title: Synthetic molecules that protect cells from anoikis and their use in cell transplantation.
abstract: 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.
authors.affiliation: Institute for Integrated Cell-Material Sciences (WPI-iCeMS) and Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011 (Japan); Graduate School of Medicine Kyoto University (Japan).
authors.forename: Heidie L
authors.initials: HL
authors.lastname: Frisco-Cabanos
authors.forename: Mizuki
authors.initials: M
authors.lastname: Watanabe
authors.forename: Naoki
authors.initials: N
authors.lastname: Okumura
authors.forename: Kosuke
authors.initials: K
authors.lastname: Kusamori
authors.forename: Naohiro
authors.initials: N
authors.lastname: Takemoto
authors.forename: Junichiro
authors.initials: J
authors.lastname: Takaya
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Sato
authors.forename: Sayumi
authors.initials: S
authors.lastname: Yamazoe
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Takakura
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kinoshita
authors.forename: Makiya
authors.initials: M
authors.lastname: Nishikawa
authors.forename: Noriko
authors.initials: N
authors.lastname: Koizumi
authors.forename: Motonari
authors.initials: M
authors.lastname: Uesugi
mesh_terms: D000818:Animals; D023102:Anoikis / Q000187:drug effects*; D002448:Cell Adhesion / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D017690:Cell Transplantation / Q000379:methods; D002478:Cells, Cultured; D019012:Integrin beta1 / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D020011:Protective Agents / Q000737:chemistry* / Q000494:pharmacology*; D011817:Rabbits; D053671:Syndecan-4 / Q000378:metabolism
chemical_list: D019012:Integrin beta1; D010455:Peptides; D020011:Protective Agents; D053671:Syndecan-4
keywords: adhesamine; anoikis; cell engraftment; peptides; self-assembly