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


CONCLUSIONS
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.
Oyamada
Naofumi
N
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan. kanu@kuhp.kyoto-u.ac.jp
Itoh
Hiroshi
H
Sone
Masakatsu
M
Yamahara
Kenichi
K
Miyashita
Kazutoshi
K
Park
Kwijun
K
Taura
Daisuke
D
Inuzuka
Megumi
M
Sonoyama
Takuhiro
T
Tsujimoto
Hirokazu
H
Fukunaga
Yasutomo
Y
Tamura
Naohisa
N
Nakao
Kazuwa
K
D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D001773:Blood Cells / Q000166:cytology / Q000637:transplantation*; D001808:Blood Vessels / Q000473:pathology / Q000502:physiology*; D020520:Brain Infarction / Q000473:pathology / Q000503:physiopathology; D002460:Cell Line; D002560:Cerebrovascular Circulation; D019610:Cytoprotection; D053595:Embryonic Stem Cells / Q000166:cytology / Q000637:transplantation*; D005786:Gene Expression Regulation; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000139:chemically induced / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology; D020127:Recovery of Function; D012038:Regeneration; D020521:Stroke / Q000503:physiopathology* / Q000628:therapy*
D043925:Angiogenesis Inducing Agents