biostudies-literatureZhao WNIDCR NIH HHSNCRR NIH HHSNHLBI NIH HHS3045-56https://www.ebi.ac.uk/biostudies/studies/S-EPMC3157693biostudies-literatureUnknown25(9)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.FASEB journal : official publication of the Federation of American Societies for Experimental BiologyMimicking the inflammatory cell adhesion cascade by nucleic acid aptamer programmed cell-cell interactions.PMC3157693HL-097172DE-019191HL-095722R21 HL097172R03 DE019191P40RR017447P40 RR017447R01 HL095722Schafer SSarkar DZhao WDroujinine IATeo WKumar NKarnik RCui CHZhang LKarp JMLoh WfalseMimicking the inflammatory cell adhesion cascade by nucleic acid aptamer programmed cell-cell interactions.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.2011-01-01T00:00:00Z2011 Sep2021-03-06T08:47:41Z2019-03-27T00:01:31ZS-EPMC31576932165319210.1096/fj.10-178384