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Synthetic Molecules that Protect Cells from Anoikis and Their Use in Cell Transplantation
Author(s) -
FriscoCabanos Heidie L.,
Watanabe Mizuki,
Okumura Naoki,
Kusamori Kosuke,
Takemoto Naohiro,
Takaya Junichiro,
Sato Shinichi,
Yamazoe Sayumi,
Takakura Yoshinobu,
Kinoshita Shigeru,
Nishikawa Makiya,
Koizumi Noriko,
Uesugi Motonari
Publication year - 2014
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201405829
Subject(s) - anoikis , microbiology and biotechnology , transplantation , integrin , chemistry , cell , extracellular matrix , cell adhesion molecule , heparan sulfate , programmed cell death , apoptosis , biology , biochemistry , medicine , surgery
One of the major problems encountered in cell transplantation is the low level of survival of transplanted cells due to detachment‐induced apoptosis, called anoikis. The present study reports on the chemical synthesis and biological evaluation of water‐soluble molecules that protect suspended cells from anoikis. The synthetic molecules bind to and induce clusters of integrins and heparan‐sulfate‐bound syndecans, two classes of receptors that are important for extracellular matrix‐mediated cell survival. Molecular biological analysis indicates that such molecules prolong the survival of suspended NIH3T3 cells, at least in part, by promoting clustering of syndecan‐4 and integrin β1 on the cell surface, leading to the activation of small GTPase Rac‐1 and Akt. In vivo experiments using animal disease models demonstrated the ability of the molecules to improve cell engraftment. The cluster‐inducing molecules may provide a starting point for the design of new synthetic tools for cell‐based therapy.