title: Mimicking the inflammatory cell adhesion cascade by nucleic acid aptamer programmed cell-cell interactions.
abstract: Nature has evolved effective cell adhesion mechanisms to deliver inflammatory cells to inflamed tissue; however, many culture-expanded therapeutic cells are incapable of targeting diseased tissues following systemic infusion, which represents a great challenge in cell therapy. Our aim was to develop simple approaches to program cell-cell interactions that would otherwise not exist toward cell targeting and understanding the complex biology of cell-cell interactions. We employed a chemistry approach to engineer P- or L-selectin binding nucleic acid aptamers onto mesenchymal stem cells (MSCs) to enable them to engage inflamed endothelial cells and leukocytes, respectively. We show for the first time that engineered cells with a single artificial adhesion ligand can recapitulate 3 critical cell interactions in the inflammatory cell adhesion cascade under dynamic flow conditions. Aptamer-engineered MSCs adhered on respective selectin surfaces under static conditions >10 times more efficiently than controls including scrambled-DNA modified MSCs. Significantly, engineered MSCs can be directly captured from the flow stream by selectin surfaces or selectin-expressing cells under flow conditions (≤2dyn/cm²). The simple chemistry approach and the versatility of aptamers permit the concept of engineered cell-cell interactions to be generically applicable for targeting cells to diseased tissues and elucidating the biology of cell-cell interactions.
authors.affiliation: Center for Regenerative Therapeutic, Department of Medicine, Brigham and Women's Hospital, Cambridge, Massachusetts, USA.
authors.forename: Weian
authors.initials: W
authors.lastname: Zhao
authors.forename: Weili
authors.initials: W
authors.lastname: Loh
authors.forename: Ilia A
authors.initials: IA
authors.lastname: Droujinine
authors.forename: Weisuong
authors.initials: W
authors.lastname: Teo
authors.forename: Namit
authors.initials: N
authors.lastname: Kumar
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schafer
authors.forename: Cheryl H
authors.initials: CH
authors.lastname: Cui
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.forename: Debanjan
authors.initials: D
authors.lastname: Sarkar
authors.forename: Rohit
authors.initials: R
authors.lastname: Karnik
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Karp
mesh_terms: D000818:Animals; D052157:Aptamers, Nucleotide / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology*; D002450:Cell Communication / Q000502:physiology*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000502:physiology*; D007249:Inflammation / Q000378:metabolism*; D019041:L-Selectin / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D019007:P-Selectin / Q000378:metabolism; D013499:Surface Properties
chemical_list: D052157:Aptamers, Nucleotide; D019007:P-Selectin; D019041:L-Selectin