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Niche recycling through division-independent egress of hematopoietic stem cells.

Bhattacharya D, Czechowicz A, Ooi AG, Rossi DJ, Bryder D, Weissman IL - J. Exp. Med. (2009)

Bottom Line: Hematopoietic stem cells (HSCs) are thought to reside in discrete niches through stable adhesion, yet previous studies have suggested that host HSCs can be replaced by transplanted donor HSCs, even in the absence of cytoreductive conditioning.Bromodeoxyuridine (BrdU) feeding experiments demonstrated that HSCs in the peripheral blood incorporate BrdU at the same rate as do HSCs in the bone marrow, suggesting that egress from the bone marrow to the blood can occur without cell division and can leave behind vacant HSC niches.These data provide insight as to how HSC replacement can occur despite the residence of endogenous HSCs in niches, and suggest therapeutic interventions that capitalize upon physiological HSC egress.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Stem Cell Biology and Regenerative Medicine Stanford University School of Medicine Stanford, CA 94305, USA. deeptab@wustl.edu

ABSTRACT
Hematopoietic stem cells (HSCs) are thought to reside in discrete niches through stable adhesion, yet previous studies have suggested that host HSCs can be replaced by transplanted donor HSCs, even in the absence of cytoreductive conditioning. To explain this apparent paradox, we calculated, through cell surface phenotyping and transplantation of unfractionated blood, that approximately 1-5% of the total pool of HSCs enters into the circulation each day. Bromodeoxyuridine (BrdU) feeding experiments demonstrated that HSCs in the peripheral blood incorporate BrdU at the same rate as do HSCs in the bone marrow, suggesting that egress from the bone marrow to the blood can occur without cell division and can leave behind vacant HSC niches. Consistent with this, repetitive daily transplantations of small numbers of HSCs administered as new niches became available over the course of 7 d led to significantly higher levels of engraftment than did large, single-bolus transplantations of the same total number of HSCs. These data provide insight as to how HSC replacement can occur despite the residence of endogenous HSCs in niches, and suggest therapeutic interventions that capitalize upon physiological HSC egress.

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HSC egress is either division dependent or independent. HSCs can either undergo an extrinsically asymmetric division, in which one daughter cell is positioned away from a supportive niche and can thus intravasate to the blood (A) or can exit the supportive niche in the absence of cellular division (B). In the former model, all HSCs in the blood would be expected to have incorporated BrdU (gray shaded cells) after an appropriate feeding period, while the latter model would predict similar low BrdU incorporation rates between bone marrow and blood HSCs.
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fig1: HSC egress is either division dependent or independent. HSCs can either undergo an extrinsically asymmetric division, in which one daughter cell is positioned away from a supportive niche and can thus intravasate to the blood (A) or can exit the supportive niche in the absence of cellular division (B). In the former model, all HSCs in the blood would be expected to have incorporated BrdU (gray shaded cells) after an appropriate feeding period, while the latter model would predict similar low BrdU incorporation rates between bone marrow and blood HSCs.

Mentions: Several theoretical mechanisms exist that could describe the source of HSCs in the blood. The first involves an asymmetric division in which after mitosis, one daughter HSC remains positioned within the supportive niche, while the other daughter cell is displaced away (Fig. 1 A). The daughter cell that is displaced can then intravasate into the bloodstream. Another mechanism involves division-independent egress in which an HSC exits its supportive niche in the absence of mitosis, thus leaving behind a vacant HSC niche (Fig. 1 B).


Niche recycling through division-independent egress of hematopoietic stem cells.

Bhattacharya D, Czechowicz A, Ooi AG, Rossi DJ, Bryder D, Weissman IL - J. Exp. Med. (2009)

HSC egress is either division dependent or independent. HSCs can either undergo an extrinsically asymmetric division, in which one daughter cell is positioned away from a supportive niche and can thus intravasate to the blood (A) or can exit the supportive niche in the absence of cellular division (B). In the former model, all HSCs in the blood would be expected to have incorporated BrdU (gray shaded cells) after an appropriate feeding period, while the latter model would predict similar low BrdU incorporation rates between bone marrow and blood HSCs.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC2806613&req=5

fig1: HSC egress is either division dependent or independent. HSCs can either undergo an extrinsically asymmetric division, in which one daughter cell is positioned away from a supportive niche and can thus intravasate to the blood (A) or can exit the supportive niche in the absence of cellular division (B). In the former model, all HSCs in the blood would be expected to have incorporated BrdU (gray shaded cells) after an appropriate feeding period, while the latter model would predict similar low BrdU incorporation rates between bone marrow and blood HSCs.
Mentions: Several theoretical mechanisms exist that could describe the source of HSCs in the blood. The first involves an asymmetric division in which after mitosis, one daughter HSC remains positioned within the supportive niche, while the other daughter cell is displaced away (Fig. 1 A). The daughter cell that is displaced can then intravasate into the bloodstream. Another mechanism involves division-independent egress in which an HSC exits its supportive niche in the absence of mitosis, thus leaving behind a vacant HSC niche (Fig. 1 B).

Bottom Line: Hematopoietic stem cells (HSCs) are thought to reside in discrete niches through stable adhesion, yet previous studies have suggested that host HSCs can be replaced by transplanted donor HSCs, even in the absence of cytoreductive conditioning.Bromodeoxyuridine (BrdU) feeding experiments demonstrated that HSCs in the peripheral blood incorporate BrdU at the same rate as do HSCs in the bone marrow, suggesting that egress from the bone marrow to the blood can occur without cell division and can leave behind vacant HSC niches.These data provide insight as to how HSC replacement can occur despite the residence of endogenous HSCs in niches, and suggest therapeutic interventions that capitalize upon physiological HSC egress.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Stem Cell Biology and Regenerative Medicine Stanford University School of Medicine Stanford, CA 94305, USA. deeptab@wustl.edu

ABSTRACT
Hematopoietic stem cells (HSCs) are thought to reside in discrete niches through stable adhesion, yet previous studies have suggested that host HSCs can be replaced by transplanted donor HSCs, even in the absence of cytoreductive conditioning. To explain this apparent paradox, we calculated, through cell surface phenotyping and transplantation of unfractionated blood, that approximately 1-5% of the total pool of HSCs enters into the circulation each day. Bromodeoxyuridine (BrdU) feeding experiments demonstrated that HSCs in the peripheral blood incorporate BrdU at the same rate as do HSCs in the bone marrow, suggesting that egress from the bone marrow to the blood can occur without cell division and can leave behind vacant HSC niches. Consistent with this, repetitive daily transplantations of small numbers of HSCs administered as new niches became available over the course of 7 d led to significantly higher levels of engraftment than did large, single-bolus transplantations of the same total number of HSCs. These data provide insight as to how HSC replacement can occur despite the residence of endogenous HSCs in niches, and suggest therapeutic interventions that capitalize upon physiological HSC egress.

Show MeSH
Related in: MedlinePlus