Thrombopoietin promotes the survival of murine hematopoietic long-term reconstituting cells: Comparison with the effects of FLT3/FLK-2 ligand and interleukin-6

Takuya Matsunaga, Takashi Kato, Hiroshi Miyazaki, Makio Ogawa

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

The effects of thrombopoietin (TPO; c-mpl ligand), FLT3/FLK-2 ligand (FL), and interleukin-6 (IL-6) on the survival of murine hematopoietic long- term reconstituting cells (LTRC) were studied by using lineage-negative, Sca- 1-positive, c-kit-positive (Lin-Sca-1+c-kit+) marrow cells from 5- fluorouracil-treated mice. We tested the ability of these cytokines to maintain the viability of LTRC by transplanting the cultured cells to lethally irradiated Ly-5 congenic mice together with compromised marrow cells. As a single agent, only TPO could maintain the LTRC. Neither IL-6 nor FL was effective by itself, but they acted synergistically to maintain the LTRC. We examined whether the maintenance of LTRC by these cytokines was due to the survival of stem cells or was the result of active cell divisions and self-renewal. To monitor cell division, we used membrane dye PKH26. Enriched cells were stained with PKH26 on day 0 and incubated in suspension culture with TPO or with IL-6 and FL for 7 days. On day 7, PKH26(low) and PKH26(high) cells were prepared by sorting and their in vivo reconstituting abilities were tested by transplantation into lethally irradiated Ly-5 congenic mice together with compromised marrow cells. PKH26(high) populations cultured with both TPO alone and the combination of IL-6 and FL showed greater reconstitution activity than that of PKH26(low) populations. These data indicate that TPO alone and the combination of IL-6 and FL can support the survival of stem cells without stimulating their active cell proliferation.

Original languageEnglish
Pages (from-to)452-461
Number of pages10
JournalBlood
Volume92
Issue number2
Publication statusPublished - 1998 Jul 15
Externally publishedYes

Fingerprint

Thrombopoietin
Interleukin-6
Cells
Ligands
Stem cells
Congenic Mice
Cytokines
Bone Marrow
Cell Division
Cell proliferation
Sorting
Fluorouracil
Stem Cells
PKH 26
Suspensions
Coloring Agents
Membranes
Population
Cultured Cells
Transplantation

ASJC Scopus subject areas

  • Hematology

Cite this

Thrombopoietin promotes the survival of murine hematopoietic long-term reconstituting cells : Comparison with the effects of FLT3/FLK-2 ligand and interleukin-6. / Matsunaga, Takuya; Kato, Takashi; Miyazaki, Hiroshi; Ogawa, Makio.

In: Blood, Vol. 92, No. 2, 15.07.1998, p. 452-461.

Research output: Contribution to journalArticle

@article{1100d84ed70545b7b5ea381c411deb85,
title = "Thrombopoietin promotes the survival of murine hematopoietic long-term reconstituting cells: Comparison with the effects of FLT3/FLK-2 ligand and interleukin-6",
abstract = "The effects of thrombopoietin (TPO; c-mpl ligand), FLT3/FLK-2 ligand (FL), and interleukin-6 (IL-6) on the survival of murine hematopoietic long- term reconstituting cells (LTRC) were studied by using lineage-negative, Sca- 1-positive, c-kit-positive (Lin-Sca-1+c-kit+) marrow cells from 5- fluorouracil-treated mice. We tested the ability of these cytokines to maintain the viability of LTRC by transplanting the cultured cells to lethally irradiated Ly-5 congenic mice together with compromised marrow cells. As a single agent, only TPO could maintain the LTRC. Neither IL-6 nor FL was effective by itself, but they acted synergistically to maintain the LTRC. We examined whether the maintenance of LTRC by these cytokines was due to the survival of stem cells or was the result of active cell divisions and self-renewal. To monitor cell division, we used membrane dye PKH26. Enriched cells were stained with PKH26 on day 0 and incubated in suspension culture with TPO or with IL-6 and FL for 7 days. On day 7, PKH26(low) and PKH26(high) cells were prepared by sorting and their in vivo reconstituting abilities were tested by transplantation into lethally irradiated Ly-5 congenic mice together with compromised marrow cells. PKH26(high) populations cultured with both TPO alone and the combination of IL-6 and FL showed greater reconstitution activity than that of PKH26(low) populations. These data indicate that TPO alone and the combination of IL-6 and FL can support the survival of stem cells without stimulating their active cell proliferation.",
author = "Takuya Matsunaga and Takashi Kato and Hiroshi Miyazaki and Makio Ogawa",
year = "1998",
month = "7",
day = "15",
language = "English",
volume = "92",
pages = "452--461",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "2",

