Human embryonic stem cells (hESC) show great promise for tissue regeneration because of their propensity to make many of the cell types in the body. However, exactly how hESC can be directed to make specific parts of the body remains unclear. This is a major roadblock to harnessing the striking potential of hESC as a regenerative engineering solution for organ failure. Regeneration of complex tissues derived from the inner layer of the body called the endoderm such as the lung and pancreas is particularly challenging.
We already have in hand several novel hESC lines that have a strong propensity to enter endodermal tissues in small scale culture systems. We also have already enjoyed preliminary success with other kinds of stem cells in getting them to enter and make lung in special kinds of mice. Now we plan to see if we can make lung and pancreas with our new hESC lines.
Aim 1 We will try to force hESC to enter endoderm cell lineages by driving them with organ specific signals.
Aim 2. We will see how hESC do when they are introduced into developing lung or pancreas because we think there are special signals that come from naturally growing tissue.
Aim 3. We will see whether hESC can actually replace damaged lung or pancreatic tissue to simulate the repair of diseased tissue.
This project brings together an experienced team of investigators with complementary sets of expertise in hESC, tissue development, tissue repair and tissue regeneration. We expect to discover a toolbox of critical factors that will drive hESC to integrate into and function as part of endoderm derived tissues and hence are likely to directly bring forward hESC based regeneration solutions for failure of the lung and pancreas.
This work cannot be funded by the Federal Government because we will utilize novel hESC lines.
Statement of Benefit to California:
Diabetes and pulmonary failure are two serious and increasingly common problems among the children and adults of California. These serious public health problems lead to much loss of schooling and productivity every year. This proposal seeks to discover a toolbox of critical factors that will enable hESC to enter, integrate in and function as part of tissue regenerative solutions for lung and pancreatic failure. If we are successful, these critical factors may become medicines that will be critical to harnessing the potential of hESC as tissue regeneration solutions. The know-how for these critical processes will reside in California, giving the State a clear competitive advantage.