Abstract

Despite considerable improvements in the treatment of cardiovascular diseases, heart failure (HF) still represents one of the leading causes of death worldwide. Poor prognosis is mostly due to the limited regenerative capacity of the adult human heart, which ultimately leads to left ventricular dysfunction. As a consequence, heart transplantation is virtually the only alternative for many patients. Therefore, novel regenerative approaches are extremely needed, and several attempts have been performed to improve HF patients’ clinical conditions by promoting the replacement of the lost cardiomyocytes and by activating cardiac repair. In particular, cell-based therapies have been shown to possess a great potential for cardiac regeneration. Different cell types have been extensively tested in clinical trials, demonstrating consistent safety results. However, heterogeneous efficacy data have been reported, probably because precise end-points still need to be clearly defined. Moreover, the principal mechanism responsible for these beneficial effects seems to be the paracrine release of antiapoptotic and immunomodulatory molecules from the injected cells. This review covers past and state-of-the-art strategies in cell-based heart regeneration, highlighting the advantages, challenges, and limitations of each approach.

Highlights

  • Cardiovascular diseases (CVDs) represent one of the leading causes of death in the world

  • Different cell types have been extensively tested in clinical trials, demonstrating consistent safety results

  • Acute myocardial infarction (AMI), a life-threatening condition resulting from a complete interruption of the blood flow to the heart [2], is considered one of the major components of CVDs, including nearly 580,000 new coronary attacks and 210,000 recurrent attacks every year in the United States [3]

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Summary

Introduction

Cardiovascular diseases (CVDs) represent one of the leading causes of death in the world. In the past 10 years, despite improvements and innovations in CVDs treatment, the number of patients diagnosed with HF increased by 23% [5], representing a challenging issue for both the scientific community and the health care systems. The estimated costs associated with HF management have globally reached 108 billion dollars per year [6] These statistics provide a perfect picture of the magnitude of the impact of chronic heart diseases (CHDs) on society, and the development of novel therapies is urgently warranted. Many HF patients are ineligible for heart transplantation because of concomitant comorbidities, and they remain without possible medical, surgical, or interventional treatment options [10] These are the main reasons why alternative regenerative approaches are extremely needed, and great effort has been directed by the scientific community for the past 25 years. In this review, we tried to provide an accurate analysis of the different cell-based regenerative strategies that have been proposed and developed, illustrating the pros and cons of each approach, drawing an overall picture of where we are today and where we are heading

Initial Studies with Committed Cells
Stem Cells
Embryonic Stem Cells
Adult Stem Cells
IC IM IM
Considerations on Cell Therapy
Findings
Conclusions
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