Mobilization of Notch ligand to a poly-HEMA scaffold to promote thymopoiesis and model T cell development (58.19)

Abstract

Notch signaling is critical for thymopoiesis. Notch ligand’s expression on thymic epithelial cells is crucial to the development naïve T lymphocytes and therefore characterized as one of the primary signaling pathways. We are developing a biomaterial-based model of thymopoiesis. We hypothesize that by binding the Notch ligand onto a biomaterial based scaffold, we can maintain the Notch ligand in its active form, and differentiate mouse embryonic stem cells into T-lymphocytes. The common protocol for differentiating mouse embryonic stem cells into T lymphocytes is using the OP9 system. In this system, the stem cells are supported by a monolayer of stromal cells that express the Notch ligand on its surface. Our project aims to bypass the monolayer of living cells and replace them with a biocompatible inorganic matrix that provides the cells with the necessary environment to differentiate into T lymphocytes. We are currently using Poly(2-hydroxyethyl methacrylate) which is both biocompatible and has a similar Young’s modulus of the lymph nodes, which also expresses Notch. We have confirmed activation of the ligand through ELISA and are in the process of differentiating the embryonic stem cells. This project holds significant implications for the field on immunology. If successful, this early prototype can become the basis of the first artificial thymus.