Synergistic neovascularization by mixed transplantation of early endothelial progenitor cells and late outgrowth endothelial cells: The role of angiogenic cytokines and matrix metalloproteinases

Chang Hwan Yoon, Jin Hur, Kyung Woo Park, Ji Hyun Kim, Choon Soo Lee, I. Young Oh, Tae Youn Kim, Hyun Jai Cho, Hyun Jae Kang, In Ho Chae, Han Kwang Yang, Byung Hee Oh, Young Bae Park, Hyo Soo Kim

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Abstract

Background - Two types of cells are cultured from the human peripheral blood, early endothelial progenitor cells (EPCs) and outgrowth endothelial cells (OECs), as previously reported. Here, we further characterize these cells, especially with respect to their different origins and functions both in vitro and in vivo. We also investigated whether the combination of these different cell types shows synergism during neovascularization. Methods and Results - Early EPCs were heterogeneously made up of both CD14+ monocyte-derived cells, which secrete cytokines, and CD14--derived cells, which contain high levels of CD34+KDR+ cells. OECs were cultured almost exclusively from CD14- cells, not CD14 + cells, and were distinct from mature endothelial cells in terms of proliferation potential, KDR+ expression level, and telomerase activity. A portion of cells from CD14- cells and early EPCs produced rapidly proliferating, capillary-forming cells in both the Matrigel plug and the ischemic hind limb similar to OECs. Early EPCs and OECs expressed receptors for vascular endothelial growth factor and interleukin-8, cytokines secreted by early EPCs. There was a differential increase in matrix metalloproteinases (MMPs): MMP-9 in early EPCs and MMP-2 in OECs. In vitro, the angiogenic capability of the 2 cell types was augmented by mutual interaction through cytokines and MMPs. Injection of a mixture of the 2 cells resulted in superior neovascularization in vivo to any single-cell-type transplantation. Conclusions - Distinct origins of the different types of EPCs exist that have different functions in neovascularization. Mixed transplantation of these cells results in synergistic neovascularization through cytokines and MMPs.

Original languageEnglish
Pages (from-to)1618-1627
Number of pages10
JournalCirculation
Volume112
Issue number11
DOIs
StatePublished - 13 Sep 2005

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Matrix Metalloproteinases
Endothelial Cells
Transplantation
Cytokines
Cell Transplantation
Endothelial Progenitor Cells
Vascular Endothelial Growth Factor Receptor
Telomerase
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Interleukin-8
Monocytes
Cultured Cells
Extremities
Injections

Keywords

  • Angiogenesis
  • Cells
  • Endothelium
  • Ischemia
  • Revascularization

Cite this

@article{3a1364b0c32d4a739043b77a557e0384,
title = "Synergistic neovascularization by mixed transplantation of early endothelial progenitor cells and late outgrowth endothelial cells: The role of angiogenic cytokines and matrix metalloproteinases",
abstract = "Background - Two types of cells are cultured from the human peripheral blood, early endothelial progenitor cells (EPCs) and outgrowth endothelial cells (OECs), as previously reported. Here, we further characterize these cells, especially with respect to their different origins and functions both in vitro and in vivo. We also investigated whether the combination of these different cell types shows synergism during neovascularization. Methods and Results - Early EPCs were heterogeneously made up of both CD14+ monocyte-derived cells, which secrete cytokines, and CD14--derived cells, which contain high levels of CD34+KDR+ cells. OECs were cultured almost exclusively from CD14- cells, not CD14 + cells, and were distinct from mature endothelial cells in terms of proliferation potential, KDR+ expression level, and telomerase activity. A portion of cells from CD14- cells and early EPCs produced rapidly proliferating, capillary-forming cells in both the Matrigel plug and the ischemic hind limb similar to OECs. Early EPCs and OECs expressed receptors for vascular endothelial growth factor and interleukin-8, cytokines secreted by early EPCs. There was a differential increase in matrix metalloproteinases (MMPs): MMP-9 in early EPCs and MMP-2 in OECs. In vitro, the angiogenic capability of the 2 cell types was augmented by mutual interaction through cytokines and MMPs. Injection of a mixture of the 2 cells resulted in superior neovascularization in vivo to any single-cell-type transplantation. Conclusions - Distinct origins of the different types of EPCs exist that have different functions in neovascularization. Mixed transplantation of these cells results in synergistic neovascularization through cytokines and MMPs.",
keywords = "Angiogenesis, Cells, Endothelium, Ischemia, Revascularization",
author = "Yoon, {Chang Hwan} and Jin Hur and Park, {Kyung Woo} and Kim, {Ji Hyun} and Lee, {Choon Soo} and Oh, {I. Young} and Kim, {Tae Youn} and Cho, {Hyun Jai} and Kang, {Hyun Jae} and Chae, {In Ho} and Yang, {Han Kwang} and Oh, {Byung Hee} and Park, {Young Bae} and Kim, {Hyo Soo}",
year = "2005",
month = "9",
day = "13",
doi = "10.1161/CIRCULATIONAHA.104.503433",
language = "English",
volume = "112",
pages = "1618--1627",
journal = "Circulation",
issn = "0009-7322",
publisher = "Lippincott Williams and Wilkins Ltd.",
number = "11",

