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

研究成果: Article査読

41 被引用数 (Scopus)

抄録

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.

本文言語English
論文番号54
ジャーナルJournal of Translational Medicine
6
DOI
出版ステータスPublished - 2008 9 30

ASJC Scopus subject areas

  • 生化学、遺伝学、分子生物学(全般)

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