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Sex hormones affect outcome in arrhythmogenic right ventricular cardiomyopathy/dysplasia: from a stem cell derived cardiomyocyte-based model to clinical biomarkers of disease outcome.

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Sex hormones affect outcome in arrhythmogenic right ventricular cardiomyopathy/dysplasia: from a stem cell derived cardiomyocyte-based model to clinical biomarkers of disease outcome.

Eur Heart J. 2017 Feb 18;:

Authors: Akdis D, Saguner AM, Shah K, Wei C, Medeiros-Domingo A, von Eckardstein A, Lüscher TF, Brunckhorst C, Chen HS, Duru F

Abstract
Aims: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is characterized by fibrofatty infiltration of the myocardium and ventricular arrhythmias that may lead to sudden cardiac death. It has been observed that male patients develop the disease earlier and present with more severe phenotypes as compared to females. Thus, we hypothesized that serum levels of sex hormones may contribute to major arrhythmic cardiovascular events (MACE) in patients with ARVC/D.
Methods and results: The serum levels of five sex hormones, sex hormone-binding globulin, high sensitivity troponin T, pro-brain natriuretic peptide, cholesterol, triglycerides, insulin, and glucose were measured in 54 ARVC/D patients (72% male). Twenty-six patients (48%) experienced MACE. Total and free testosterone levels were significantly increased in males with MACE as compared to males with a favourable outcome, whereas estradiol was significantly lower in females with MACE as compared to females with a favourable outcome. Increased testosterone levels remained independently associated with MACE in males after adjusting for age, body mass index, Task Force criteria, ventricular function, and desmosomal mutation status. Furthermore, an induced pluripotent stem cell-derived ARVC/D cardiomyocyte model was used to investigate the effects of sex hormones. In this model, testosterone worsened and estradiol improved ARVC/D-related pathologies such as cardiomyocyte apoptosis and lipogenesis, strongly supporting our clinical findings.
Conclusions: Elevated serum testosterone levels in males and decreased estradiol levels in females are independently associated with MACE in ARVC/D, and directly influence disease pathology. Therefore, determining the levels of sex hormones may be useful for risk stratification and may open a new window for preventive interventions.

PMID: 28329361 [PubMed - as supplied by publisher]

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Stem Cell Technology in Cardiac Regeneration: A Pluripotent Stem Cell Promise.

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Stem Cell Technology in Cardiac Regeneration: A Pluripotent Stem Cell Promise.

EBioMedicine. 2017 Feb;16:30-40

Authors: Duelen R, Sampaolesi M

Abstract
Despite advances in cardiovascular biology and medical therapy, heart disorders are the leading cause of death worldwide. Cell-based regenerative therapies become a promising treatment for patients affected by heart failure, but also underline the need for reproducible results in preclinical and clinical studies for safety and efficacy. Enthusiasm has been tempered by poor engraftment, survival and differentiation of the injected adult stem cells. The crucial challenge is identification and selection of the most suitable stem cell type for cardiac regenerative medicine. Human pluripotent stem cells (PSCs) have emerged as attractive cell source to obtain cardiomyocytes (CMs), with potential applications, including drug discovery and toxicity screening, disease modelling and innovative cell therapies. Lessons from embryology offered important insights into the development of stem cell-derived CMs. However, the generation of a CM population, uniform in cardiac subtype, adult maturation and functional properties, is highly recommended. Moreover, hurdles regarding tumorigenesis, graft cell death, immune rejection and arrhythmogenesis need to be overcome in clinical practice. Here we highlight the recent progression in PSC technologies for the regeneration of injured heart. We review novel strategies that might overcome current obstacles in heart regenerative medicine, aiming at improving cell survival and functional integration after cell transplantation.

PMID: 28169191 [PubMed - indexed for MEDLINE]

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Mesenchymal Stem Cells with eNOS Over-Expression Enhance Cardiac Repair in Rats with Myocardial Infarction.

Terapia celular - Hace 13 horas 37 mins
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Mesenchymal Stem Cells with eNOS Over-Expression Enhance Cardiac Repair in Rats with Myocardial Infarction.

Cardiovasc Drugs Ther. 2017 Feb;31(1):9-18

Authors: Chen L, Zhang Y, Tao L, Yang Z, Wang L

Abstract
PURPOSE: Transplantation of mesenchymal stem cells (MSCs) is a promising therapeutic option for patients with acute myocardial infarction.
METHODS: We show here that the ectopic overexpression of endothelial nitric oxide synthases (eNOS), an endothelial form of NOS, could enhance the ability of MSCs in treating ischemic heart damage after the occlusion of the coronary artery.
RESULTS: Adenoviral delivery of human eNOS gene into mouse bone marrow-derived MSCs (BM-MSCs) conferred resistance to oxygen glucose deprivation (OGD)-induced cell death in vitro, and elevated the bioavailability of nitric oxide when injected into the myocardium in vivo. In a rat model of acute myocardial infarction, the transplantation of eNOS-overexpressing BM-MSCs significantly reduced myocardial infarct size, corrected hemodynamic parameters and increased capillary density. We also found that the synergistic effects were consistently better than either treatment alone.
CONCLUSIONS: These findings reveal a positive role of elevated eNOS expression in cardiac repair, and suggest the combination of eNOS and MSC transplant therapy as a potential approach for treating myocardial infarction.

PMID: 27913896 [PubMed - indexed for MEDLINE]

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Miracle cells for natural dentistry - A review.

Terapia celular - Jue, 03/23/2017 - 00:54
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Miracle cells for natural dentistry - A review.

J Oral Biol Craniofac Res. 2017 Jan-Apr;7(1):49-53

Authors: Somani R, Jaidka S, Bajaj N, Arora S

Abstract
Stem cells are undifferentiated cells that can differentiate into specialized cells. Recently, enormous growth has been seen in the recognition of stem cell-based therapies, which have the potential to ameliorate the life of patients with conditions that span from Parkinson's disease to cardiac ischemia to bone or tooth loss. This research has produced new but unexplored possibilities in the regeneration of different organs and tissues. Presently, research is focused on the proficiency of stem cells and their utilization in dentistry, which is gaining interest. The tooth is nature's "esteem" for these precious stem cells and there are a number of these cells in permanent and primary teeth, as well as in the wisdom teeth. Dental stem cells are easy, convenient, and affordable to collect. They hold promise for a range of very potential therapeutic applications, such as in the treatment of cancer, spinal cord injury, brain damage, myocardial infarction, hearing loss, diabetes, wound healing, baldness, etc. Since these cells were used to regenerate damaged tissue in medical therapy successfully, it is possible that the dentist in future might use stem cell to regenerate lost or damaged dental and periodontal structures. This paper reviews the current concepts, characteristics of stem cells in regeneration, and its subsequent uses in dentistry.

PMID: 28316922 [PubMed - in process]

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stem cell myocardial regeneration; +934 new citations

Terapia celular - Mar, 03/21/2017 - 00:00

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