Targeted Bone Marrow Cell Delivery Mediated By Nanocarriers Endowed With Molecular Recognition

Introduction: 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. Methods: We have developed 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. Wound healing was measured by digital photograph and ImageJ calculation. Targeted tissue homing of LacZ + bone marrow cells (BMC) was detected and quantified by X-gal staining, and BMC-enhanced neovascularization was examined by Dil perfusion and scanning confocal microscopy. Results: Soluble E-selectin (sE-sel) was successful installed on BMC surface by dendrimer nanocarriers. sE-sel-nanocarriers can associate with E-selectin ligands highly expressed on the wound endothelium, by which coated BMC are targeted delivered to skin wound tissues and grafted corneas to promote wound healing and neovascularization. Conclusions: We demonstrate feasibility, efficacy and safety of our targeted nanocarrier for delivery of 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.