Designer artificial membrane binding proteins direct stem cells to the myocardium

Wenjin Xiao; Tom I P Green; Xiaowen Liang; Rosalia Cuahtecontzi Delint; Guillaume Perry; Michael S Roberts; Kris Le Vay; Catherine Back; Raimondo Ascione; Haolu Wang; Paul Race; Adam Perriman

doi:10.1039/C9SC02650A

Designer artificial membrane binding proteins direct stem cells to the myocardium

Wenjin Xiao, Tom I P Green, Xiaowen Liang, Rosalia Cuahtecontzi Delint, Guillaume Perry, Michael S Roberts, Kris Le Vay, Catherine Back, Raimondo Ascione, Haolu Wang, Paul Race, Adam Perriman

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Abstract

We present a new cell membrane modification methodology where the inherent heart tissue homing properties of the infectious bacteria Streptococcus gordonii are transferred to human stem cells. This is achieved via the rational design of a
chimeric protein-polymer surfactant cell membrane binding construct, comprising the cardiac fibronectin (Fn) binding domain of the bacterial adhesin protein CshA fused to a supercharged protein. Significantly, the protein-polymer
surfactant hybrid spontaneously inserts into the plasma membrane of stem cells without cytotoxicity, instilling the cells with a high affinity for immobilized fibronectin. Moreover, we show that this cell membrane reengineering approach
significantly improves retention and homing of stem cells delivered either intracardially or intravenously to the myocardium in a mouse model.

Original language	English
Pages (from-to)	7610 - 7618
Number of pages	9
Journal	Chemical Science
Volume	10
Issue number	32
DOIs	https://doi.org/10.1039/C9SC02650A
Publication status	Published - 3 Jul 2019

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BrisSynBio
Bristol BioDesign Institute

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Synthetic biology

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BrisSynBio: Bristol Centre for Synthetic Biology
Woolfson, D. N.
31/07/14 → 31/03/22
Project: Research

Chemical Science Xiao et al
Perriman, A. W. (Contributor), Carter, B. (Creator), Zampetakis, I. (Creator), Zhang, W. (Creator), Delint, R. C. (Creator), Klemperer, R. (Creator), Day, G. J. (Creator), Richardson, T. (Creator), Hickton, B. (Creator) & Coe, D. (Creator), University of Bristol, 3 Jul 2019
DOI: 10.5523/bris.21w0xiagciryg2b1gcdaxn5z2q, http://data.bris.ac.uk/data/dataset/21w0xiagciryg2b1gcdaxn5z2q
Dataset

Professor Raimondo Ascione
- R.Ascionebristol.acuk
- Elizabeth Blackwell Institute for Health Research
- Bristol Medical School (THS) - Professor of Cardiac Surgery and Translational Research and Director of TBRC
Person: Academic , Member

Cite this

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title = "Designer artificial membrane binding proteins direct stem cells to the myocardium",

abstract = "We present a new cell membrane modification methodology where the inherent heart tissue homing properties of the infectious bacteria Streptococcus gordonii are transferred to human stem cells. This is achieved via the rational design of achimeric protein-polymer surfactant cell membrane binding construct, comprising the cardiac fibronectin (Fn) binding domain of the bacterial adhesin protein CshA fused to a supercharged protein. Significantly, the protein-polymersurfactant hybrid spontaneously inserts into the plasma membrane of stem cells without cytotoxicity, instilling the cells with a high affinity for immobilized fibronectin. Moreover, we show that this cell membrane reengineering approachsignificantly improves retention and homing of stem cells delivered either intracardially or intravenously to the myocardium in a mouse model.",

keywords = "Synthetic biology",

author = "Wenjin Xiao and Green, {Tom I P} and Xiaowen Liang and {Cuahtecontzi Delint}, Rosalia and Guillaume Perry and Roberts, {Michael S} and {Le Vay}, Kris and Catherine Back and Raimondo Ascione and Haolu Wang and Paul Race and Adam Perriman",

year = "2019",

month = jul,

day = "3",

doi = "10.1039/C9SC02650A",

language = "English",

volume = "10",

pages = "7610 -- 7618",

journal = "Chemical Science",

issn = "2041-6520",

publisher = "Royal Society of Chemistry",

number = "32",

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TY - JOUR

T1 - Designer artificial membrane binding proteins direct stem cells to the myocardium

AU - Xiao, Wenjin

AU - Green, Tom I P

AU - Liang, Xiaowen

AU - Cuahtecontzi Delint, Rosalia

AU - Perry, Guillaume

AU - Roberts, Michael S

AU - Le Vay, Kris

AU - Back, Catherine

AU - Ascione, Raimondo

AU - Wang, Haolu

AU - Race, Paul

AU - Perriman, Adam

PY - 2019/7/3

Y1 - 2019/7/3

N2 - We present a new cell membrane modification methodology where the inherent heart tissue homing properties of the infectious bacteria Streptococcus gordonii are transferred to human stem cells. This is achieved via the rational design of achimeric protein-polymer surfactant cell membrane binding construct, comprising the cardiac fibronectin (Fn) binding domain of the bacterial adhesin protein CshA fused to a supercharged protein. Significantly, the protein-polymersurfactant hybrid spontaneously inserts into the plasma membrane of stem cells without cytotoxicity, instilling the cells with a high affinity for immobilized fibronectin. Moreover, we show that this cell membrane reengineering approachsignificantly improves retention and homing of stem cells delivered either intracardially or intravenously to the myocardium in a mouse model.

AB - We present a new cell membrane modification methodology where the inherent heart tissue homing properties of the infectious bacteria Streptococcus gordonii are transferred to human stem cells. This is achieved via the rational design of achimeric protein-polymer surfactant cell membrane binding construct, comprising the cardiac fibronectin (Fn) binding domain of the bacterial adhesin protein CshA fused to a supercharged protein. Significantly, the protein-polymersurfactant hybrid spontaneously inserts into the plasma membrane of stem cells without cytotoxicity, instilling the cells with a high affinity for immobilized fibronectin. Moreover, we show that this cell membrane reengineering approachsignificantly improves retention and homing of stem cells delivered either intracardially or intravenously to the myocardium in a mouse model.

KW - Synthetic biology

U2 - 10.1039/C9SC02650A

DO - 10.1039/C9SC02650A

M3 - Article (Academic Journal)

VL - 10

SP - 7610

EP - 7618

JO - Chemical Science

JF - Chemical Science

SN - 2041-6520

IS - 32

ER -

Designer artificial membrane binding proteins direct stem cells to the myocardium

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BrisSynBio: Bristol Centre for Synthetic Biology

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Chemical Science Xiao et al

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Professor Raimondo Ascione

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