TY - JOUR
T1 - Multifunctionalization of Cells with a Self-Assembling Molecule to Enhance Cell Engraftment
AU - Takashima, Ippei
AU - Kusamori, Kosuke
AU - Hakariya, Hayase
AU - Takashima, Megumi
AU - Vu, Thi Hue
AU - Mizukami, Yuya
AU - Noda, Naotaka
AU - Takayama, Yukiya
AU - Katsuda, Yousuke
AU - Sato, Shin Ichi
AU - Takakura, Yoshinobu
AU - Nishikawa, Makiya
AU - Uesugi, Motonari
N1 - Funding Information:
The authors thank Nagase & Co., Ltd. for sharing chemical samples, R. Asano and Y. Takemoto for the technical support of biological experiments, T. Morii and E. Nakata for ITC and MALDI-TOF-MS measurements, T. Ogawa and H. Kurata for cryo-TEM observation, F. Quiocho for editing the manuscript, and Y. Tsujii for DLS technical support. This work was supported by JSPS (Grants 16K16641 to I.T. and 26220206 to M.U.), the Collaborative Research Program of the Institute for Chemical Research, Kyoto University. This work was inspired by the international and interdisciplinary environments of WPI-iCeMS and JSPS CORE-to-CORE Program, “Asian Chemical Biology Initiative.” The upgrade of the confocal microscope was supported by the New Energy and Industrial Technology Development Organization (NEDO) of Japan and Yokogawa Electric Corporation. This study used an FE-SEM ULTRA 55 (Carl Zeiss NTS GmbH) in the Application of DuET and MUSTER for Industrial Research Engineering (ADMIRE) at the Institute of Advanced Energy, Kyoto University, and a 600-MHz NMR spectrometer in the Joint Usage/Research Center (JURC) at the Institute for Chemical Research, Kyoto University.
Publisher Copyright:
© 2019 American Chemical Society.
PY - 2019/4/19
Y1 - 2019/4/19
N2 - Cell-based therapy is a promising approach to restoring lost functions to compromised organs. However, the issue of inefficient cell engraftment remains to be resolved. Herein, we take a chemical approach to facilitate cell engraftment by using self-assembling molecules which modify two cellular traits: cell survival and invasiveness. In this system, the self-assembling molecule induces syndecan-4 clusters on the cellular surface, leading to enhanced cell viability. Further integration with Halo-tag technology provided this self-assembly structure with matrix metalloproteinase-2 to functionalize cells with cell-invasion activity. In vivo experiments showed that the pretreated cells were able to survive injection and then penetrate and engraft into the host tissue, demonstrating that the system enhances cell engraftment. Therefore, cell-surface modification via an alliance between self-assembling molecules and ligation technologies may prove to be a promising method for cell engraftment.
AB - Cell-based therapy is a promising approach to restoring lost functions to compromised organs. However, the issue of inefficient cell engraftment remains to be resolved. Herein, we take a chemical approach to facilitate cell engraftment by using self-assembling molecules which modify two cellular traits: cell survival and invasiveness. In this system, the self-assembling molecule induces syndecan-4 clusters on the cellular surface, leading to enhanced cell viability. Further integration with Halo-tag technology provided this self-assembly structure with matrix metalloproteinase-2 to functionalize cells with cell-invasion activity. In vivo experiments showed that the pretreated cells were able to survive injection and then penetrate and engraft into the host tissue, demonstrating that the system enhances cell engraftment. Therefore, cell-surface modification via an alliance between self-assembling molecules and ligation technologies may prove to be a promising method for cell engraftment.
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U2 - 10.1021/acschembio.9b00109
DO - 10.1021/acschembio.9b00109
M3 - Article
C2 - 30807095
AN - SCOPUS:85064408774
SN - 1554-8929
VL - 14
SP - 775
EP - 783
JO - ACS Chemical Biology
JF - ACS Chemical Biology
IS - 4
ER -