$6 368 285
Tissues derived from stem cells can serve multiple purposes to enhance biomedical therapies. Human tissues engineered from stem cells hold tremendous potential to serve as better substrates for the discovery and development of new drugs, accurately model development or disease progression, and one day ultimately be used directly to repair, restore and replace traumatically injured and chronically degenerative organs. However, realizing the full potential of stem cells for regenerative medicine applications will require the ability to produce constructs that not only resemble the structure of real tissues, but also recapitulate appropriate physiological functions. In addition, engineered tissues should behave similarly regardless of the varying source of cells, thus requiring robust, reproducible and scalable methods of biofabrication that can be achieved using a holistic systems engineering approach. The primary objective of this research proposal is to create models of cardiac and neural human tissues from stem cells that can be used for various purposes to improve the quality of human health.
Statement of Benefit to California:
California has become internationally renowned as home to the world's most cutting-edge stem cell biology and a global leader of clinical translation and commercialization activities for stem cell technologies and therapies. California has become the focus of worldwide attention due in large part to the significant investment made by the citizens of the state to prioritize innovative stem cell research as a critical step in advancing future biomedical therapies that can significantly improve the quality of life for countless numbers of people suffering from traumatic injuries, congenital disorders and chronic degenerative diseases. At this stage, additional investment in integration of novel tissue engineering principles with fundamental stem cell research will enable the development of novel human tissue constructs that can be used to further the translational use of stem cell-derived tissues for regenerative medicine applications. This proposal would enable the recruitment of a leading biomedical engineer with significant tissue engineering experience to collaborate with leading cardiovascular and neural investigators. The expected result will be development of new approaches to engineer transplantable tissues from pluripotent stem cell sources leading to new regenerative therapies as well as an enhanced understanding of mechanisms regulating human tissue development.
Executive Summary The candidate principal investigator (PI) is an early to mid-career scientist leading an active research program focused on the interface of tissue engineering and stem cell biology. The proposed research emphasizes technologies to engineer three-dimensional (3D) multicellular aggregates that will model stem cell differentiation and morphogenesis processes. The PI has made numerous advances in designing novel culture systems that incorporate various bioengineering techniques. This proposal utilizes these approaches to develop transplantable 3D cardiac and neuronal tissues derived from human pluripotent stem cells (hPSCs). The candidate PI intends to promote the maturation of microscale 3D multicellular aggregates for use in regenerative medicine therapies. Research Vision and Plans - Reviewers were extremely enthusiastic about the candidate’s emphasis on a developmental biology-based approach (in lieu of a purely traditional engineering approach) for organ development. - The proposed research addresses several unmet needs in stem cell biology, including the control of purification and differentiation processes. - The proposed research represents a substantially vital step between the ability to generate specific cell types and the use of these cells in the repair of tissue damage. - Results from the proposed studies could help develop stem cell-based drug screening platforms and engineered tissues for heart and brain regeneration. - Reviewers viewed the integration of embryo extracellular matrix (ECM) components in 3D culture as important and innovative. - Reviewers suggested that Aim 3, with a focus on oxygen concentration effects on stem cell differentiation, should be developed more fully. PI Accomplishments and Potential - Reviewers praised the candidate PI as an excellent scientist who is integrating bioengineering and stem cell approaches. - Reviewers considered the candidate PI to be in the top tier of his/her field. - PI is one of the leaders in developing a set of innovative cell culture techniques for pluripotent stem cells. - The candidate has earned a high level of respect from scientific peers, who consider him/her to be a highly energetic scientist and a leader in the field. - The candidate PI’s training and letters of reference are exemplary. - The candidate has an excellent record of funding. - The PI has demonstrated high productivity, publishing a substantial number of articles; some reviewers noted that these primarily appeared in bioengineering journals rather than in high profile biology or biomedical journals. Institutional Commitment and Environment - This institutional commitment is very strong and includes adequate laboratory space, substantial start-up and equipment funds, and access to state-of-the-art core resources. -The institution investigators and resources are outstanding, and these provide an excellent environment for the proposed research. -Reviewers were excited by the complementary expertise of the candidate and other scientists at the institution and felt that this would provide great potential for innovation.