Human pluripotent stem cells (hPSCs) and their derivatives represent the only research tool to study human development. As such, these cells allow us to study the progression of diseases at the cellular level in a dish, probe how specific genetic defects contribute to the myriad of developmental and birth defects, and generate the “raw material” for the development of cell-based therapies of presently incurable diseases, such as cancer, cardiovascular disease, and neurodegenerative disorders. However, our understanding of the basic mechanisms underlying stem cell biology is incomplete, and the processes by which individual cells organize each other to give rise to the complexity of multi-cellular life remain mysterious.
At the heart of embryonic development, and hence stem cell biology, lies an intricate process of cell communication. Individual cells produce and release signals, known as growth factors, that instruct neighboring cells to assume specific behaviors and properties. Wnt proteins represent a major class of growth factors with potent effects on stem cells and developmental processes. We have examined the role of these Wnt proteins in hPSCs and their derivatives, including neural stem cells, a cell type that can generate many of the cells found in the central nervous system. The goal of this research project was to gain a better understanding of these WNT growth factors so that we can apply them to affect stem cell behavior. Identifying the mechanisms by which Wnt proteins act has allowed us to contribute valuable tools and protocols for the manipulation of hPSC and neural stem cells into mature cell types suitable for cell replacement therapies and disease modeling.
With a rise in life expectancy to over 80 years an increased number of people are suffering from age-related diseases, such as cancer and neurodegenerative disorders. Current medical treatments do not cure such diseases. Recent advances in the study of hPSCs have provided the opportunity to develop novel cell replacement therapies for the treatment of many such diseases. Development of novel cell-based therapies will also overcome the inadequacy of conventional drug-based treatments. A major challenge in the study and use hPSCs is to develop robust methods for the directed differentiation of hPSC into functionally mature cell types suitable for therapeutic applications. Our research has been aimed at gaining a better understanding of how to manipulate hPSCs and neural stem cells. The research has led to fundamental insights into hPSC biology and produced protocols and reagents of critical importance in regenerative medicine. In addition, this research has broad benefits to sceintists with a wide spectrum of interests. The research has provided not only the foundation for the scientific advances in regenerative medicine to improve health, but also technology advancement and financial profit for the people of California.