Suppressive effects of TNF-α, TGF-β1, and chemokines on megakaryocytic colony formation in CD34+ cells derived from umbilical cord blood compared with mobilized peripheral blood and bone marrow

L. Lu, Li Sheng Wang, Ryan J. Cooper, Hong Jun Liu, Katherine Turner, Nadine Weich, Hal Broxmeyer

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

CD34+ cells from human umbilical cord blood (CB) were isolated and investigated for megakaryocytic (MK) colony formation in response to recombinant human (rh) stimulatory and suppressive cytokines and compared with their counterparts in normal BM and G-CSF-mobilized peripheral blood (mPBL). First, we observed that IL-11 by itself at any dosage had no stimulator activity on MK colony formation derived from CD34+ cells in CB, mPBL, and BM. IL-3, steel factor (SLF), or thrombopoietin (Tpo) alone stimulated numbers of colony-forming unit-megakaryocyte (CFU-MK) in a dose- dependent fashion. Maximum growth of MK progenitor cells was noted in the presence of a combination of cytokines: IL-11, IL-3, SLF, and Tpo. The frequency of CFU-MK in CB and mPBL was significantly greater than that in BM, and the size of colonies in CB and mPBL was significantly greater than that in BM, and the size of colonies was larger as well. In addition, an increased number of big mixed colonies containing MK were observed in CB and mPBL. In the presence of IL-11, IL-3, SLF, and Tpo, CFU-MK derived from CB, mPBL, and BM was suppressed by tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1). CFU-MK derived from normal BM was inhibited by some chemokines evaluated, whereas CFU-MK derived from CB was suppressed only by platelet factor-4 (PF-4), IFN-inducible protein-10 (IP-10), Exodus-1, Exodus-2, and Exodus-3, but to a lesser degree. In CB, unlike granulocyte- macrophage (CFU-GM), erythroid (BFU-E), high-proliferative potential (HPP- CFC), or multipotential (CFU-GEMM) progenitors, at least a subpopulation of MK progenitors are in S-phase. Therefore, CB MK progenitors respond to the suppressive effects of some members of the chemokine family. Similar results were noted for burst-forming unit-MK (BFU-MK). Our results indicate that CB and mPBL are rich sources of MK progenitors and that MK progenitors in CB are responsive to the suppressive effects of TNF-α and TGF-β1 and some members of the chemokine family.

Original languageEnglish
Pages (from-to)195-204
Number of pages10
JournalJournal of Hematotherapy and Stem Cell Research
Volume9
Issue number2
DOIs
StatePublished - 2000

Fingerprint

Transforming Growth Factors
Fetal Blood
Chemokines
Tumor Necrosis Factor-alpha
Bone Marrow
Megakaryocytes
Stem Cells
Interleukin-11
Thrombopoietin
Stem Cell Factor
Interleukin-3
Cytokines
Myeloid Progenitor Cells
Platelet Factor 4
Granulocyte-Macrophage Progenitor Cells
Erythroid Precursor Cells
Granulocyte Colony-Stimulating Factor
S Phase
Granulocytes
Macrophages

ASJC Scopus subject areas

  • Hematology
  • Immunology

Cite this

Suppressive effects of TNF-α, TGF-β1, and chemokines on megakaryocytic colony formation in CD34+ cells derived from umbilical cord blood compared with mobilized peripheral blood and bone marrow. / Lu, L.; Wang, Li Sheng; Cooper, Ryan J.; Liu, Hong Jun; Turner, Katherine; Weich, Nadine; Broxmeyer, Hal.

In: Journal of Hematotherapy and Stem Cell Research, Vol. 9, No. 2, 2000, p. 195-204.

Research output: Contribution to journalArticle

@article{1185b52525b54b54adbfd846ad926ed9,
title = "Suppressive effects of TNF-α, TGF-β1, and chemokines on megakaryocytic colony formation in CD34+ cells derived from umbilical cord blood compared with mobilized peripheral blood and bone marrow",
abstract = "CD34+ cells from human umbilical cord blood (CB) were isolated and investigated for megakaryocytic (MK) colony formation in response to recombinant human (rh) stimulatory and suppressive cytokines and compared with their counterparts in normal BM and G-CSF-mobilized peripheral blood (mPBL). First, we observed that IL-11 by itself at any dosage had no stimulator activity on MK colony formation derived from CD34+ cells in CB, mPBL, and BM. IL-3, steel factor (SLF), or thrombopoietin (Tpo) alone stimulated numbers of colony-forming unit-megakaryocyte (CFU-MK) in a dose- dependent fashion. Maximum growth of MK progenitor cells was noted in the presence of a combination of cytokines: IL-11, IL-3, SLF, and Tpo. The frequency of CFU-MK in CB and mPBL was significantly greater than that in BM, and the size of colonies in CB and mPBL was significantly greater than that in BM, and the size of colonies was larger as well. In addition, an increased number of big mixed colonies containing MK were observed in CB and mPBL. In the presence of IL-11, IL-3, SLF, and Tpo, CFU-MK derived from CB, mPBL, and BM was suppressed by tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1). CFU-MK derived from normal BM was inhibited by some chemokines evaluated, whereas CFU-MK derived from CB was suppressed only by platelet factor-4 (PF-4), IFN-inducible protein-10 (IP-10), Exodus-1, Exodus-2, and Exodus-3, but to a lesser degree. In CB, unlike granulocyte- macrophage (CFU-GM), erythroid (BFU-E), high-proliferative potential (HPP- CFC), or multipotential (CFU-GEMM) progenitors, at least a subpopulation of MK progenitors are in S-phase. Therefore, CB MK progenitors respond to the suppressive effects of some members of the chemokine family. Similar results were noted for burst-forming unit-MK (BFU-MK). Our results indicate that CB and mPBL are rich sources of MK progenitors and that MK progenitors in CB are responsive to the suppressive effects of TNF-α and TGF-β1 and some members of the chemokine family.",
author = "L. Lu and Wang, {Li Sheng} and Cooper, {Ryan J.} and Liu, {Hong Jun} and Katherine Turner and Nadine Weich and Hal Broxmeyer",
year = "2000",
doi = "10.1089/152581600319405",
language = "English",
volume = "9",
pages = "195--204",
journal = "Stem Cells and Development",
issn = "1547-3287",
publisher = "Mary Ann Liebert Inc.",
number = "2",

