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Title: Enhanced engraftment, proliferation, and therapeutic potential in heart using optimized human iPSC-derived cardiomyocytes
Authors: Funakoshi, Shunsuke
Miki, Kenji  kyouindb  KAKEN_id
Takaki, Tadashi
Okubo, Chikako
Hatani, Takeshi
Chonabayashi, Kazuhisa  kyouindb  KAKEN_id
Nishikawa, Misato
Takei, Ikue
Oishi, Akiko
Narita, Megumi
Hoshijima, Masahiko
Kimura, Takeshi  kyouindb  KAKEN_id
Yamanaka, Shinya  kyouindb  KAKEN_id
Yoshida, Yoshinori
Author's alias: 舟越, 俊介
蝶名林, 和久
成田, 恵
山中, 伸弥
吉田, 善紀
Issue Date: 8-Jan-2016
Publisher: Nature Publishing Group
Journal title: Scientific Reports
Volume: 6
Thesis number: 19111
Abstract: Human pluripotent stem cell-derived cardiomyocytes (CMs) are a promising tool for cardiac cell therapy. Although transplantation of induced pluripotent stem cell (iPSC)-derived CMs have been reported in several animal models, the treatment effect was limited, probably due to poor optimization of the injected cells. To optimize graft cells for cardiac reconstruction, we compared the engraftment efficiency of intramyocardially-injected undifferentiated-iPSCs, day4 mesodermal cells, and day8, day20, and day30 purified iPSC-CMs after initial differentiation by tracing the engraftment ratio (ER) using in vivo bioluminescence imaging. This analysis revealed the ER of day20 CMs was significantly higher compared to other cells. Transplantation of day20 CMs into the infarcted hearts of immunodeficient mice showed good engraftment, and echocardiography showed significant functional improvement by cell therapy. Moreover, the imaging signal and ratio of Ki67-positive CMs at 3 months post injection indicated engrafted CMs proliferated in the host heart. Although this graft growth reached a plateau at 3 months, histological analysis confirmed progressive maturation from 3 to 6 months. These results suggested that day20 CMs had very high engraftment, proliferation, and therapeutic potential in host mouse hearts. They also demonstrate this model can be used to track the fate of transplanted cells over a long time.
Description: 最も移植効果の高い心筋細胞のステージを発見 : ヒトiPS細胞から分化させた心筋細胞の移植効果を高める. 京都大学プレスリリース. 2016-01-08.
Rights: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
URI: http://hdl.handle.net/2433/212055
DOI(Published Version): 10.1038/srep19111
PubMed ID: 26743035
Related Link: http://www.kyoto-u.ac.jp/ja/research/research_results/2015/160108_1.html/
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