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Construction of Defined Human Engineered Cardiac Tissues to Study Mechanisms of Cardiac Cell Therapy
Published on: March 1, 2016
Review of stem cell-based therapy for the treatment of cardiovascular disease
1Department of Internal Medicine, University of Minnesota, 420 Delaware St. S.E. MMC 508, Minneapolis, MN 55455, USA. cmmartin@umn.edu
Insights
Cardiovascular disease, particularly heart failure, is a leading cause of death and significant healthcare cost. Stem cell therapies show promise for cardiac regeneration, with ongoing clinical trials exploring their effectiveness.
Area of Science:
- Regenerative Medicine
- Cardiology
- Stem Cell Biology
Background:
- Cardiovascular disease (CVD) is the leading cause of mortality in the US, with heart failure (HF) being a common end-stage condition.
- HF significantly impacts patient health outcomes, evidenced by a 20% 1-year mortality rate and substantial economic costs.
- Current treatments, including pharmacologic therapies and mechanical support, are limited, with heart transplantation being the only definitive option for advanced HF.
Purpose of the Study:
- To review the current state of cardiac regeneration research, focusing on stem cell-based therapies.
- To highlight advancements in preclinical animal studies and analyze the results of human clinical trials for HF treatment.
Main Methods:
- Review of preclinical animal studies investigating cardiac regeneration.
- Analysis of published human clinical trial data for stem cell therapies in various cardiovascular conditions.
- Evaluation of proposed mechanisms of cardiac regeneration, including direct differentiation and paracrine effects.
Main Results:
- The field of cardiac regeneration has rapidly advanced, with numerous cell types identified as potential candidates for repair.
- Conflicting results exist regarding the precise mechanisms of regeneration, with debates on cell differentiation versus paracrine signaling or cell fusion.
- Preclinical findings are being translated into human clinical trials for diverse cardiovascular diseases.
Conclusions:
- Stem cell-based therapies represent a promising alternative to heart transplantation for advanced heart failure, given the scarcity of donor organs.
- Further research is crucial to elucidate the exact mechanisms of cardiac regeneration and optimize therapeutic strategies.
- Ongoing clinical trials are essential to validate the efficacy and safety of stem cell treatments for cardiovascular diseases.
Abstract:
Cardiovascular disease remains the number one cause of mortality in the United States. Nearly 2,400 Americans die of cardiovascular disease each day, an average of 1 every 37 s. One in three Americans has been diagnosed with one or more forms of cardiovascular disease. Most recent estimates show that, in the United States alone, 16 million people have coronary artery disease and 5.3 million have been diagnosed with heart failure. Unlike other forms of cardiovascular disease, heart failure is often the end-stage of a cardiovascular disease, frequently coronary artery disease. The 1-year mortality of people diagnosed with heart failure remains a sobering 20%. Heart failure is also very costly. The estimated direct and indirect cost of heart failure in the US for 2008 is 34.8 billion dollars. Therefore, advanced treatment options for these populations could greatly impact patient health outcomes and cost savings. Even with the advancements in pharmacologic therapies and improvements in mechanical support devices, the only definitive treatment for advanced heart failure remains heart transplantation. Given the limited availability of donor organs for use in orthotopic heart transplantation, alternative therapies including stem cell-based therapies have been explored. The past decade has seen an explosion of activity of the field of cardiac regeneration. New scientific techniques and discoveries have allowed rapid advancements but there have also been conflicting opinions and results. The concept of cardiac regeneration is now commonly accepted but the exact mechanisms and extent of regeneration is greatly debated. Several candidate cell populations, both cardiac and extracardiac, have been reported to be capable of cardiac regeneration. However, some studies question if these cell populations actually differentiate into cardiomyocytes but rather function through paracrine effects or through cell fusion. Despite these challenges, the field has also begun translating the preclinical animal studies into human clinical trials using several cell types for the treatment of many clinical disease states. This review will highlight the preclinical animal studies and review the results of the published clinical trials.
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