Special Issue "Cell and Gene Therapy for Cardiac Repair"

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Cardiology".

Deadline for manuscript submissions: closed (20 April 2023) | Viewed by 5881

Special Issue Editor

Institute of Cardiology, Department of Surgical, Medical and Molecular Pathology and Critical Area Medicine, University of Pisa, 56124 Pisa, Italy
Interests: cell therapy; cardiac repair; gene therapy; exosomes; omics; pulmonary hypertension; cardiotoxicity; heart failure
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Special Issue Information

Dear Colleagues,

Ischemic heart disease (IHD) and end-stage heart failure are major causes of morbidity and mortality, and millions of IHD patients are treated by various medications, bypass surgery, or angioplasty around the world. Although treatment for acute myocardial infarction has improved over the past decades, including early reperfusion of occluded coronary arteries, novel therapeutic strategies are required to preserve cardiac function and improve clinical outcomes in patients with IHD. Additionally, new therapies are needed for the increased burden of chronic stages of heart failure. Transplantation of stem/progenitor cells has been considered as an alternative treatment for heart repair in both the acute and chronic phases of the disease. Although several issues have been raised from recent findings that stem cell therapy does not–or not yet in its current form–lead to muscle regeneration, some benefits have been observed. In fact, after the modest successes of the early clinical trials, research is now exploring the benefits of enhanced cell-based therapy and therapies with cell products.

This Special Issue will highlight recent advances in the context of cell therapy for cardiovascular disease.

Prof. Dr. Rosalinda Madonna
Guest Editor

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Keywords

  • Cell therapy
  • Cardiac repair
  • Myocardial ischemia
  • Mesenchymal stromal cells
  • Pluripotent stem cells

Published Papers (5 papers)

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Editorial

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Editorial
Exploring Enhanced Cell-Based Therapy for Ischemic Heart Disease and Heart Failure
J. Clin. Med. 2022, 11(13), 3837; https://doi.org/10.3390/jcm11133837 - 01 Jul 2022
Viewed by 612
Abstract
Ischemic heart disease (IHD) and heart failure (HF) remain the leading causes of death worldwide [...] Full article
(This article belongs to the Special Issue Cell and Gene Therapy for Cardiac Repair)

Research

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Article
Meta-Analysis of Percutaneous Endomyocardial Cell Therapy in Patients with Ischemic Heart Failure by Combination of Individual Patient Data (IPD) of ACCRUE and Publication-Based Aggregate Data
J. Clin. Med. 2022, 11(11), 3205; https://doi.org/10.3390/jcm11113205 - 04 Jun 2022
Cited by 4 | Viewed by 1365
Abstract
Individual patient data (IPD)-based meta-analysis (ACCRUE, meta-analysis of cell-based cardiac studies, NCT01098591) revealed an insufficient effect of intracoronary cell-based therapy in acute myocardial infarction. Patients with ischemic heart failure (iHF) have been treated with reparative cells using percutaneous endocardial, surgical, transvenous or intracoronary [...] Read more.
Individual patient data (IPD)-based meta-analysis (ACCRUE, meta-analysis of cell-based cardiac studies, NCT01098591) revealed an insufficient effect of intracoronary cell-based therapy in acute myocardial infarction. Patients with ischemic heart failure (iHF) have been treated with reparative cells using percutaneous endocardial, surgical, transvenous or intracoronary cell delivery methods, with variable effects in small randomized or cohort studies. The objective of this meta-analysis was to investigate the safety and efficacy of percutaneous transendocardial cell therapy in patients with iHF. Two investigators extracted the data. Individual patient data (IPD) (n = 8 studies) and publication-based (n = 10 studies) aggregate data were combined for the meta-analysis, including patients (n = 1715) with chronic iHF. The data are reported in accordance with PRISMA guidelines. The primary safety and efficacy endpoints were all-cause mortality and changes in global ejection fraction. The secondary safety and efficacy endpoints were major adverse events, hospitalization and changes in end-diastolic and end-systolic volumes. Post hoc analyses were performed using the IPD of eight studies to find predictive factors for treatment safety and efficacy. Cell therapy was significantly (p < 0.001) in favor of survival, major adverse events and hospitalization during follow-up. A forest plot analysis showed that cell therapy presents a significant benefit of increasing ejection fraction with a mean change of 2.51% (95% CI: 0.48; 4.54) between groups and of significantly decreasing end-systolic volume. The analysis of IPD data showed an improvement in the NYHA and CCS classes. Cell therapy significantly decreased the end-systolic volume in male patients; in patients with diabetes mellitus, hypertension or hyperlipidemia; and in those with previous myocardial infarction and baseline ejection fraction ≤ 45%. The catheter-based transendocardial delivery of regenerative cells proved to be safe and effective for improving mortality and cardiac performance. The greatest benefit was observed in male patients with significant atherosclerotic co-morbidities. Full article
(This article belongs to the Special Issue Cell and Gene Therapy for Cardiac Repair)
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Article
Advanced Glycation End Products Impair Cardiac Atrial Appendage Stem Cells Properties
J. Clin. Med. 2021, 10(13), 2964; https://doi.org/10.3390/jcm10132964 - 01 Jul 2021
Cited by 1 | Viewed by 1570
Abstract
Background: During myocardial infarction (MI), billions of cardiomyocytes are lost. The optimal therapy should effectively replace damaged cardiomyocytes, possibly with stem cells able to engraft and differentiate into adult functional cardiomyocytes. As such, cardiac atrial appendage stem cells (CASCs) are suitable candidates. However, [...] Read more.
Background: During myocardial infarction (MI), billions of cardiomyocytes are lost. The optimal therapy should effectively replace damaged cardiomyocytes, possibly with stem cells able to engraft and differentiate into adult functional cardiomyocytes. As such, cardiac atrial appendage stem cells (CASCs) are suitable candidates. However, the presence of elevated levels of advanced glycation end products (AGEs) in cardiac regions where CASCs are transplanted may affect their regenerative potential. In this study, we examine whether and how AGEs alter CASCs properties in vitro. Methods and Results: CASCs in culture were exposed to ranging AGEs concentrations (50 µg/mL to 400 µg/mL). CASCs survival, proliferation, and migration capacity were significantly decreased after 72 h of AGEs exposure. Apoptosis significantly increased with rising AGEs concentration. The harmful effects of these AGEs were partially blunted by pre-incubation with a receptor for AGEs (RAGE) inhibitor (25 µM FPS-ZM1), indicating the involvement of RAGE in the observed negative effects. Conclusion: AGEs have a time- and concentration-dependent negative effect on CASCs survival, proliferation, migration, and apoptosis in vitro, partially mediated through RAGE activation. Whether anti-AGEs therapies are an effective treatment in the setting of stem cell therapy after MI warrants further examination. Full article
(This article belongs to the Special Issue Cell and Gene Therapy for Cardiac Repair)
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Review

