Directing and Potentiating Stem Cell-Mediated Angiogenesis and Tissue Repair by Cell Surface E-Selectin Coating.
Stem cell therapy has emerged as a promising approach for treatment of a number of diseases, including delayed and non-healing wounds. However, targeted systemic delivery of therapeutic cells to the dysfunctional tissues remains one formidable challenge. Herein, we present a targeted nanocarrier-mediated cell delivery method by coating the surface of the cell to be delivered with dendrimer nanocarriers modified with adhesion molecules. Infused nanocarrier-coated cells reach to destination via recognition and association with the counterpart adhesion molecules highly or selectively expressed on the activated endothelium in diseased tissues. Once anchored on the activated endothelium, nanocarriers-coated transporting cells undergo transendothelial migration, extravasation and homing to the targeted tissues to execute their therapeutic role. We now demonstrate feasibility, efficacy and safety of our targeted nanocarrier for delivery of bone marrow cells (BMC) to cutaneous wound tissues and grafted corneas and its advantages over conventional BMC transplantation in mouse models for wound healing and neovascularization. This versatile platform is suited for targeted systemic delivery of virtually any type of therapeutic cell.
Department of Surgery, School of Medicine, University of Miami, Coral Gables, Florida, 33136, United States of America.
Zhao-Jun
ZJ
Liu
Department of Biochemistry and Molecular Biology, School of Medicine, University of Miami, Coral Gables, Florida, 33136, United States of America.|Dr. JT Macdonald Biomedical Nanotechnology Institute, University of Miami, Coral Gables, Florida, 33136, United States of America.
Pirouz
P
Daftarian
Department of Biochemistry and Molecular Biology, School of Medicine, University of Miami, Coral Gables, Florida, 33136, United States of America.
Letícia
L
Kovalski
Department of Surgery, School of Medicine, University of Miami, Coral Gables, Florida, 33136, United States of America.
Bo
B
Wang
Department of Surgery, School of Medicine, University of Miami, Coral Gables, Florida, 33136, United States of America.
Runxia
R
Tian
Department of Surgery, School of Medicine, University of Miami, Coral Gables, Florida, 33136, United States of America.
Diego M
DM
Castilla
Department of Biochemistry and Molecular Biology, School of Medicine, University of Miami, Coral Gables, Florida, 33136, United States of America.
Emre
E
Dikici
Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami, Coral Gables, Florida, 33136, United States of America.
Victor L
VL
Perez
Department of Biochemistry and Molecular Biology, School of Medicine, University of Miami, Coral Gables, Florida, 33136, United States of America.|Dr. JT Macdonald Biomedical Nanotechnology Institute, University of Miami, Coral Gables, Florida, 33136, United States of America.
Sapna
S
Deo
Department of Biochemistry and Molecular Biology, School of Medicine, University of Miami, Coral Gables, Florida, 33136, United States of America.|Dr. JT Macdonald Biomedical Nanotechnology Institute, University of Miami, Coral Gables, Florida, 33136, United States of America.
Sylvia
S
Daunert
Department of Surgery, School of Medicine, University of Miami, Coral Gables, Florida, 33136, United States of America.|Department of Biochemistry and Molecular Biology, School of Medicine, University of Miami, Coral Gables, Florida, 33136, United States of America.
Omaida C
OC
Velazquez
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D050091:Dendrimers; D019040:E-Selectin / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D018919:Neovascularization, Physiologic; D013234:Stem Cells / Q000166:cytology*; D014945:Wound Healing
D050091:Dendrimers; D019040:E-Selectin; C104700:PAMAM Starburst