Mending a broken heart: current strategies and limitations of cell-based therapy

Liew, Lee Chuen; Ho, Beatrice Xuan; Soh, Boon Seng

doi:10.1186/s13287-020-01648-0

Cited by 58 publications

(41 citation statements)

References 209 publications

(184 reference statements)

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“…Stem cell therapy effectively improves cardiac ejection fraction and reverse remodeling in heart failure ( 7 ), improves the survival rate, exercise capacity, and performance of patients with non-ischemic cardiomyopathy ( 8 ), and reduces the onset of refractory angina ( 9 ). However, the Efficacy and safety of stem cell therapy for heart diseases are unclarified, with potential risks of tumorigenicity, immunogenicity, and arrhythmia ( 10 ). Rigorously designed clinical trials are needed to prove the Efficacy of stem cell therapy in treating heart diseases and improve technology to reduce the related risks.…”

Section: Introductionmentioning

confidence: 99%

Cross-Sectional Survey of Clinical Trials of Stem Cell Therapy for Heart Disease Registered at ClinicalTrials.gov

Yang

Zhang

Liao

et al. 2021

Front. Cardiovasc. Med.

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Objective: It is important to register clinical trials before their implementation. There is a lack of study to evaluate registered clinical trials of stem cell therapy for heart diseases. Our study used the registration information at ClinicalTrials.gov to provide an overview of the registered trials investigating stem cell therapy for heart diseases.Methods: We searched ClinicalTrials.gov from inception to October 1, 2020 to identify clinical trials evaluating stem cell therapy for heart diseases. These trials were included in a cross-sectional survey and descriptive analysis. The outcomes included start date, completion date, location, status, study results, funding, phase, study design, conditions, interventions, sex, age, and sample size of those trials, as well as conditions, efficacy, safety and samples of the publications. SPSS 24.0 software was used for the statistical analysis.Results: A total of 241 trials were included. The registration applications for most trials originated from the United States, and the research start date ranged from 2001 to 2025. More than half of the trials have been completed, but few trials have published results (15.62%). The funding source for 81.12% of trials was recorded as “other” because the specific funding source was not indicated. There were 226 (93.78%) interventional studies and 15 (6.22%) observational studies; among all 241 studies, only 2.90% were phase 4 trials. Most interventional studies used randomized allocation, parallel assignment, and blinding. Of the observational studies, 6 were cohort studies (40.00%) and 73.33% were prospective. The most common disease was coronary artery disease (57.68%) and 98.34% included both male and female participants. The sample size included fewer than 50 patients in 58.51% of trials, and only 18 trials (7.47%) lasted more than 121 months. The registered details were illogical for nine trials (3.8%) that included 0 subjects and two trials (0.8%) that had a duration of 0 months (0.8%). In term of publications of the trials, most of the publications of the trials showed efficacy and safety in stem cell therapy for heart disease.Conclusion: The clinical trials investigating stem cell therapy for heart diseases registered at ClinicalTrials.gov are mostly interventional studies, and only a few are phase 4 trials. Most trials have a small sample size, and few have a duration of more than 121 months. Most of the completed trials did not publish their results, and some of the registration information was incomplete and illogical.

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Section: Introductionmentioning

confidence: 99%

Cross-Sectional Survey of Clinical Trials of Stem Cell Therapy for Heart Disease Registered at ClinicalTrials.gov

Yang

Zhang

Liao

et al. 2021

Front. Cardiovasc. Med.

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“…The emergence of induced pluripotent stem cell (iPSC) technologies is an additional cell source with therapeutic potential to treat HF. The major advantage of iPSC over other cell types for cell transplantation is that not only are the cells are patient-specific, thereby circumventing the important issue of tissue rejection associated with transplantation procedures, but they can also be differentiated into cardiac tissue [12]. Yet, despite the encouraging results from preclinical studies, a number of obstacles still need to be overcome before iPSC-based technology can be applied to animals for therapeutic purposes [13].…”

Section: Introductionmentioning

confidence: 99%

“…Principal limitations related to the use of iPSC-derived cardiac myocytes (iPSC-CMs) for regeneration include the heterogeneity of the cardiac cell types generated by the differentiation protocols and their lack of maturity [12]. Currently, all known differentiation protocols lead to a heterogeneous population of cells with varying proportions of atrial-, ventricular-, and nodal-like myocytes, as well as non-myocytes which, if implanted, are an arrhythmogenic risk [14,15].…”

