Research Focus: UCLA Cardiovascular Development and Regeneration Consortium

The revolution of regenerative medicine requires a team approach. Collaborations initiated with the Stem Cell Center's support are combining the expertise of basic, clinical, and translational scientists and are leading the way into the future of stem cell science.

The UCLA Cardiovascular Development and Regeneration Consortium (Consortium) is a multidisciplinary team of basic scientists and clinicians that successfully competed for a UCLA Broad Stem Cell Research Center Innovation Award to support their collaborative research using stem cells to regenerate heart tissue that will repair diseased or damaged hearts. The Consortium is led by Drs. Hanna Mikkola, associate professor of molecular, cell, and developmental biology, Reza Ardehali and Ali Nsair, both assistant professors of cardiology, and Atsushi Nakano, assistant professor of molecular, cell and developmental biology.

Research Goals
Heart disease is the leading cause of death worldwide. Heart tissue is difficult to develop and regenerate given its complex system of muscle, nerve, and blood cells. Until recently it was not thought viable to regenerate heart tissue. The Consortium’s effort is informed by a recent discovery by Dr. Mikkola’s laboratory indicating that progenitor cells from the lining of the heart (endocardium) can be used to generate the various cell types needed to regenerate healthy heart tissue. By capitalizing on this discovery, the team is directing these cells to become specific heart cells in hopes that they can be used to repair damage caused by heart attack or heart failure.

Innovation
A number of questions need to be answered before we can fully understand how to successfully integrate regenerated cells into a complex organ like the heart. The Consortium's collaborative research is the first to investigate the endocardium as a source of heart tissue progenitor cells. The team seeks to understand how cardiac progenitor cells form a diverse set of heart tissue through progressive specialization. They are using leading edge technology to track the cell lineage and analyze the progenitor cells during development to determine the utility of the cells for regenerating the necessary heart tissues.

To distinguish which progenitor cells develop the needed heart muscle cells and are therapeutically relevant, the Consortium seeks to identify novel surface markers, which are genes that appear on the cell surface, that can tell scientists if the progenitors will form many different cell types, or just a particular tissue type, such as the heart valves or the heart wall.

A View of the Future
The Consortium’s long-term goal is to evaluate the function of stem cell-derived heart muscle progenitor cells and how the cells integrate into a damaged heart. The group is now transplanting endocardia cells into preclinical models to evaluate engraftment, integration, and functional benefit. Through their work, the team hopes to create a platform for using stem cell-based therapies to treat heart damage and disease.

Together, the Consortium members’ collaborative efforts and complementary expertise are forming the foundation for translational and clinical advances, enabling human stem cells to be used for potential therapies and as tools for biomedical innovation. Their cutting-edge research is an example of the world-leading stem cell science in progress at the UCLA Broad Stem Cell Research Center and is driving basic discovery to the clinic.