The first report describing LQTS type 1 patient-specific iPSC-CMs demonstrated that the cells were able to recapitulate the electrophysiological properties of the disorder: they exhibited ...prolongation of action potential duration, altered Iks activation and deactivation properties, and abnormal response to catecholamine stimulation that was prevented by beta-blockers (8). iPSC-CMs derived from patients affected by LQTS type 2 displayed significant prolongation of the action potential duration due to significant reduction of the Ikr current (9). ...it is worth noting the urgent need for standardization of the parameters that define iPSCs in general, and iPSC-CMs in particular, to facilitate the comparison between the results obtained by different groups.
We report the generation of human induced pluripotent stem cells (hiPSCs) from dermal fibroblasts of a female patient carrier of the two compound heterozygous mutations c.568 C>T p.R190W (maternal ...allele), and c.1781 G>A p.R594Q (paternal allele) on the KCNQ1 gene, causing Jervell and Lange-Nielsen Syndrome (JLNS). To obtain hiPSCs, we used the classical approach of the four retroviruses each encoding for a reprogramming factor OCT4, SOX2, KLF4, cMYC. The obtained hiPSC clones display pluripotent stem cell characteristics, and differentiate into spontaneously beating cardiomyocytes (hiPSC-CMs).
Abstract Mesenchymal stem cells (MSC) are adult stem cells with capacity for self-renewal and multi-lineage differentiation. Initially described in the bone marrow, MSC are also present in other ...organs and tissues. From a therapeutic perspective, because of their easy preparation and immunologic privilege, MSC are emerging as an extremely promising therapeutic agent for tissue regeneration and repair. Studies in animal models of myocardial infarction have demonstrated the ability of transplanted MSC to engraft and differentiate into cardiomyocytes and vascular cells. Most importantly, engrafted MSC secrete a wide array of soluble factors that mediate beneficial paracrine effects and may greatly contribute to cardiac repair. Together, these properties can be harnessed to both prevent and reverse remodeling in the ischemically injured ventricle. In proof-of-concept and phase I clinical trials, MSC therapy improved left ventricular function, induced reverse remodeling, and decreased scar size. In this review we will focus on the current understanding of MSC biology and MSC mechanism of action in cardiac repair.
The development of human induced pluripotent stem cell (iPSC) technology has revitalized the efforts made in the last decade to exploit the potential of human embryonic stem cells (ESCs) for ...scientific research. In the field of cardiac arrhythmias, the possibility of generating an unlimited amount of patient-specific cardiomyocyte-like cells (iPSC-CMs) has clear advantages compared with the use of ESC-derived cardiac cells. In particular, with the introduction and implementation of the large-scale precision medicine initiative, we anticipate that the iPSC technology will play an important role in the advancement of cardiovascular research and medicine. This platform is not free from technical limitations that must be carefully taken into account; however, the utility of iPSC-CMs in disease modeling and drug testing studies is hardly questionable.
Here, we summarize some of the progresses made in the field of iPSC technology applied to inherited cardiac arrhythmias, with particular emphasis on the use of iPSC-CMs for modelling the long QT syndrome and for the development of personalized drug and molecular therapies. The growing role of iPSC technology in the practice of precision medicine will also be discussed.
Abstract
Aims
To evaluate the impact of the COVID-19 pandemic on patient admissions to Italian cardiac care units (CCUs).
Methods and Results
We conducted a multicentre, observational, nationwide ...survey to collect data on admissions for acute myocardial infarction (AMI) at Italian CCUs throughout a 1 week period during the COVID-19 outbreak, compared with the equivalent week in 2019. We observed a 48.4% reduction in admissions for AMI compared with the equivalent week in 2019 (P < 0.001). The reduction was significant for both ST-segment elevation myocardial infarction STEMI; 26.5%, 95% confidence interval (CI) 21.7–32.3; P = 0.009 and non-STEMI (NSTEMI; 65.1%, 95% CI 60.3–70.3; P < 0.001). Among STEMIs, the reduction was higher for women (41.2%; P = 0.011) than men (17.8%; P = 0.191). A similar reduction in AMI admissions was registered in North Italy (52.1%), Central Italy (59.3%), and South Italy (52.1%). The STEMI case fatality rate during the pandemic was substantially increased compared with 2019 risk ratio (RR) = 3.3, 95% CI 1.7–6.6; P < 0.001. A parallel increase in complications was also registered (RR = 1.8, 95% CI 1.1–2.8; P = 0.009).
