Lymphatic Reprogramming of Adult Endothelial Stem Cells for a Cell- Based Therapy for Lymphedema in Breast Cancer Patients

摘要

This research is designed to develop an efficient method to isolate and culture endothelial cell progenitor/stem cells from human adult blood and further to differentiate them into lymphatic lineage to be eventually used for cell-based therapy for post-operational lymphedema patients. The key significance of our proposal is to utilize the elusive circulating adult stem cells to avoid the ethical and immunological problems that the embryonic stem cell research faces. During the funding period, we made important progresses in isolation and culture of adult endothelial progenitor cells. In particular, we found that mononuclear cells from bloods displayed increased mitogenic potential in the endothelial cell basal medium that contains vascular endothelial cell growth factor (VEGF)-A and VEGF-C. Moreover, we found that addition of interleukin-3 activated the cells to upregulate Prox1, the master control gene for lymphatic development. However, we also found that adult endothelial progenitor cells failed to grow more than three passages under the current condition. We are currently investigating the optimal condition for the long term culture of these cells.