The Future of Cardiovascular Regenerative Medicine

Abstract

Regeneration of lost or injured tissues is very common in biology. Unfortunately, humans lack adequate regeneration in the heart and many other organs that are commonly ravaged by modern diseases. A revolution in stem cell biology has led to an explosion of interest in therapies that can awaken the regeneration potential in patients. In just the past decade, we have learned that any cell type from any patient, including cells from a blood sample or skin biopsies, can potentially be reprogrammed into a stem cell, and that patient’s stem cell can generate billions of new cells of a variety of differentiated cell types, including cardiomyocytes, endothelial cells and neurons. Stem cell biology is already changing how we approach human genetics and drug discovery, and clinical efforts to harness stem cell biology for heart failure are well underway. Here we predict that regenerative biology will initially struggle to hurdle economic and technical barriers for realistic treatments of heart diseases. However, regenerative biologists are beginning to design new approaches that were previously unimaginable, and ultimately regenerative medicine will have a profound impact for heart diseases.

Keywords: genetics; heart failure; pharmaceutical preparations.

Figure 1. Stem cell biology and reprogramming

While embryonic stem cell advances have enabled the generation of any cell type in the human body, the recognition that cells can be reprogrammed to other cells has opened the door to more diverse regenerative medicine approaches. Notably, fibroblasts can be directly converted to cardiomyocytes, without passing through a stem cell state.

Figure 2. Needs unmet by non-regenerative therapies will define regenerative medicine opportunities

Regenerative treatments will emerge but will be most useful in areas where more traditional approaches leave voids of unmet needs; thus, progress in other fields will play a major role in determining where regenerative breakthroughs can occur. However, stem cell biology will influence all approaches, by allowing testing and validation with human tissue of diverse genetic backgrounds.

Figure 3. Disease in a dish specific to individual patients

Even if most patients do not receive cellular therapies, regenerative biology will provide new testing platforms for therapy development. Generation of laboratory cells and tissues from specific patients provides the true genetic background of the disease. This approach is currently challenged by cost, time and reproducibility, but advances over the next decade will make this a routine approach for many diseases.

Figure 4. Gene editing to correct diseased cells

New technologies allow simple gene editing in stem cells, and this could enable unique approaches to many diseases. Stem cells from individual patients can be generated, with repair of one or even more genetic defects. The stem cells can then be directed to form cardiomyocytes or other types of cells, such as a hepatocyte with improved cholesterol metabolism. The cells with corrected function can be used to generate tissues for transplantation.

Figure 5. Regenerative medicine will drive integration

Achieving regeneration in patients will require integration of many skills. Most of these are obvious, but one particularly important integration step will be merging immunology with regenerative approaches.