}

TY - JOUR

T1 - Thrombopoietin promotes the survival of murine hematopoietic long-term reconstituting cells

T2 - Comparison with the effects of FLT3/FLK-2 ligand and interleukin-6

AU - Matsunaga, Takuya

AU - Kato, Takashi

AU - Miyazaki, Hiroshi

AU - Ogawa, Makio

PY - 1998/7/15

Y1 - 1998/7/15

N2 - The effects of thrombopoietin (TPO; c-mpl ligand), FLT3/FLK-2 ligand (FL), and interleukin-6 (IL-6) on the survival of murine hematopoietic long- term reconstituting cells (LTRC) were studied by using lineage-negative, Sca- 1-positive, c-kit-positive (Lin-Sca-1+c-kit+) marrow cells from 5- fluorouracil-treated mice. We tested the ability of these cytokines to maintain the viability of LTRC by transplanting the cultured cells to lethally irradiated Ly-5 congenic mice together with compromised marrow cells. As a single agent, only TPO could maintain the LTRC. Neither IL-6 nor FL was effective by itself, but they acted synergistically to maintain the LTRC. We examined whether the maintenance of LTRC by these cytokines was due to the survival of stem cells or was the result of active cell divisions and self-renewal. To monitor cell division, we used membrane dye PKH26. Enriched cells were stained with PKH26 on day 0 and incubated in suspension culture with TPO or with IL-6 and FL for 7 days. On day 7, PKH26(low) and PKH26(high) cells were prepared by sorting and their in vivo reconstituting abilities were tested by transplantation into lethally irradiated Ly-5 congenic mice together with compromised marrow cells. PKH26(high) populations cultured with both TPO alone and the combination of IL-6 and FL showed greater reconstitution activity than that of PKH26(low) populations. These data indicate that TPO alone and the combination of IL-6 and FL can support the survival of stem cells without stimulating their active cell proliferation.

AB - The effects of thrombopoietin (TPO; c-mpl ligand), FLT3/FLK-2 ligand (FL), and interleukin-6 (IL-6) on the survival of murine hematopoietic long- term reconstituting cells (LTRC) were studied by using lineage-negative, Sca- 1-positive, c-kit-positive (Lin-Sca-1+c-kit+) marrow cells from 5- fluorouracil-treated mice. We tested the ability of these cytokines to maintain the viability of LTRC by transplanting the cultured cells to lethally irradiated Ly-5 congenic mice together with compromised marrow cells. As a single agent, only TPO could maintain the LTRC. Neither IL-6 nor FL was effective by itself, but they acted synergistically to maintain the LTRC. We examined whether the maintenance of LTRC by these cytokines was due to the survival of stem cells or was the result of active cell divisions and self-renewal. To monitor cell division, we used membrane dye PKH26. Enriched cells were stained with PKH26 on day 0 and incubated in suspension culture with TPO or with IL-6 and FL for 7 days. On day 7, PKH26(low) and PKH26(high) cells were prepared by sorting and their in vivo reconstituting abilities were tested by transplantation into lethally irradiated Ly-5 congenic mice together with compromised marrow cells. PKH26(high) populations cultured with both TPO alone and the combination of IL-6 and FL showed greater reconstitution activity than that of PKH26(low) populations. These data indicate that TPO alone and the combination of IL-6 and FL can support the survival of stem cells without stimulating their active cell proliferation.

UR - http://www.scopus.com/inward/record.url?scp=0032528504&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032528504&partnerID=8YFLogxK

M3 - Article

C2 - 9657744

AN - SCOPUS:0032528504

VL - 92

SP - 452

EP - 461

JO - Blood

JF - Blood

SN - 0006-4971

IS - 2

ER -