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

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 - J Transl Med (2008)

Bottom Line: 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.Transplanted ECs were successfully incorporated into host capillaries and MCs were distributed in the areas surrounding endothelial tubes.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan. kanu@kuhp.kyoto-u.ac.jp

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.

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RT-PCR analysis of mRNA expression of VEGF, bFGF, HGF, and PDGF-B in hAoSMCs and hES-MCs. bp indicates base pair.
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Figure 7: RT-PCR analysis of mRNA expression of VEGF, bFGF, HGF, and PDGF-B in hAoSMCs and hES-MCs. bp indicates base pair.

Mentions: We investigated whether the transplanted hES-MCs produced major angiogenic factors such as VEGF, bFGF, HGF and PDGF-BB. Reverse transcription-polymerase chain reaction (RT-PCR) analysis detected mRNA expression of VEGF165, VEGF189, bFGF and HGF in MCs as well as hAoSMCs (Figure 7). In addition, we measured the protein concentration of these angiogenic factors in culture media of hES-MCs by enzyme-linked immunosorbent assay (ELISA). However, the concentration of all factors did not reach the detectable level as follows; the concentration of VEGF, bFGF or HGF was lower than 20 pg/ml, 10 pg/ml, or 0.3 ng/ml.


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

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 - J Transl Med (2008)

RT-PCR analysis of mRNA expression of VEGF, bFGF, HGF, and PDGF-B in hAoSMCs and hES-MCs. bp indicates base pair.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2567291&req=5

Figure 7: RT-PCR analysis of mRNA expression of VEGF, bFGF, HGF, and PDGF-B in hAoSMCs and hES-MCs. bp indicates base pair.
Mentions: We investigated whether the transplanted hES-MCs produced major angiogenic factors such as VEGF, bFGF, HGF and PDGF-BB. Reverse transcription-polymerase chain reaction (RT-PCR) analysis detected mRNA expression of VEGF165, VEGF189, bFGF and HGF in MCs as well as hAoSMCs (Figure 7). In addition, we measured the protein concentration of these angiogenic factors in culture media of hES-MCs by enzyme-linked immunosorbent assay (ELISA). However, the concentration of all factors did not reach the detectable level as follows; the concentration of VEGF, bFGF or HGF was lower than 20 pg/ml, 10 pg/ml, or 0.3 ng/ml.

Bottom Line: 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.Transplanted ECs were successfully incorporated into host capillaries and MCs were distributed in the areas surrounding endothelial tubes.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan. kanu@kuhp.kyoto-u.ac.jp

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.

Show MeSH
Related in: MedlinePlus