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Journal of Translational Medicine

, 6:54

First Online: 30 September 2008Received: 22 May 2008Accepted: 30 September 2008DOI: 10.1186-1479-5876-6-54

Cite this article as: Oyamada, N., Itoh, H., Sone, M. et al. J Transl Med 2008 6: 54. doi:10.1186-1479-5876-6-54

Abstract

BackgroundWe 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.

MethodsPhosphate 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.

ResultsTransplanted 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.

ConclusionTransplantation 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.

AbbreviationsES cellsEmbryonic stem cells

VEGF-R2vascular endothelial growth factor receptor type 2

ECsendothelial cells

MCsmural cells

hMNCshuman peripheral blood mononuclear cells

MCAomiddle cerebral artery occlusion

αSMAalpha smooth muscle actin

hES-ECs+MCsa mixture of ECs and MCs derived from human ES cells

hES-ECsECs derived from human ES cells

hES-MCsMCs derived from human ES cells.

Electronic supplementary materialThe online version of this article doi:10.1186-1479-5876-6-54 contains supplementary material, which is available to authorized users.

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Autor: Naofumi Oyamada - Hiroshi Itoh - Masakatsu Sone - Kenichi Yamahara - Kazutoshi Miyashita - Kwijun Park - Daisuke Taura - Me

Fuente: https://link.springer.com/







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