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

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 con...

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Bibliographic Details
Published in:Chemical science (Cambridge) 2019-08, Vol.1 (32), p.761-7618
Main Authors: Xiao, Wenjin, Green, Thomas I. P, Liang, Xiaowen, Delint, Rosalia Cuahtecontzi, Perry, Guillaume, Roberts, Michael S, Le Vay, Kristian, Back, Catherine R, Ascione, Raimomdo, Wang, Haolu, Race, Paul R, Perriman, Adam W
Format: Article
Language:English
Subjects:
Binding
Biochemistry
Biochemistry, Molecular Biology
Bioengineering
Biomaterials
Cell membranes
Fibronectin
Heart
Homing
Inserts
Life Sciences
Myocardium
Polymers
Proteins
Reengineering
Stem cells
Surfactants
Toxicity
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Summary: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. 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.
ISSN:2041-6520
2041-6539
DOI:10.1039/c9sc02650a