Conclusion
Admissions for AMI were significantly reduced during the COVID-19 pandemic across Italy, with a parallel increase in fatality and complication rates. This constitutes a serious social issue, demanding attention by the scientific and healthcare communities and public regulatory agencies.
Investigations showed raised high-sensitivity cardiac troponin I (9449 ng/L), creatine phosphokinase (671·0 U/L), C-reactive protein (32·5 mg/L), and lactate dehydrogenase (276·0 U/L) concentrations ...(appendix). The leucocyte count was 12·75 × 109 per L, the neutrophil count was 10·04 × 109 per L, and the lymphocyte count was 0·78 × 109 per L. We gave the boy aspirin to relieve his pain and transferred him to the coronary care unit with a working diagnosis of acute myocarditis. Paediatric patients reporting chest pain and other features suggestive of acute myocarditis—with or without respiratory symptoms—should, we believe, also be tested for SARS-CoV-2 (video).
Long COVID has become a world-wide, non-communicable epidemic, caused by long-lasting multiorgan symptoms that endure for weeks or months after SARS-CoV-2 infection has already subsided. This ...scientific document aims to provide insight into the possible causes and therapeutic options available for the cardiovascular manifestations of long COVID. In addition to chronic fatigue, which is a common symptom of long COVID, patients may present with chest pain, ECG abnormalities, postural orthostatic tachycardia, or newly developed supraventricular or ventricular arrhythmias. Imaging of the heart and vessels has provided evidence of chronic, post-infectious perimyocarditis with consequent left or right ventricular failure, arterial wall inflammation, or microthrombosis in certain patient populations. Better understanding of the underlying cellular and molecular mechanisms of long COVID will aid in the development of effective treatment strategies for its cardiovascular manifestations. A number of mechanisms have been proposed, including those involving direct effects on the myocardium, microthrombotic damage to vessels or endothelium, or persistent inflammation. Unfortunately, existing circulating biomarkers, coagulation, and inflammatory markers, are not highly predictive for either the presence or outcome of long COVID when measured 3 months after SARS-CoV-2 infection. Further studies are needed to understand underlying mechanisms, identify specific biomarkers, and guide future preventive strategies or treatments to address long COVID and its cardiovascular sequelae.
The development and production of cell gene and tissue (CGT)-based therapies requires a specialized workforce. Entering the CGT arena is complex because it involves different scientific and ...biomedical aspects (e.g., immunology, stem cell biology and transplantation), as well as knowledge of regulatory affairs and compliance with pharmaceutical quality standards. Currently, both industry and academia are facing a worldwide workforce shortage, whereas only a handful of educational and training initiatives specifically address the peculiarities of CGT product development, the procurement of substances of human origin, the manufacturing process itself and clinical monitoring and biovigilance. The training offered by traditional Master's and PhD programs is not suited for training a skilled workforce ready to enter the increasingly fast-growing CGT field. Indeed, typically these programs are of long duration and only partially cover the required competencies, whereas the demand for a specialized workforce relentlessly increases. In this paper, we (i) present and discuss our understanding of the roots of current growth acceleration of the CGT field; (ii) anticipate future workforce needs due to the expected increase of marketed CGT-based therapies and (iii) evaluate potential solutions that seek to adapt, develop and implement current educational and training initiatives. Importantly for these solutions, we call for scientific societies, such as the International Society for Cell & Gene Therapy, to play a more active role and act as catalysers for new initiatives, building bridges between academia and Industry to establish effective educational and training programs that will engage and prepare a new generation of qualified professionals for entry into the CGT field.
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