No abstract

In recent years, lymphangiogenesis, the process of lymphatic vessel formation from existing lymph vessels, has been demonstrated to have a significant role in diverse pathologies, including cancer metastasis, organ graft rejection, and lymphedema. Our understanding of the mechanisms of lymphangiogenesis has advanced on the heels of studies demonstrating vascular endothelial growth factor C as a central pro-lymphangiogenic regulator and others identifying multiple lymphatic endothelial biomarkers. Despite these breakthroughs and a growing appreciation of the signaling events that govern the lymphangiogenic process, there are no FDA-approved drugs that target lymphangiogenesis. In this review, we reflect on the lessons available from the development of antiangiogenic therapies (26 FDA-approved drugs to date), review current lymphangiogenesis research including nanotechnology in therapeutic drug delivery and imaging, and discuss molecules in the lymphangiogenic pathway that are promising therapeutic targets.

Living cells are extensively being studied to build functional tissues that are useful for both fundamental and applied bioscience studies. Increasing evidence suggests that cell-cell adhesion controlled by intercellular cadherin junction plays important roles in the quality of the resulting engineered tissue. These findings prompted efforts to interrogate biological effects of cadherin at a molecular scale; however, few efforts were made to harness the effects of cadherin on cells cultured in an in vivo-like three dimensional matrix. To this end, this study reports a hydrogel matrix three dimensionally functionalized with a controlled number of Fc-tagged recombinant N-cadherins (N-Cad-Fc). To retain the desired conformation of N-Cad, these cadherins were immobilized and oriented to the gel by anti-Fc-antibodies chemically coupled to gels. The gels were processed to present N-Cad-Fc in uniaxially aligned microchannels or randomly oriented micropores. Culturing cortical cells in the functionalized gels generated a large fraction of neurons that are functional as indicated by increased intracellular calcium ion concentrations with the microchanneled gel. In contrast, direct N-Cad-Fc immobilization to microchannel or micropore walls of the gel limited the growth of neurons and increased the glial to neuron ratio. The results of this study will be highly useful to organize a wide array of cadherin molecules in a series of biomaterials used for three-dimensional cell culture and to regulate phenotypic activities of tissue-forming cells in an elaborate manner.