The self renewal probability of hemopoietic stem cells

Vogel, Helmut; Niewisch, Helgard; Matioli, G.T.

doi:10.1002/jcp.1040720309

Cited by 104 publications

(35 citation statements)

References 5 publications

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“…The 5-fold difference in numbers ofcolonies obtained by in vitro and in vivo methods corresponds closely to the assumed seeding efficiency of CFU-S cells (3), thus accounting for the similarity in estimates of self-renewal determined by the two methods-i.e., at least two or three and up to at least five or six self-renewal divisions completed in the first 9 days ofcolony growth. These values are also similar to previous estimates for CFU-S cell self-renewal in 8-to 9-day-old spleen colonies (3,5). It should be noted that macroscopic erythroid colony numbers in assays of fresh marrow account for only 10% of the total CFU-S population, a discrepancy that remains unexplained.…”

Section: Discussionsupporting

confidence: 89%

“…Shortly after the spleen colony assay was described, the observation was made that the number of CFU-S cells present in individual spleen colonies was remarkably variable from one colony to another (3)(4)(5). These results were considered to be at variance with those expected for a homogeneous population of stem cells subject to the same proliferative pressures during spleen colony formation.…”

mentioning

confidence: 99%

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Self-renewal of hemopoietic stem cells during mixed colony formation in vitro.

Humphries¹,

Eaves²,

Eaves³

1981

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

136

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Replating experiments have shown that the selfrenewal of pluripotent hemopoietic stem cells can be studied in vitro by clonal analysis techniques. The number of daughter stem cells detectable in individual primary clones produced in vitro varies markedly from one clone to another. These findings are consistent with a general model of stem cell differentiation in which the choice to self-replicate or not is ultimately determined at the single-cell level by a mechanism involving a random-event component that is intrinsic to the stem cell itself. Hemopoietic stem cells were identified by their ability to generate macroscopic-sized colonies having a visible erythroid component (i.e., gross red color) in standard methylcellulose assays containing medium conditioned by pokeweed mitogen-treated spleen cells and erythropoietin. In assays of replated primary or secondary colonies, inclusion of irradiated marrow-cell feeders was found to be an additional requirement. The mixed erythroid-megakaryocyte-granulocyte nature ofcolonies identified simply as macroscopic and erythroid was confirmed by cytochemical stains for lineage-specific markers. Marked variation in self-renewal was a feature of marrow stem cells both before and after maintenance in flask culture, although the overall self-renewal capacity exhibited by flask-cultured cells was n5-fold higher. Variation in self-renewal was not correlated with primary colony size, which also varied over a wide range (0.2-9 x 105 nucleated cells per colony). Variation in stem cell selfrenewal has been previously associated with hemopoietic stem cell proliferation in vivo. Its persistence in vitro in assays of dilute single-cell suspensions casts doubt on the significance of microenvironmental influences in directing stem cell differentiation.

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Section: Discussionsupporting

confidence: 89%

mentioning

confidence: 99%

Self-renewal of hemopoietic stem cells during mixed colony formation in vitro.

Humphries¹,

Eaves²,

Eaves³

1981

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

136

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“…Sci in which Cn = the number of cells in the limb bone marrow at the time of the next transfer (14 days). Determination of Probability P. This consideration was first described by Till et al (22) and elaborated on by Vogel et al (23). The division of stem cells can be described by using a model with three types of cells: CFU, transition cells, and mature cells.…”

mentioning

confidence: 99%

Proliferative capacity of murine hematopoietic stem cells.

Hellman¹,

Botnick²,

Hannon³

et al. 1978

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

126

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The present study demonstrates a decrease in self-renewal capacity with serial transfer of murine hematopoietic stem cells. Production of differentiated cell progeny is maintained longer than stem cell self-renewal. In normal animals the capacity for self-renewal is not decreased with increasing donor age. The stem cell compartment in normal animals, both young and old, appears to be proliferatively quiescent. After apparent recovery from the alkylating agent busulfan, the probability of stem cell self-renewal is decreased, there is a permanent defect in the capacity of the bone marrow for serial transplantation, and the stem cells are proliferatively active. These findings support a model of the hematopoietic stem cell compartment as a continuum of cells with decreasing capacities for self-renewal, increasing likelihood for differentiation, and increasing proliferative activity. Cells progress in the continuum in one direction and such progression is not reversible.

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“…Support for this model was provided by the similarity of the Gaussian distribution curve of CFU-S per colony to the theoretical distribution generated by Monte Carlo statistics. (Vogel et al 1968(Vogel et al , 1969 and more recently by in vitro studies of stem cell differentiation (Ogawa et al 1983(Ogawa et al , 1989. It has been demonstrated by many workers that proliferative stress provided by serial transplantation significantly reduces self-renewal capacity suggesting that the stem cell compartment may 'age' and thus have a finite lifespan (Schofield 1978) albeit a lifespan well in excess of the normal physiological requirements of the organism.…”

Section: Heterogeneity Of Cfu-s and The Identification Of A Pre-cfu-smentioning

confidence: 99%

Haemopoietic stem cells: their heterogeneity and regulation

Graham

Wright

1997

Int J Experimental Path

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Summary. The maintenance of the various blood cell populations in mammals is achieved by the proliferation and differentiation of precursor cells located primarily in the bone marrow. These precursor cells are all derived from a common haemopoietic stem cell population that is established during embryogenesis and functions for the lifetime of the organism. An overview is given of the various assay systems for haemopoietic stem cells, how these assays have contributed to understanding the considerable heterogeneity within the stem cell compartment, the regulation of stem cells and the development of the haemopoietic system.

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The self renewal probability of hemopoietic stem cells

Cited by 104 publications

References 5 publications

Self-renewal of hemopoietic stem cells during mixed colony formation in vitro.

Self-renewal of hemopoietic stem cells during mixed colony formation in vitro.

Proliferative capacity of murine hematopoietic stem cells.

Haemopoietic stem cells: their heterogeneity and regulation

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