Some Properties of the Circulating Hemopoietic Stem Cells

Gidáli, J; Fehér, I.; Antal, Sára

doi:10.1182/blood.v43.4.573.573

Cited by 40 publications

(4 citation statements)

References 24 publications

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“…Although our data argue against a direct effect of the cycling status of CFU on their capacity for self-renewal, it is probable that rapid cell cycle is related to poor self-renewal in the reverse way: strongly self-renewing stem cells appear to enter cycle rarely, whereas those that self-renew less cycle relatively often (29,34).…”

Section: Discussioncontrasting

confidence: 56%

Serial depletion and regeneration of the murine hematopoietic system. Implications for hematopoietic organization and the study of cellular aging

Ross¹,

Anderson²,

Micklem³

1982

The Journal of Experimental Medicine

123

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The mouse hematopoietic system was subjected to repeated depletion and regeneration either by serial transfer of bone marrow cells through lethally irradiated recipients or by repeated treatment with the cycle-active drug hydroxyurea (HU). The capacity of surviving stem cells to proliferate and self-renew was assayed at intervals by two methods: (a) the spleen colony method; and (b) competitive repopulation of irradiated recipients using chromosome markers, with normal bone marrow cells as an internal control. The progressive decline in stem cell function that occurred during serial transfer of bone marrow and that had already begun after a single transfer was not seen during HU treatment; up to 25 pairs of HU injections given over more than 1 yr had no discernible effect on the number of stem cells present 3 wk after the final injection or on their capacity to self-renew. Within 2 d after exposure to HU, the average self-renewal capacity of surviving stem cells was enhanced. This implies that the drug selectively eliminates poorly self-renewing stem cells and hence that these enter cycle more readily than stem cells with a high self-replicative potential. However, the fact of being in cycle at the time of injection did not of itself affect self-renewal. The results show that serial transfer of bone marrow is not a valid method for studying clonal aging phenomena because it does not fulfill the assumptions on which such studies are based. No evidence was obtained for any intrinsic limitation in the capacity of bone marrow populations for repeated regeneration after HU-induced depletion. However, this does not necessarily imply that individual hematopoietic clones are capable of indefinite expansion because hematopoiesis may (as suggested by the relative resistance of highly self-replicative stem cells to mitogenic signals) proceed on the basis of clonal succession.

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Section: Discussioncontrasting

confidence: 56%

Serial depletion and regeneration of the murine hematopoietic system. Implications for hematopoietic organization and the study of cellular aging

Ross¹,

Anderson²,

Micklem³

1982

The Journal of Experimental Medicine

123

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“…Moreover, several data suggest that CFU-S in blood result from a selection process. Circulating CFU-S would be in cycle (as opposed to marrow CFU-S) [96]; they would be less radiosensitive than marrow CFU-S [96]. Eventually the self-renewal capacity and the repopulating ability of circulating stem cells would be less than that of marrow cells [97].…”

Section: Circulating Stem Cells Under Stationary Conditionsmentioning

confidence: 99%

Hemopoietic stem cells: Analysis of some parameters critical for engraftment

Charbord

1994

STEM CELLS

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In this review four parameters relevant to the grafting of hemopoietic stem cells (HSC) are analyzed: the nature and amounts of grafted HSC, the sources of HSC and the "in vivo" fate of the grafted cells. One may oppose cells with short-term repopulating ability to cells with long-term reconstitutive capacity. The former comprise progenitors, while the latter consist of primitive stem cells, corresponding to murine pre-colony forming units-spleen (pre-CFU-S) (and to some murine CFU-S) or to human pre-colony forming units (pre-CFU). In the mouse, the number of progenitors involved in short-term reconstitution is large, while that of primitive cells operating months after the transplantation is reduced. These results may be extrapolated to humans, suggesting that it is possible to engraft a limited number of genetically modified HSC. However, the administration of large numbers of reconstituting cells appears to be a cautionary procedure, since it should insure polyclonal hemopoiesis, which is the physiological situation in mammals. Besides marrow, peripheral blood from adult patients treated with chemotherapy and growth factors, and cord blood from newborns, are promising sources of HSC. Successful engraftment depends not only on the quality and quantity of HSC, but also on the integrity of the marrow microenvironment. This microenvironment may be impaired by chemo- and radiotherapy, which provides a theoretical basis for the transplantation of stromal cells along with that of HSC.