Section: Introductionmentioning

confidence: 99%

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Optimizing the Use of iPSC-CMs for Cardiac Regeneration in Animal Models

Bizy

Klos

2020

Animals

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Heart failure (HF) is a common disease in which the heart cannot meet the metabolic demands of the body. It mostly occurs in individuals 65 years or older. Cardiac transplantation is the best option for patients with advanced HF. High numbers of patient-specific cardiac myocytes (CMs) can be generated from induced pluripotent stem cells (iPSCs) and can possibly be used to treat HF. While some studies found iPSC-CMS can couple efficiently to the damaged heart and restore cardiac contractility, almost all found iPSC-CM transplantation is arrhythmogenic, thus hampering the use of iPSC-CMs for cardiac regeneration. Studies show that iPSC-CM cultures are highly heterogeneous containing atrial-, ventricular- and nodal-like CMs. Furthermore, they have an immature phenotype, resembling more fetal than adult CMs. There is an urgent need to overcome these issues. To this end, a novel and interesting avenue to increase CM maturation consists of modulating their metabolism. Combined with careful engineering and animal models of HF, iPSC-CMs can be assessed for their potential for cardiac regeneration and a cure for HF.

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“…All these evidence suggest that despite the recent controversy, stem cell therapy is a promising therapy for regenerating the functional capacity of the diseased heart 14 – 16 . CPCs are involved in heart development, cell turnover, and endogenous repair following an injury to the heart, and hence are contenders as the ideal stem cell type 14 , 17 .…”

Section: Introductionmentioning

confidence: 99%

Combination of Cardiac Progenitor Cells From the Right Atrium and Left Ventricle Exhibits Synergistic Paracrine Effects In Vitro

et al. 2020

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Cardiovascular diseases, such as ischemic heart disease, remain the most common cause of death worldwide. Regenerative medicine with stem cell therapy is a promising tool for cardiac repair. Combination of different cell types has been shown to improve the therapeutic potential, which is thought to be due to synergistic or complimentary reparative effects. We investigated if the combination of cardiac progenitor cells (CPCs) of right atrial appendage (RAA) and left ventricle (LV) that are isolated from the same patient exert synergistic or complimentary paracrine effects for apoptotic cell death and angiogenesis in an in vitro model. Flow cytometry analysis showed that both RAA and LV CPCs expressed the mesenchymal cell markers CD90 and CD105, and were predominantly negative for the hematopoietic cell marker, CD34. Analysis of conditioned media (CM) collected from the CPCs cultured either alone or in combination in serum-deprived hypoxic conditions to simulate ischemia showed marked increase in the level of pro-survival hepatocyte growth factor and pro-angiogenic vascular endothelial growth factor-A in the combined RAA and LV CPC group. Next, to determine the therapeutic potential of CM, AC16 human ventricular cardiomyocytes and human umbilical vein endothelial cells (HUVECs) were treated with CM. Results showed a significant reduction in hypoxia-induced apoptosis of human cardiomyocytes treated with CM collected from combined RAA and LV CPC group. Similarly, matrigel assay showed a significantly increased tube length formed by HUVECs when treated with CM from combined RAA and LV CPC group. Our study provided evidence that the combination of RAA CPCs and LV CPCs may have superior therapeutic effects due to synergistic paracrine effects for cardiac repair. Therefore, in vivo studies are warranted to determine if a combination of different stem cell types have greater therapeutic potential than single-cell therapies.

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Mending a broken heart: current strategies and limitations of cell-based therapy

Cited by 58 publications

References 209 publications

Cross-Sectional Survey of Clinical Trials of Stem Cell Therapy for Heart Disease Registered at ClinicalTrials.gov

Cross-Sectional Survey of Clinical Trials of Stem Cell Therapy for Heart Disease Registered at ClinicalTrials.gov

Optimizing the Use of iPSC-CMs for Cardiac Regeneration in Animal Models

Combination of Cardiac Progenitor Cells From the Right Atrium and Left Ventricle Exhibits Synergistic Paracrine Effects In Vitro

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