Therapeutic angiogenesis by ex vivo expanded erythroid progenitor cells

Shuji Sasaki, Toyoshi Inoguchi, Koichiro Muta, Yasunobu Abe, Min Zhang, Hiasa Ken-Ichi, Kensuke Egashira, Noriyuki Sonoda, Kunihisa Kobayashi, Ryoichi Takayanagi, Hajime Nawata

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Recent reports have demonstrated that erythroid progenitor cells contain and secrete various angiogenic cytokines. Here, the impact of erythroid colony-forming cell (ECFC) implantation on therapeutic angiogenesis was investigated in murine models of hindlimb ischemia. During the in vitro differentiation, vascular endothelial growth factor (VEGF) secretion by ECFCs was observed from day 3 (burst-forming unit erythroid cells) to day 10 (erythroblasts). ECFCs from day 5 to day 7 (colony-forming unit erythroid cells) showed the highest VEGF productivity, and day 6 ECFCs were used for the experiments. ECFCs contained larger amounts of VEGF and fibroblast growth factor-2 (FGF-2) than peripheral blood mononuclear cells (PBMNCs). In tubule formation assays with human umbilical vein endothelial cells, ECFCs stimulated 1.5-fold more capillary growth than PBMNCs, and this effect was suppressed by antibodies against VEGF and FGF-2. Using an immunodeficient hindlimb ischemia model and laser-Doppler imaging, we evaluated the limb salvage rate and blood perfusion after intramuscular implantation of ECFCs. ECFC implantation increased both the salvage rate (38% vs. 0%, P < 0.05) and the blood perfusion (82.8% vs. 65.6%, P < 0.01). In addition, ECFCs implantation also significantly increased capillaries with recruitment of vascular smooth muscle cells and the capillary density was 1.6-fold higher than in the control group. Continuous production of human VEGF from ECFCs in the skeletal muscle was confirmed at least 7 days after the implantation. Implantation of ECFCs promoted angiogenesis in ischemic limbs by supplying angiogenic cytokines (VEGF and FGF-2), suggesting a possible novel strategy for therapeutic angiogenesis.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume292
Issue number1
DOIs
Publication statusPublished - Jan 1 2007

Fingerprint

Erythroid Precursor Cells
Vascular Endothelial Growth Factor A
Fibroblast Growth Factor 2
Erythroid Cells
Hindlimb
Blood Cells
Ischemia
Perfusion
Cytokines
Therapeutics
Erythroblasts
Limb Salvage
Human Umbilical Vein Endothelial Cells
Vascular Smooth Muscle
Smooth Muscle Myocytes
Skeletal Muscle
Lasers
Stem Cells
Extremities
Cell Count

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Therapeutic angiogenesis by ex vivo expanded erythroid progenitor cells. / Sasaki, Shuji; Inoguchi, Toyoshi; Muta, Koichiro; Abe, Yasunobu; Zhang, Min; Ken-Ichi, Hiasa; Egashira, Kensuke; Sonoda, Noriyuki; Kobayashi, Kunihisa; Takayanagi, Ryoichi; Nawata, Hajime.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 292, No. 1, 01.01.2007.

Research output: Contribution to journalArticle

Sasaki, Shuji ; Inoguchi, Toyoshi ; Muta, Koichiro ; Abe, Yasunobu ; Zhang, Min ; Ken-Ichi, Hiasa ; Egashira, Kensuke ; Sonoda, Noriyuki ; Kobayashi, Kunihisa ; Takayanagi, Ryoichi ; Nawata, Hajime. / Therapeutic angiogenesis by ex vivo expanded erythroid progenitor cells. In: American Journal of Physiology - Heart and Circulatory Physiology. 2007 ; Vol. 292, No. 1.
@article{fdbf7a73a69e400fae60bee2a97f0d9a,
title = "Therapeutic angiogenesis by ex vivo expanded erythroid progenitor cells",
abstract = "Recent reports have demonstrated that erythroid progenitor cells contain and secrete various angiogenic cytokines. Here, the impact of erythroid colony-forming cell (ECFC) implantation on therapeutic angiogenesis was investigated in murine models of hindlimb ischemia. During the in vitro differentiation, vascular endothelial growth factor (VEGF) secretion by ECFCs was observed from day 3 (burst-forming unit erythroid cells) to day 10 (erythroblasts). ECFCs from day 5 to day 7 (colony-forming unit erythroid cells) showed the highest VEGF productivity, and day 6 ECFCs were used for the experiments. ECFCs contained larger amounts of VEGF and fibroblast growth factor-2 (FGF-2) than peripheral blood mononuclear cells (PBMNCs). In tubule formation assays with human umbilical vein endothelial cells, ECFCs stimulated 1.5-fold more capillary growth than PBMNCs, and this effect was suppressed by antibodies against VEGF and FGF-2. Using an immunodeficient hindlimb ischemia model and laser-Doppler imaging, we evaluated the limb salvage rate and blood perfusion after intramuscular implantation of ECFCs. ECFC implantation increased both the salvage rate (38{\%} vs. 0{\%}, P < 0.05) and the blood perfusion (82.8{\%} vs. 65.6{\%}, P < 0.01). In addition, ECFCs implantation also significantly increased capillaries with recruitment of vascular smooth muscle cells and the capillary density was 1.6-fold higher than in the control group. Continuous production of human VEGF from ECFCs in the skeletal muscle was confirmed at least 7 days after the implantation. Implantation of ECFCs promoted angiogenesis in ischemic limbs by supplying angiogenic cytokines (VEGF and FGF-2), suggesting a possible novel strategy for therapeutic angiogenesis.",
author = "Shuji Sasaki and Toyoshi Inoguchi and Koichiro Muta and Yasunobu Abe and Min Zhang and Hiasa Ken-Ichi and Kensuke Egashira and Noriyuki Sonoda and Kunihisa Kobayashi and Ryoichi Takayanagi and Hajime Nawata",
year = "2007",
month = "1",
day = "1",
doi = "10.1152/ajpheart.00343.2006",
language = "English",
volume = "292",
journal = "American Journal of Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "1",

