Skeletal muscle metabolism after stroke: a comparative study using treadmill and overground walking test

Objective: The primary aim of this study was to investigate muscle metabolism in stroke survivors through measurements of the respiratory exchange ratio and rates of fat and carbohydrate oxidation in relation to total energy expenditure at preferred walking speed during treadmill and overground walking. The secondary objective was to investigate whether the energy source used during walking influences the daily physical activity pattern and fatigue of post-stroke individuals. Methods: The sample comprised 28 stroke participants and 10 non-disabled, healthy controls. Measurements of oxygen consumption and carbon dioxide production were recorded. Participants wore a uniaxial accelerometer (activPAL™) over 4 days as an estimate of daily physical activity. Measurements of Human Activity Profile and Neurological Fatigue Index for stroke were documented. Results: Carbohydrate oxidation accounted for the majority of fuel oxidation at preferred walking speed in the stroke group (55.86% vs 47.29% during tread-mill walking and 66.13% vs 50.15% during overground walking). Stroke patients who had higher levels of carbohydrate oxidation reached a lower score in the Human Activity Profile survey, had fewer steps screened by activPAL data (4,422 vs 6,692 steps/day) and higher fatigue index. Conclusion: Carbohydrate oxidation accounted for the majority of fuel oxidation at the preferred walking speed in post-stroke individuals. The increased carbohydrate utilization recorded at preferred walking speed may have influenced the physical activity profile

Stem cell death and survival in heart regeneration and repair

Cardiovascular diseases are major causes of mortality and morbidity. Cardiomyocyte apoptosis disrupts cardiac function and leads to cardiac decompensation and terminal heart failure. Delineating the regulatory signaling pathways that orchestrate cell survival in the heart has significant therapeutic implications. Cardiac tissue has limited capacity to regenerate and repair. Stem cell therapy is a successful approach for repairing and regenerating ischemic cardiac tissue; however, transplanted cells display very high death percentage, a problem that affects success of tissue regeneration. Stem cells display multipotency or pluripotency and undergo self-renewal, however these events are negatively influenced by upregulation of cell death machinery that induces the significant decrease in survival and differentiation signals upon cardiovascular injury. While efforts to identify cell types and molecular pathways that promote cardiac tissue regeneration have been productive, studies that focus on blocking the extensive cell death after transplantation are limited. The control of cell death includes multiple networks rather than one crucial pathway, which underlies the challenge of identifying the interaction between various cellular and biochemical components. This review is aimed at exploiting the molecular mechanisms by which stem cells resist death signals to develop into mature and healthy cardiac cells. Specifically, we focus on a number of factors that control death and survival of stem cells upon transplantation and ultimately affect cardiac regeneration. We also discuss potential survival enhancing strategies and how they could be meaningful in the design of targeted therapies that improve cardiac function

