alterations in gene expression at the stem cell level presage downstream developmental potential and thereby contribute to age-dependent immune decline, and perhaps also to the increased incidence of leukemia in the elderly.leukemia ͉ microarray ͉ ontogeny ͉ lineage potential

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confidence: 99%

mentioning

confidence: 99%

Cell intrinsic alterations underlie hematopoietic stem cell aging

Rossi

Bryder²,

Zahn³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

997

115

1,068

View full text Add to dashboard Cite

show abstract

“…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.…”

mentioning

confidence: 99%

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

Harrison¹,

Astle²,

Delaittre³

1978

The Journal of Experimental Medicine

211

120

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Marrow stem cell lines from old donors and those from young controls gave equally rapid rates of colony growth on spleens of irradiated mice. Old and young stem cell lines competed equally well with chromosomally marked marrow stem cells from a young donor in producing cell types that are stimulated by bleeding; old cells competed 70% as well as young in producing cell types stimulated by phytohemagglutinin (PHA) in vitro. After a single serial transplantation, the rates of colony growth declined 1.5- to 2.5-fold, and the ability to compete declined 2- to 4-fold for bleeding-stimulated and 4- to 10-fold for PHA-stimulated cells. Thus, immediate stem cell proliferative capacities decline much more after one serial transplantation than after a lifetime of normal function.

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“…Most models assume that the self-renewal potential of stem cells is finite, as evidenced by serial transfer experiments (14) and supported by the Hayflick limit concept (15). Stochastic and deterministic models (reviewed in 12) attribute different weights to the roles played by intrinsic and microenvironmental factors in the decision of selfrenewal or differentiation.…”

Section: Differentiation In the Hematopoietic Systemmentioning

confidence: 99%

The hematopoietic stroma

Nardi

Alfonso

1999

Braz J Med Biol Res

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All blood cells are derived from a small common pool of totipotent cells, called hematopoietic stem cells. The process is strictly regulated by the hematopoietic microenvironment, which includes stromal cells, extracellular matrix molecules and soluble regulatory factors. Several experimental in vitro assays have been developed for the study of hematopoietic differentiation, and have provided valuable information on the stroma, which includes, among other cell types, macrophages, fibroblasts, adipocytes, and endothelial cells. The composition, ontogeny, and function in physiological as well as pathological conditions of stroma are discussed.

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The Fate of Serially Transplanted Bone Marrow Cell Populations From Young and Old Donors

Cited by 140 publications

References 0 publications

Cell intrinsic alterations underlie hematopoietic stem cell aging

Cell intrinsic alterations underlie hematopoietic stem cell aging

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

The hematopoietic stroma

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