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“…We determined that bgJ/bg ~ marrow contains 24 -4-3 CFUs per 1@ nucleated cells and that 1.3 _+ 0.4% of the transplanted CFUs could be recovered from the marrow of a W/W v femur 24 h later. When the CFUs concentration is corrected for a seeding efficiency of 10% in the spleen colony assay (15)(16)(17), it follows that injection of 10 ~ bgJ/bg J bone marrow cells led to the delivery of about three CFUs to the marrow in each femur. Because a femur contains 6% of the marrow of a mouse, about 50 CFUs were therefore delivered to the total marrow.…”

Section: Resultsmentioning

confidence: 99%

Hematopoietic stem cell regulatory volumes as revealed in studies of the bgj/bgj:W/WV chimera.

Maloney

Dorie

Lamela

et al. 1978

The Journal of Experimental Medicine

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Foremost among the open questions of hematopoiesis is the nature of the mechanisms that govern the behavior of pluripotent stem cells. Several types of evidence suggest that stem cell activities are directed by local control systems. Local regulation is apparently expressed in the centripetal movement of active marrow during postnatal growth of many species, in the predilection of hematopoietic foci for endosteal surfaces (1), in the selective distribution of erythroid and granuloid colonies arising from stem cells implanted in Xirradiated mice (2), and in the microenvironmental defect seen in genetically anemic mice carrying the mutant steel locus (3, 4). The effects of adherent cells derived from marrow as seen in heterotopic implants (5) and in bone marrow cultures (6) are also strongly suggestive of a regulatory role of bone marrowassociated elements in the activities of pluripotent stem cells. Because the W/W v mouse has very few macrocolony-forming stem cells (CFUs) ~ but an apparently normal marrow microenvironment, this genotype may be useful for studying the interaction between CFUs and their immediate environment. This follows from the comparative ease with which CFUs from +/+ littermates or congenic mouse strains can be transplanted to W/W ~ mice without irradiation or other treatment (7-9). We are concerned here with the evolution of bone marrow chimerism in the W/W v mouse as a function of marrow transplantation dose. The results of this study point to the existence of discrete stem cell regulatory vol of about 10 8 ftm 3, a dimension consistent with concepts of shortrange cell-cell interactions. Materials and MethodsWe chose histocompatible bgJ/bg ~ (beige) mouse marrow as the source of CFUs for the W/W ~ mouse because the giant sudanophilic granules (>1 ~m) characteristic of bgJ/bg j neutrophils provide a convenient marker of W/W ~" marrow replacement (8). W/V~ and bg~/bg J mice were purchased from The Jackson Laboratory, Bar Harbor, Maine. Both male and female bgJ/bg J mice, 2-4 mo of age and weighing 20-25 g, were used as marrow donors, but only male W/W ~ mice of similar age weighing 15--20 g were used as bone marrow recipients because of incompatibility of a male graft in a female host. Donor marrow was obtained from a femur shaft, suspended in Hanks' balanced salt solution for total nucleated cell counts, and then serially diluted with additional Hanks' solution to the desired cell concentrations. Each W/V~" recipient was injected with 0.5 ml of the appropriate bgJ/bg J marrow cell suspension by tail vein.* Supported by the U. S. Department of Energy.1 Abbreviation used in this paper: CFUs, macrocolony-forming stem cells. J. ExP. Mzv.

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Some Properties of the Circulating Hemopoietic Stem Cells

Cited by 40 publications

References 24 publications

Serial depletion and regeneration of the murine hematopoietic system. Implications for hematopoietic organization and the study of cellular aging

Serial depletion and regeneration of the murine hematopoietic system. Implications for hematopoietic organization and the study of cellular aging

Hemopoietic stem cells: Analysis of some parameters critical for engraftment

Hematopoietic stem cell regulatory volumes as revealed in studies of the bgj/bgj:W/WV chimera.

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