Fluorescence properties of curcumin-loaded nanoparticles for cell tracking

Bassam Felipe Mogharbel,1 Julio Cesar Francisco,1 Ana Carolina Irioda,1 Dilcele Silva Moreira Dziedzic,1 Priscila Elias Ferreira,1 Daiany de Souza,1 Carolina Maria Costa de Oliveira Souza,1 Nelson Bergonse Neto,2 Luiz Cesar Guarita-Souza,2 Celia Regina Cavichiolo Franco,3 Celso Vataru Nakamura,4 Vanessa Kaplum,4 Letícia Mazzarino,5 Elenara Lemos-Senna,6 Redouane Borsali,7 Paula A Soto,8 Patricia Setton-Avruj,8 Eltyeb Abdelwahid,9 Katherine Athayde Teixeira de Carvalho1 1Cell Therapy and Biotechnology in Regenerative Medicine Department, Pelé Pequeno Príncipe Institute, Child and Adolescent Health Research and Pequeno Príncipe Faculty, Curitiba, Paraná, Brazil; 2Institute of Biological and Health Sciences, Pontifical Catholic University of Paraná (PUCPR), Centro de Ciências Biológicas e da Saúde (CCBS), Curitiba, Brazil; 3Cell Biology Department, Federal University of Paraná, Curitiba, Paraná, Brazil; 4Department of Pharmaceutical Sciences, Universidade Estadual de Maringá, Maringá, Paraná, Brazil; 5Department of Pharmaceutical Sciences, NanoBioMat Laboratory, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil; 6Department of Pharmaceutical Sciences, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil; 7Centre de Recherches sur les Macromolécules Végétales (CERMAV), Centre National de la Recherche Scientifique (CNRS), University Grenoble Alpes, F-38000, Grenoble, France; 8Instituto de Química y Físicoquímica Biológica (IQUIFIB), Departament of Química Biológica, Facultad de Farmacia y Bíoquímica, Universidad de Buenos Aires (UBA) Consejo nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentine; 9Feinberg School of Medicine, Feinberg Cardiovascular Research Institute, Northwestern University, Chicago, Il, USA Background: Posttransplant cell tracking, via stem cell labeling, is a crucial strategy for monitoring and maximizing benefits of cell-based therapies. The structures and functionalities of polysaccharides, proteins, and lipids allow their utilization in nanotechnology systems. Materials and methods: In the present study, we analyzed the potential benefit of curcumin-loaded nanoparticles (NPC) using Vero cells (in vitro) and NPC-labeled adipose-derived mesenchymal stem cells (NPC-ADMSCs) (in vivo) in myocardial infarction and sciatic nerve crush preclinical models. Thereafter, transplantation, histological examination, real time imaging, and assessment of tissue regeneration were done. Results: Transplanted NPC-ADMSCs were clearly identified and revealed potential benefit when used in cell tracking. Conclusion: This approach may have broad applications in modeling labeled transplanted cells and in developing improved stem cell therapeutic strategies. Keywords: mesenchymal stem cells, transplantation, cell marking, myocardium infarction, sciatic nerve crus

Chapter 11: Regenerative Medicine and Biomarkers for Dilated Cardiomyopathy

Dilated cardiomyopathy is characterized by progressive cardiomyocyte loss leading to ventricle dilation and dysfunction. Over the last decade, multiple evidence has shown that treatment of this condition might be attempted through the administration of either cells of various derivations or nucleic acids. In the case of cell therapy, there is ample consensus that no stem cells can directly regenerate the myocardium; however some cell types could provide benefit through a paracrine function on resident cardiomyocytes. Various nucleic acids, including microRNAs and antisense locked nucleic acids targeting microRNAs and long non-coding RNAs, can stimulate regeneration by promoting the proliferation potential of endogenous cardiomyocytes. Albeit at the preclinical phase, these approaches hold a great promise for the development of innovative therapeutics. Patients with idiopathic dilated cardiomyopathy are generally young subjects. Therefore, the assessment of prognosis is essential. Biomarkers are nowadays widely available and are useful tools for risk stratification. Besides HF-dedicated biomarkers, such as natriuretic peptides, galectin-3, soluble ST2 and troponins, also the evaluation of inflammatory response (interleukins, growth factors), renal function (NGAL, KIM-1) and anaemia are particularly important for a correct prognostic stratification. Moreover, when all of these biomarkers are used and combined in a multimarker model, the prediction of prognosis becomes more accurate, reflecting the importance of a holistic evaluation of patients

Current status and perspectives of cell therapy in Chagas disease

One century after its discovery, Chagas disease, caused by the protozoan, Trypanosoma cruzi, remains a major health problem in Latin America. Mortality and morbidity are mainly due to chronic processes that lead to dysfunction of the cardiac and digestive systems. About one third of the chronic chagasic individuals have or will develop the symptomatic forms of the disease, with cardiomyopathy being the most common chronic form. This is a progressively debilitating disease for which there are no currently available effective treatments other than heart transplantation. Like in other cardiac diseases, tissue engineering and cell therapy have been investigated in the past few years as a means of recovering the heart function lost as a consequence of chronic damage caused by the immune-mediated pathogenic mechanisms elicited in individuals with chronic chagasic cardiomyopathy. Here we review the studies of cell therapy in animal models and patients with chronic Chagas disease and the perspectives of the recovery of the heart function lost due to infection with T. cruzi