Stem cells can be transformed, or differentiated, into whatever cell the body instructs them to (e.g., bone or cartilage). Biologists have only begun to discover some of the specific chemicals that are used to direct the cells’ development into a given cell type. Our proposal provides a new method for rapidly screening reagents, which will enable us to develope new stem cell differentiating protocols. These new protocols are especially lacking in the area of human embryonic stem cells due to restrictions on federal funds. These protocols can be used by other scientist to enable new studies in other fields of biology and by physicians for regenerative medicinal treatment. This nanotechnology provides a new tool for growing tissue with multiple cell types. If successful, this will enable a new era in tissue engineering where complex functioning tissue can be created from stem cells. These man-made tissues include small blood vesicles for vascular grafts, skin for burn victims, bladder for bladder replacement surgery, and bone-cartaliage interface for treating arthritic patients.
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 vascular system is particularly challenging.
This work cannot be funded by the Federal Government because we will utilize novel hESC lines. 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 endothelial cells in vitro. Now we plan to apply our nanotechnology approach to provide a tissue engineering solution for making small blood vesicles
This project will bring together investigators who have extensive complimentary expertise in silicon nanotechnology, human embryonic stem cell biology, organogenesis, pathway analysis, and vascular biology. The experimental techniques described in this proposal lie at the cutting edge of both nanotechnology and human embryonic stem cell biology. They are straightforward extensions of our current capabilities and therefore represent feasible ideas that will produce results quickly. We believe there is unlimited potential for the cross-pollination of the two fields. By leveraging our extensive preliminary results and expertise, we expect to be able to discover a toolbox of critical factors that can direct the growth of hESC into endothelial precursors, which can then lead to the realization of hESC-derived vascular tissue for regenerative medicine.
Cardiovascular disease, including coronary artery and peripherical vascular disease (small and medium caliber arteries), is the leading cause of mortality in the United States each year and over 500,000 coronary artery bypass grafts are performed annually. Therapies for coronary artery and peripherical vascular diseases often require replacement of the diseased vessels with vascular grafts. Autologous arteries or veins are the best substitutes for small diameter (<6 mm) vessels. However, many patients do not have vessels suitable for grafting due to preexisting vascular diseases or vessel use in previous procedures. Therefore, many attempts have been made at engineering a small caliber arterial substitute that include endothelial cells (EC), smooth muscle cells (SMC), and/or fibroblasts on a variety of tubular scaffolds with limited success.
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 vascular grafting. 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 known-how and intellectual property generated by this research will reside in California, thus giving the state a competitive advantage over other states in area of stem cell research. The cumulative effect of scientific and newspaper publications and conference presentations will establish California as a focal point for future investments in this important emerging field.