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Review
Cells and Materials for Cardiac Repair and Regeneration
J. Clin. Med. 2023, 12(10), 3398; https://doi.org/10.3390/jcm12103398 - 10 May 2023
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Abstract
After more than 20 years following the introduction of regenerative medicine to address the problem of cardiac diseases, still questions arise as to the best cell types and materials to use to obtain effective clinical translation. Now that it is definitively clear that [...] Read more.
After more than 20 years following the introduction of regenerative medicine to address the problem of cardiac diseases, still questions arise as to the best cell types and materials to use to obtain effective clinical translation. Now that it is definitively clear that the heart does not have a consistent reservoir of stem cells that could give rise to new myocytes, and that there are cells that could contribute, at most, with their pro-angiogenic or immunomodulatory potential, there is fierce debate on what will emerge as the winning strategy. In this regard, new developments in somatic cells’ reprogramming, material science and cell biophysics may be of help, not only for protecting the heart from the deleterious consequences of aging, ischemia and metabolic disorders, but also to boost an endogenous regeneration potential that seems to be lost in the adulthood of the human heart. Full article
(This article belongs to the Special Issue Cell and Gene Therapy for Cardiac Repair)
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Review
Vascular Progenitor Cells: From Cancer to Tissue Repair
J. Clin. Med. 2023, 12(6), 2399; https://doi.org/10.3390/jcm12062399 - 20 Mar 2023
Cited by 1 | Viewed by 586
Abstract
Vascular progenitor cells are activated to repair and form a neointima following vascular damage such as hypertension, atherosclerosis, diabetes, trauma, hypoxia, primary cancerous lesions and metastases as well as catheter interventions. They play a key role not only in the resolution of the [...] Read more.
Vascular progenitor cells are activated to repair and form a neointima following vascular damage such as hypertension, atherosclerosis, diabetes, trauma, hypoxia, primary cancerous lesions and metastases as well as catheter interventions. They play a key role not only in the resolution of the vascular lesion but also in the adult neovascularization and angiogenesis sprouting (i.e., the growth of new capillaries from pre-existing ones), often associated with carcinogenesis, favoring the formation of metastases, survival and progression of tumors. In this review, we discuss the biology, cellular plasticity and pathophysiology of different vascular progenitor cells, including their origins (sources), stimuli and activated pathways that induce differentiation, isolation and characterization. We focus on their role in tumor-induced vascular injury and discuss their implications in promoting tumor angiogenesis during cancer proliferation and migration. Full article
(This article belongs to the Special Issue Cell and Gene Therapy for Cardiac Repair)
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