Cyclophosphamide/granulocyte colony-stimulating factor induces hematopoietic stem cells to proliferate prior to mobilization

Sean J. Morrison, Douglas E. Wright, Irving L. Weissman

Research output: Contribution to journalArticle

228 Citations (Scopus)

Abstract

We isolated hematopoietic stem cells (HSC) from mice treated with cyclophosphamide (CY) and granulocyte colony-stimulating factor (G-CSF). All mobilized multipotent progenitor activity was contained in two populations: Thy-1(lo)Sca-1+Lin-Mac-1-CD4-c-kit+ long-term reconstituting progenitors and Thy-1(lo)Sca-1+Lin-Mac-1(lo)CD4- transiently reconstituting progenitors. CY/G-CSF treatment drove both long-term and transient multipotent progenitors into cycle, leading to a more than 12-fold expansion in the number of long-term self-renewing HSC prior to mobilization. After CY and 2 days of G-CSF treatment the number of bone marrow HSC began to decline and the number of blood and splenic HSC increased. HSC continued to proliferate in the bone marrow and spleen through 8 days of G-CSF treatment, but HSC released into the blood tended to be in G0/G1 phase. Mobilized multipotent progenitors isolated from the spleen were less efficient than normal bone marrow multipotent progenitors in engrafting irradiated mice but did not differ in colony forming unit-spleen (CFU-S) activity or single cell in vitro assays of primitive progenitor activity. The data suggest that mobilized HSC isolated from the spleen are less efficient at homing to and engrafting the bone marrow of irradiated recipient mice.

Original languageEnglish (US)
Pages (from-to)1908-1913
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume94
Issue number5
DOIs
StatePublished - Mar 4 1997

Fingerprint

Granulocyte Colony-Stimulating Factor
Hematopoietic Stem Cells
Cyclophosphamide
Spleen
Bone Marrow
Cell Cycle Resting Phase
G1 Phase
Stem Cells
Population

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

@article{326688aece13430cabef42a8f4afdcf9,
title = "Cyclophosphamide/granulocyte colony-stimulating factor induces hematopoietic stem cells to proliferate prior to mobilization",
abstract = "We isolated hematopoietic stem cells (HSC) from mice treated with cyclophosphamide (CY) and granulocyte colony-stimulating factor (G-CSF). All mobilized multipotent progenitor activity was contained in two populations: Thy-1(lo)Sca-1+Lin-Mac-1-CD4-c-kit+ long-term reconstituting progenitors and Thy-1(lo)Sca-1+Lin-Mac-1(lo)CD4- transiently reconstituting progenitors. CY/G-CSF treatment drove both long-term and transient multipotent progenitors into cycle, leading to a more than 12-fold expansion in the number of long-term self-renewing HSC prior to mobilization. After CY and 2 days of G-CSF treatment the number of bone marrow HSC began to decline and the number of blood and splenic HSC increased. HSC continued to proliferate in the bone marrow and spleen through 8 days of G-CSF treatment, but HSC released into the blood tended to be in G0/G1 phase. Mobilized multipotent progenitors isolated from the spleen were less efficient than normal bone marrow multipotent progenitors in engrafting irradiated mice but did not differ in colony forming unit-spleen (CFU-S) activity or single cell in vitro assays of primitive progenitor activity. The data suggest that mobilized HSC isolated from the spleen are less efficient at homing to and engrafting the bone marrow of irradiated recipient mice.",
author = "Morrison, {Sean J.} and Wright, {Douglas E.} and Weissman, {Irving L.}",
year = "1997",
month = "3",
day = "4",
doi = "10.1073/pnas.94.5.1908",
language = "English (US)",
volume = "94",
pages = "1908--1913",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "5",

}

TY - JOUR

T1 - Cyclophosphamide/granulocyte colony-stimulating factor induces hematopoietic stem cells to proliferate prior to mobilization

AU - Morrison, Sean J.

AU - Wright, Douglas E.

AU - Weissman, Irving L.

PY - 1997/3/4

Y1 - 1997/3/4

N2 - We isolated hematopoietic stem cells (HSC) from mice treated with cyclophosphamide (CY) and granulocyte colony-stimulating factor (G-CSF). All mobilized multipotent progenitor activity was contained in two populations: Thy-1(lo)Sca-1+Lin-Mac-1-CD4-c-kit+ long-term reconstituting progenitors and Thy-1(lo)Sca-1+Lin-Mac-1(lo)CD4- transiently reconstituting progenitors. CY/G-CSF treatment drove both long-term and transient multipotent progenitors into cycle, leading to a more than 12-fold expansion in the number of long-term self-renewing HSC prior to mobilization. After CY and 2 days of G-CSF treatment the number of bone marrow HSC began to decline and the number of blood and splenic HSC increased. HSC continued to proliferate in the bone marrow and spleen through 8 days of G-CSF treatment, but HSC released into the blood tended to be in G0/G1 phase. Mobilized multipotent progenitors isolated from the spleen were less efficient than normal bone marrow multipotent progenitors in engrafting irradiated mice but did not differ in colony forming unit-spleen (CFU-S) activity or single cell in vitro assays of primitive progenitor activity. The data suggest that mobilized HSC isolated from the spleen are less efficient at homing to and engrafting the bone marrow of irradiated recipient mice.

AB - We isolated hematopoietic stem cells (HSC) from mice treated with cyclophosphamide (CY) and granulocyte colony-stimulating factor (G-CSF). All mobilized multipotent progenitor activity was contained in two populations: Thy-1(lo)Sca-1+Lin-Mac-1-CD4-c-kit+ long-term reconstituting progenitors and Thy-1(lo)Sca-1+Lin-Mac-1(lo)CD4- transiently reconstituting progenitors. CY/G-CSF treatment drove both long-term and transient multipotent progenitors into cycle, leading to a more than 12-fold expansion in the number of long-term self-renewing HSC prior to mobilization. After CY and 2 days of G-CSF treatment the number of bone marrow HSC began to decline and the number of blood and splenic HSC increased. HSC continued to proliferate in the bone marrow and spleen through 8 days of G-CSF treatment, but HSC released into the blood tended to be in G0/G1 phase. Mobilized multipotent progenitors isolated from the spleen were less efficient than normal bone marrow multipotent progenitors in engrafting irradiated mice but did not differ in colony forming unit-spleen (CFU-S) activity or single cell in vitro assays of primitive progenitor activity. The data suggest that mobilized HSC isolated from the spleen are less efficient at homing to and engrafting the bone marrow of irradiated recipient mice.

UR - http://www.scopus.com/inward/record.url?scp=0031059252&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031059252&partnerID=8YFLogxK

U2 - 10.1073/pnas.94.5.1908

DO - 10.1073/pnas.94.5.1908

M3 - Article

VL - 94

SP - 1908

EP - 1913

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 5

ER -