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Title: Efficient long-term survival of cell grafts after myocardial infarction with thick viable cardiac tissue entirely from pluripotent stem cells
Authors: Matsuo, Takehiko
Masumoto, Hidetoshi  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0002-4059-2827 (unconfirmed)
Tajima, Shuhei
Ikuno, Takeshi
Katayama, Shiori
Minakata, Kenji
Ikeda, Tadashi  kyouindb  KAKEN_id
Yamamizu, Kohei
Tabata, Yasuhiko  kyouindb  KAKEN_id
Sakata, Ryuzo
Yamashita, Jun K.
Author's alias: 松尾, 武彦
南方, 謙二
池田, 義
山水, 康平
田畑, 泰彦
坂田, 隆造
山下, 潤
Issue Date: 20-Nov-2015
Publisher: Nature Publishing Group
Journal title: Scientific Reports
Volume: 5
Thesis number: 16842
Abstract: Poor engraftment of cells after transplantation to the heart is a common and unresolved problem in the cardiac cell therapies. We previously generated cardiovascular cell sheets entirely from pluripotent stem cells with cardiomyocytes, endothelial cells and vascular mural cells. Though sheet transplantation showed a better engraftment and improved cardiac function after myocardial infarction, stacking limitation (up to 3 sheets) by hypoxia hampered larger structure formation and long-term survival of the grafts. Here we report an efficient method to overcome the stacking limitation. Insertion of gelatin hydrogel microspheres (GHMs) between each cardiovascular cell sheet broke the viable limitation via appropriate spacing and fluid impregnation with GHMs. Fifteen sheets with GHMs (15-GHM construct; >1mm thickness) were stacked within several hours and viable after 1 week in vitro. Transplantation of 5-GHM constructs (≈2×106 of total cells) to a rat myocardial infarction model showed rapid and sustained functional improvements. The grafts were efficiently engrafted as multiple layered cardiovascular cells accompanied by functional capillary networks. Large engrafted cardiac tissues (0.8mm thickness with 40 cell layers) successfully survived 3 months after TX. We developed an efficient method to generate thicker viable tissue structures and achieve long-term survival of the cell graft to the heart.
Description: 心臓組織シートを、細胞が生きた状態で簡便に積層化する方法の開発. 京都大学プレスリリース. 2015-11-27.
Rights: © 2015, Nature Publishing Group. All rights reserved.
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/2433/210505
DOI(Published Version): 10.1038/srep16842
Related Link: https://www.kyoto-u.ac.jp/ja/research-news/2015-11-27
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