Transplantation of vascular cells derived from human embryonic stem cells contributes to vascular regeneration after stroke in mice

Naofumi Oyamada, Hiroshi Itoh, Masakatsu Sone, Kenichi Yamahara, Kazutoshi Miyashita, Kwijun Park, Daisuke Taura, Megumi Inuzuka, Takuhiro Sonoyama, Hirokazu Tsujimoto, Yasutomo Fukunaga, Naohisa Tamura, Kazuwa Nakao

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Background: We previously demonstrated that vascular endothelial growth factor receptor type 2 (VEGF-R2)-positive cells induced from mouse embryonic stem (ES) cells can differentiate into both endothelial cells (ECs) and mural cells (MCs) and these vascular cells construct blood vessel structures in vitro. Recently, we have also established a method for the large-scale expansion of ECs and MCs derived from human ES cells. We examined the potential of vascular cells derived from human ES cells to contribute to vascular regeneration and to provide therapeutic benefit for the ischemic brain. Methods: Phosphate buffered saline, human peripheral blood mononuclear cells (hMNCs), ECs-, MCs-, or the mixture of ECs and MCs derived from human ES cells were intra-arterially transplanted into mice after transient middle cerebral artery occlusion (MCAo). Results: Transplanted ECs were successfully incorporated into host capillaries and MCs were distributed in the areas surrounding endothelial tubes. The cerebral blood flow and the vascular density in the ischemic striatum on day 28 after MCAo had significantly improved in ECs-, MCs- and ECs+MCs-transplanted mice compared to that of mice injected with saline or transplanted with hMNCs. Moreover, compared to saline-injected or hMNC-transplanted mice, significant reduction of the infarct volume and of apoptosis as well as acceleration of neurological recovery were observed on day 28 after MCAo in the cell mixture-transplanted mice. Conclusion: Transplantation of ECs and MCs derived from undifferentiated human ES cells have a potential to contribute to therapeutic vascular regeneration and consequently reduction of infarct area after stroke.

Original languageEnglish
Article number54
JournalJournal of Translational Medicine
Volume6
DOIs
Publication statusPublished - 2008 Sep 30

Fingerprint

Cell Transplantation
Endothelial cells
Stem cells
Blood Vessels
Regeneration
Stroke
Endothelial Cells
Blood
Middle Cerebral Artery Infarction
Blood Cells
Vascular Endothelial Growth Factor Receptor-2
Human Embryonic Stem Cells
Cerebrovascular Circulation
Blood vessels
Brain
Phosphates
Cells
Apoptosis
Recovery
Transplantation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Transplantation of vascular cells derived from human embryonic stem cells contributes to vascular regeneration after stroke in mice. / Oyamada, Naofumi; Itoh, Hiroshi; Sone, Masakatsu; Yamahara, Kenichi; Miyashita, Kazutoshi; Park, Kwijun; Taura, Daisuke; Inuzuka, Megumi; Sonoyama, Takuhiro; Tsujimoto, Hirokazu; Fukunaga, Yasutomo; Tamura, Naohisa; Nakao, Kazuwa.

In: Journal of Translational Medicine, Vol. 6, 54, 30.09.2008.

Research output: Contribution to journalArticle

Oyamada, N, Itoh, H, Sone, M, Yamahara, K, Miyashita, K, Park, K, Taura, D, Inuzuka, M, Sonoyama, T, Tsujimoto, H, Fukunaga, Y, Tamura, N & Nakao, K 2008, 'Transplantation of vascular cells derived from human embryonic stem cells contributes to vascular regeneration after stroke in mice', Journal of Translational Medicine, vol. 6, 54. https://doi.org/10.1186/1479-5876-6-54
Oyamada, Naofumi ; Itoh, Hiroshi ; Sone, Masakatsu ; Yamahara, Kenichi ; Miyashita, Kazutoshi ; Park, Kwijun ; Taura, Daisuke ; Inuzuka, Megumi ; Sonoyama, Takuhiro ; Tsujimoto, Hirokazu ; Fukunaga, Yasutomo ; Tamura, Naohisa ; Nakao, Kazuwa. / Transplantation of vascular cells derived from human embryonic stem cells contributes to vascular regeneration after stroke in mice. In: Journal of Translational Medicine. 2008 ; Vol. 6.
@article{ff9d7a34c2f94836ba693dbe4e0f9735,
title = "Transplantation of vascular cells derived from human embryonic stem cells contributes to vascular regeneration after stroke in mice",
abstract = "Background: We previously demonstrated that vascular endothelial growth factor receptor type 2 (VEGF-R2)-positive cells induced from mouse embryonic stem (ES) cells can differentiate into both endothelial cells (ECs) and mural cells (MCs) and these vascular cells construct blood vessel structures in vitro. Recently, we have also established a method for the large-scale expansion of ECs and MCs derived from human ES cells. We examined the potential of vascular cells derived from human ES cells to contribute to vascular regeneration and to provide therapeutic benefit for the ischemic brain. Methods: Phosphate buffered saline, human peripheral blood mononuclear cells (hMNCs), ECs-, MCs-, or the mixture of ECs and MCs derived from human ES cells were intra-arterially transplanted into mice after transient middle cerebral artery occlusion (MCAo). Results: Transplanted ECs were successfully incorporated into host capillaries and MCs were distributed in the areas surrounding endothelial tubes. The cerebral blood flow and the vascular density in the ischemic striatum on day 28 after MCAo had significantly improved in ECs-, MCs- and ECs+MCs-transplanted mice compared to that of mice injected with saline or transplanted with hMNCs. Moreover, compared to saline-injected or hMNC-transplanted mice, significant reduction of the infarct volume and of apoptosis as well as acceleration of neurological recovery were observed on day 28 after MCAo in the cell mixture-transplanted mice. Conclusion: Transplantation of ECs and MCs derived from undifferentiated human ES cells have a potential to contribute to therapeutic vascular regeneration and consequently reduction of infarct area after stroke.",
author = "Naofumi Oyamada and Hiroshi Itoh and Masakatsu Sone and Kenichi Yamahara and Kazutoshi Miyashita and Kwijun Park and Daisuke Taura and Megumi Inuzuka and Takuhiro Sonoyama and Hirokazu Tsujimoto and Yasutomo Fukunaga and Naohisa Tamura and Kazuwa Nakao",
year = "2008",
month = "9",
day = "30",
doi = "10.1186/1479-5876-6-54",
language = "English",
volume = "6",
journal = "Journal of Translational Medicine",
issn = "1479-5876",
publisher = "BioMed Central",