}

TY - JOUR

T1 - Suppressive effects of TNF-α, TGF-β1, and chemokines on megakaryocytic colony formation in CD34+ cells derived from umbilical cord blood compared with mobilized peripheral blood and bone marrow

AU - Lu, L.

AU - Wang, Li Sheng

AU - Cooper, Ryan J.

AU - Liu, Hong Jun

AU - Turner, Katherine

AU - Weich, Nadine

AU - Broxmeyer, Hal

PY - 2000

Y1 - 2000

N2 - CD34+ cells from human umbilical cord blood (CB) were isolated and investigated for megakaryocytic (MK) colony formation in response to recombinant human (rh) stimulatory and suppressive cytokines and compared with their counterparts in normal BM and G-CSF-mobilized peripheral blood (mPBL). First, we observed that IL-11 by itself at any dosage had no stimulator activity on MK colony formation derived from CD34+ cells in CB, mPBL, and BM. IL-3, steel factor (SLF), or thrombopoietin (Tpo) alone stimulated numbers of colony-forming unit-megakaryocyte (CFU-MK) in a dose- dependent fashion. Maximum growth of MK progenitor cells was noted in the presence of a combination of cytokines: IL-11, IL-3, SLF, and Tpo. The frequency of CFU-MK in CB and mPBL was significantly greater than that in BM, and the size of colonies in CB and mPBL was significantly greater than that in BM, and the size of colonies was larger as well. In addition, an increased number of big mixed colonies containing MK were observed in CB and mPBL. In the presence of IL-11, IL-3, SLF, and Tpo, CFU-MK derived from CB, mPBL, and BM was suppressed by tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1). CFU-MK derived from normal BM was inhibited by some chemokines evaluated, whereas CFU-MK derived from CB was suppressed only by platelet factor-4 (PF-4), IFN-inducible protein-10 (IP-10), Exodus-1, Exodus-2, and Exodus-3, but to a lesser degree. In CB, unlike granulocyte- macrophage (CFU-GM), erythroid (BFU-E), high-proliferative potential (HPP- CFC), or multipotential (CFU-GEMM) progenitors, at least a subpopulation of MK progenitors are in S-phase. Therefore, CB MK progenitors respond to the suppressive effects of some members of the chemokine family. Similar results were noted for burst-forming unit-MK (BFU-MK). Our results indicate that CB and mPBL are rich sources of MK progenitors and that MK progenitors in CB are responsive to the suppressive effects of TNF-α and TGF-β1 and some members of the chemokine family.

AB - CD34+ cells from human umbilical cord blood (CB) were isolated and investigated for megakaryocytic (MK) colony formation in response to recombinant human (rh) stimulatory and suppressive cytokines and compared with their counterparts in normal BM and G-CSF-mobilized peripheral blood (mPBL). First, we observed that IL-11 by itself at any dosage had no stimulator activity on MK colony formation derived from CD34+ cells in CB, mPBL, and BM. IL-3, steel factor (SLF), or thrombopoietin (Tpo) alone stimulated numbers of colony-forming unit-megakaryocyte (CFU-MK) in a dose- dependent fashion. Maximum growth of MK progenitor cells was noted in the presence of a combination of cytokines: IL-11, IL-3, SLF, and Tpo. The frequency of CFU-MK in CB and mPBL was significantly greater than that in BM, and the size of colonies in CB and mPBL was significantly greater than that in BM, and the size of colonies was larger as well. In addition, an increased number of big mixed colonies containing MK were observed in CB and mPBL. In the presence of IL-11, IL-3, SLF, and Tpo, CFU-MK derived from CB, mPBL, and BM was suppressed by tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1). CFU-MK derived from normal BM was inhibited by some chemokines evaluated, whereas CFU-MK derived from CB was suppressed only by platelet factor-4 (PF-4), IFN-inducible protein-10 (IP-10), Exodus-1, Exodus-2, and Exodus-3, but to a lesser degree. In CB, unlike granulocyte- macrophage (CFU-GM), erythroid (BFU-E), high-proliferative potential (HPP- CFC), or multipotential (CFU-GEMM) progenitors, at least a subpopulation of MK progenitors are in S-phase. Therefore, CB MK progenitors respond to the suppressive effects of some members of the chemokine family. Similar results were noted for burst-forming unit-MK (BFU-MK). Our results indicate that CB and mPBL are rich sources of MK progenitors and that MK progenitors in CB are responsive to the suppressive effects of TNF-α and TGF-β1 and some members of the chemokine family.

UR - http://www.scopus.com/inward/record.url?scp=0034069029&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034069029&partnerID=8YFLogxK

U2 - 10.1089/152581600319405

DO - 10.1089/152581600319405

M3 - Article

C2 - 10813532

AN - SCOPUS:0034069029

VL - 9

SP - 195

EP - 204

JO - Stem Cells and Development

JF - Stem Cells and Development

SN - 1547-3287

IS - 2

ER -