Development of Advanced Cell-Based Therapy by Regulating Cell–Cell Interactions

Abstract

Cell-based therapy for disease treatment involves the transplantation of cells obtained either from self or others into relevant patients. While cells constituting the body tissues maintain homeostasis by performing remarkable functions through complicated cell–cell interactions, transplanted cells, which are generally cultured as a monolayer, are unable to recapitulate similar interactions in vivo. The regulation of cell–cell interactions can immensely increase the function and therapeutic effect of transplanted cells. This review aims to summarize the methods of regulating cell–cell interactions that could significantly increase the therapeutic effects of transplanted cells. The first method involves the generation of multicellular spheroids by three-dimensional cell culture. Spheroid formation greatly improved the survival and therapeutic effects of insulin-secreting cells in diabetic mice after transplantation. Moreover, mixed multicellular spheroids, composed of insulin-secreting cells and aorta endothelial cells or fibroblasts, were found to significantly improve insulin secretion. Secondly, adhesamine derivatives, which are low-molecular-weight compounds that accelerate cell adhesion and avoid anoikis and anchorage-dependent apoptosis, have been used to improve the survival of bone marrow-derived cells and significantly enhanced the therapeutic effects in a diabetic mouse model of delayed wound healing. Finally, the avidin-biotin complex method, a cell surface modification method, has been applied to endow tumor-homing mesenchymal stem cells with anti-tumor ability by modifying them with doxorubicin-encapsulated liposomes. The modified cells showed excellent effectiveness in cell-based cancer-targeting therapy. The discussed methods can be useful tools for advanced cell-based therapy, promising future clinical applications.