}

TY - JOUR

T1 - Therapeutic angiogenesis by ex vivo expanded erythroid progenitor cells

AU - Sasaki, Shuji

AU - Inoguchi, Toyoshi

AU - Muta, Koichiro

AU - Abe, Yasunobu

AU - Zhang, Min

AU - Ken-Ichi, Hiasa

AU - Egashira, Kensuke

AU - Sonoda, Noriyuki

AU - Kobayashi, Kunihisa

AU - Takayanagi, Ryoichi

AU - Nawata, Hajime

PY - 2007/1/1

Y1 - 2007/1/1

N2 - Recent reports have demonstrated that erythroid progenitor cells contain and secrete various angiogenic cytokines. Here, the impact of erythroid colony-forming cell (ECFC) implantation on therapeutic angiogenesis was investigated in murine models of hindlimb ischemia. During the in vitro differentiation, vascular endothelial growth factor (VEGF) secretion by ECFCs was observed from day 3 (burst-forming unit erythroid cells) to day 10 (erythroblasts). ECFCs from day 5 to day 7 (colony-forming unit erythroid cells) showed the highest VEGF productivity, and day 6 ECFCs were used for the experiments. ECFCs contained larger amounts of VEGF and fibroblast growth factor-2 (FGF-2) than peripheral blood mononuclear cells (PBMNCs). In tubule formation assays with human umbilical vein endothelial cells, ECFCs stimulated 1.5-fold more capillary growth than PBMNCs, and this effect was suppressed by antibodies against VEGF and FGF-2. Using an immunodeficient hindlimb ischemia model and laser-Doppler imaging, we evaluated the limb salvage rate and blood perfusion after intramuscular implantation of ECFCs. ECFC implantation increased both the salvage rate (38% vs. 0%, P < 0.05) and the blood perfusion (82.8% vs. 65.6%, P < 0.01). In addition, ECFCs implantation also significantly increased capillaries with recruitment of vascular smooth muscle cells and the capillary density was 1.6-fold higher than in the control group. Continuous production of human VEGF from ECFCs in the skeletal muscle was confirmed at least 7 days after the implantation. Implantation of ECFCs promoted angiogenesis in ischemic limbs by supplying angiogenic cytokines (VEGF and FGF-2), suggesting a possible novel strategy for therapeutic angiogenesis.

AB - Recent reports have demonstrated that erythroid progenitor cells contain and secrete various angiogenic cytokines. Here, the impact of erythroid colony-forming cell (ECFC) implantation on therapeutic angiogenesis was investigated in murine models of hindlimb ischemia. During the in vitro differentiation, vascular endothelial growth factor (VEGF) secretion by ECFCs was observed from day 3 (burst-forming unit erythroid cells) to day 10 (erythroblasts). ECFCs from day 5 to day 7 (colony-forming unit erythroid cells) showed the highest VEGF productivity, and day 6 ECFCs were used for the experiments. ECFCs contained larger amounts of VEGF and fibroblast growth factor-2 (FGF-2) than peripheral blood mononuclear cells (PBMNCs). In tubule formation assays with human umbilical vein endothelial cells, ECFCs stimulated 1.5-fold more capillary growth than PBMNCs, and this effect was suppressed by antibodies against VEGF and FGF-2. Using an immunodeficient hindlimb ischemia model and laser-Doppler imaging, we evaluated the limb salvage rate and blood perfusion after intramuscular implantation of ECFCs. ECFC implantation increased both the salvage rate (38% vs. 0%, P < 0.05) and the blood perfusion (82.8% vs. 65.6%, P < 0.01). In addition, ECFCs implantation also significantly increased capillaries with recruitment of vascular smooth muscle cells and the capillary density was 1.6-fold higher than in the control group. Continuous production of human VEGF from ECFCs in the skeletal muscle was confirmed at least 7 days after the implantation. Implantation of ECFCs promoted angiogenesis in ischemic limbs by supplying angiogenic cytokines (VEGF and FGF-2), suggesting a possible novel strategy for therapeutic angiogenesis.

UR - http://www.scopus.com/inward/record.url?scp=33846190243&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33846190243&partnerID=8YFLogxK

U2 - 10.1152/ajpheart.00343.2006

DO - 10.1152/ajpheart.00343.2006

M3 - Article

VL - 292

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0363-6135

IS - 1

ER -