}

TY - JOUR

T1 - Synergistic neovascularization by mixed transplantation of early endothelial progenitor cells and late outgrowth endothelial cells

T2 - The role of angiogenic cytokines and matrix metalloproteinases

AU - Yoon, Chang Hwan

AU - Hur, Jin

AU - Park, Kyung Woo

AU - Kim, Ji Hyun

AU - Lee, Choon Soo

AU - Oh, I. Young

AU - Kim, Tae Youn

AU - Cho, Hyun Jai

AU - Kang, Hyun Jae

AU - Chae, In Ho

AU - Yang, Han Kwang

AU - Oh, Byung Hee

AU - Park, Young Bae

AU - Kim, Hyo Soo

PY - 2005/9/13

Y1 - 2005/9/13

N2 - Background - Two types of cells are cultured from the human peripheral blood, early endothelial progenitor cells (EPCs) and outgrowth endothelial cells (OECs), as previously reported. Here, we further characterize these cells, especially with respect to their different origins and functions both in vitro and in vivo. We also investigated whether the combination of these different cell types shows synergism during neovascularization. Methods and Results - Early EPCs were heterogeneously made up of both CD14+ monocyte-derived cells, which secrete cytokines, and CD14--derived cells, which contain high levels of CD34+KDR+ cells. OECs were cultured almost exclusively from CD14- cells, not CD14 + cells, and were distinct from mature endothelial cells in terms of proliferation potential, KDR+ expression level, and telomerase activity. A portion of cells from CD14- cells and early EPCs produced rapidly proliferating, capillary-forming cells in both the Matrigel plug and the ischemic hind limb similar to OECs. Early EPCs and OECs expressed receptors for vascular endothelial growth factor and interleukin-8, cytokines secreted by early EPCs. There was a differential increase in matrix metalloproteinases (MMPs): MMP-9 in early EPCs and MMP-2 in OECs. In vitro, the angiogenic capability of the 2 cell types was augmented by mutual interaction through cytokines and MMPs. Injection of a mixture of the 2 cells resulted in superior neovascularization in vivo to any single-cell-type transplantation. Conclusions - Distinct origins of the different types of EPCs exist that have different functions in neovascularization. Mixed transplantation of these cells results in synergistic neovascularization through cytokines and MMPs.

AB - Background - Two types of cells are cultured from the human peripheral blood, early endothelial progenitor cells (EPCs) and outgrowth endothelial cells (OECs), as previously reported. Here, we further characterize these cells, especially with respect to their different origins and functions both in vitro and in vivo. We also investigated whether the combination of these different cell types shows synergism during neovascularization. Methods and Results - Early EPCs were heterogeneously made up of both CD14+ monocyte-derived cells, which secrete cytokines, and CD14--derived cells, which contain high levels of CD34+KDR+ cells. OECs were cultured almost exclusively from CD14- cells, not CD14 + cells, and were distinct from mature endothelial cells in terms of proliferation potential, KDR+ expression level, and telomerase activity. A portion of cells from CD14- cells and early EPCs produced rapidly proliferating, capillary-forming cells in both the Matrigel plug and the ischemic hind limb similar to OECs. Early EPCs and OECs expressed receptors for vascular endothelial growth factor and interleukin-8, cytokines secreted by early EPCs. There was a differential increase in matrix metalloproteinases (MMPs): MMP-9 in early EPCs and MMP-2 in OECs. In vitro, the angiogenic capability of the 2 cell types was augmented by mutual interaction through cytokines and MMPs. Injection of a mixture of the 2 cells resulted in superior neovascularization in vivo to any single-cell-type transplantation. Conclusions - Distinct origins of the different types of EPCs exist that have different functions in neovascularization. Mixed transplantation of these cells results in synergistic neovascularization through cytokines and MMPs.

KW - Angiogenesis

KW - Cells

KW - Endothelium

KW - Ischemia

KW - Revascularization

UR - http://www.scopus.com/inward/record.url?scp=24944526542&partnerID=8YFLogxK

U2 - 10.1161/CIRCULATIONAHA.104.503433

DO - 10.1161/CIRCULATIONAHA.104.503433

M3 - Article

C2 - 16145003

AN - SCOPUS:24944526542

VL - 112

SP - 1618

EP - 1627

JO - Circulation

JF - Circulation

SN - 0009-7322

IS - 11

ER -