}

TY - JOUR

T1 - Transplantation of vascular cells derived from human embryonic stem cells contributes to vascular regeneration after stroke in mice

AU - Oyamada, Naofumi

AU - Itoh, Hiroshi

AU - Sone, Masakatsu

AU - Yamahara, Kenichi

AU - Miyashita, Kazutoshi

AU - Park, Kwijun

AU - Taura, Daisuke

AU - Inuzuka, Megumi

AU - Sonoyama, Takuhiro

AU - Tsujimoto, Hirokazu

AU - Fukunaga, Yasutomo

AU - Tamura, Naohisa

AU - Nakao, Kazuwa

PY - 2008/9/30

Y1 - 2008/9/30

N2 - Background: We previously demonstrated that vascular endothelial growth factor receptor type 2 (VEGF-R2)-positive cells induced from mouse embryonic stem (ES) cells can differentiate into both endothelial cells (ECs) and mural cells (MCs) and these vascular cells construct blood vessel structures in vitro. Recently, we have also established a method for the large-scale expansion of ECs and MCs derived from human ES cells. We examined the potential of vascular cells derived from human ES cells to contribute to vascular regeneration and to provide therapeutic benefit for the ischemic brain. Methods: Phosphate buffered saline, human peripheral blood mononuclear cells (hMNCs), ECs-, MCs-, or the mixture of ECs and MCs derived from human ES cells were intra-arterially transplanted into mice after transient middle cerebral artery occlusion (MCAo). Results: Transplanted ECs were successfully incorporated into host capillaries and MCs were distributed in the areas surrounding endothelial tubes. The cerebral blood flow and the vascular density in the ischemic striatum on day 28 after MCAo had significantly improved in ECs-, MCs- and ECs+MCs-transplanted mice compared to that of mice injected with saline or transplanted with hMNCs. Moreover, compared to saline-injected or hMNC-transplanted mice, significant reduction of the infarct volume and of apoptosis as well as acceleration of neurological recovery were observed on day 28 after MCAo in the cell mixture-transplanted mice. Conclusion: Transplantation of ECs and MCs derived from undifferentiated human ES cells have a potential to contribute to therapeutic vascular regeneration and consequently reduction of infarct area after stroke.

AB - Background: We previously demonstrated that vascular endothelial growth factor receptor type 2 (VEGF-R2)-positive cells induced from mouse embryonic stem (ES) cells can differentiate into both endothelial cells (ECs) and mural cells (MCs) and these vascular cells construct blood vessel structures in vitro. Recently, we have also established a method for the large-scale expansion of ECs and MCs derived from human ES cells. We examined the potential of vascular cells derived from human ES cells to contribute to vascular regeneration and to provide therapeutic benefit for the ischemic brain. Methods: Phosphate buffered saline, human peripheral blood mononuclear cells (hMNCs), ECs-, MCs-, or the mixture of ECs and MCs derived from human ES cells were intra-arterially transplanted into mice after transient middle cerebral artery occlusion (MCAo). Results: Transplanted ECs were successfully incorporated into host capillaries and MCs were distributed in the areas surrounding endothelial tubes. The cerebral blood flow and the vascular density in the ischemic striatum on day 28 after MCAo had significantly improved in ECs-, MCs- and ECs+MCs-transplanted mice compared to that of mice injected with saline or transplanted with hMNCs. Moreover, compared to saline-injected or hMNC-transplanted mice, significant reduction of the infarct volume and of apoptosis as well as acceleration of neurological recovery were observed on day 28 after MCAo in the cell mixture-transplanted mice. Conclusion: Transplantation of ECs and MCs derived from undifferentiated human ES cells have a potential to contribute to therapeutic vascular regeneration and consequently reduction of infarct area after stroke.

UR - http://www.scopus.com/inward/record.url?scp=54149111328&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=54149111328&partnerID=8YFLogxK

U2 - 10.1186/1479-5876-6-54

DO - 10.1186/1479-5876-6-54

M3 - Article

VL - 6

JO - Journal of Translational Medicine

JF - Journal of Translational Medicine

SN - 1479-5876

M1 - 54

ER -