XANADU como medio de expansión químicamente definido para células madre mesenquimales humanas derivadas de tejido adiposo

Las células madre mesenquimales humanas (CMMh) derivadas de tejido adiposo tienen características y propiedades que las hacen atractivas para la medicina regenerativa. Para ser llevadas a clínica estas células deben ser cultivadas en condiciones de Buenas Prácticas de Fabricación y los medios químicamente definidos son los ideales para mantener estas condiciones por su composición definida libre de elementos xenogénicos. El objetivo del presente trabajo fue evaluar el medio químicamente definido XANADU como medio de expansión a largo plazo para CMMh en comparación con un medio suplementado con suero fetal bovino (medio control) y un medio comercial químicamente definido (MQD-Comercial). La cinética de crecimiento fue evaluada a lo largo de 8 pases (56 días). La morfología y adherencia al plástico fue evaluada visualmente por microscopía. Se midieron la presencia de marcadores específicos de CMMh: presencia de CD73, CD90 y CD105, y ausencia de CD45, CD34 y HLA-DR. Se realizaron ensayos de diferenciación hacia condroblasto, adipocito y osteoblasto. Se evaluó la capacidad de la inmunosupresión del secretoma de las CMMh y la expresión de marcadores de potencial de diferenciación: FABP4, RUNX2, SOX9; de capacidad de inmunomodulación: IL-10, IDO, CXCL9, CXCL10; de migración y homing: CXCR4 y reguladores del ciclo celular: p21, p53, pRb. Además, se evaluó la estabilidad cromosómica mediante un análisis de cariotipo. En todos los experimentos el medio XANADU logró mantener o mejorar significativamente (p<0,05) el perfil de las CMMh expandidas en relación al medio control y el MQD-Comercial. Durante los 8 pases analizados XANADU, en relación al medio control, mantuvo un tiempo de duplicación significativamente menor entre 45 y 70 horas, similar expresión de marcadores de CMMh y capacidad de diferenciación. Además, la capacidad de inmunosupresión del secretoma de las CMM en medio XANADU fue significativamente mayor al MQDComercial. En torno a la expresión génica el medio XANADU aumento significativamente la expresión de los marcadores de potencial de diferenciación, los antiinflamatorios: IL-10, IDO y el quimiorreceptor CXCR4; mientras que mantuvo la expresión de los marcadores proinflamatorios CXCL9 y CXCL10 y los marcadores de regulación del ciclo celular similares al control. Además, las células expandidas en medio XANADU no presentaron aberraciones cromosómicas. En conclusión, el medio químicamente definido XANADU es un medio de expansión que mejora las propiedades y características de las CMMh, que las hacen relevantes para su uso en ensayos clínicos.Perú. Consejo Nacional de Ciencia y Tecnología. Fondo Nacional de Desarrollo Científico y Tecnológico (Fondecyt). Banco Mundial. Contrato Nº 09- 2019-FONDECYT-BM-INC.IN

Importancia de la genética como ciencia en relación a la pandemia de COVID-19: Importance of genetics as a science in relation to the COVID-19 pandemic

The current COVID-19 pandemic has become a major global public health problem with almost one and a half million cases and tens of thousands of deaths until now. Genetics is playing a leading role in the identification, management and treatment of diseases. This article details the importance of genetics as a science to face the global threat of COVID-19, from different approaches. The contributions that genetics have had and will continue to have in the identification of the new SARS-CoV-2 virus, in the development of new diagnostic techniques, in the prevention of infections and development of severe symptoms, as well as in the design of vaccines and in the proposal and evaluation of treatments for COVID-19.La actual pandemia de COVID-19 se ha convertido en un grave problema de salud pública mundial, contándose casi un millón y medio de casos y decenas de miles de muertes a la fecha. La genética por su parte está teniendo un papel protagónico en la identificación, manejo y tratamiento de enfermedades. En el presente artículo se detalla sobre la importancia de la genética como ciencia para afrontar la amenaza global de la COVID-19, desde diferentes enfoques. Se resaltan los aportes que ha tenido y seguirá teniendo la genética en la identificación del nuevo virus SARS- CoV-2, en el desarrollo de nuevas técnicas diagnósticas, en la prevención de contagios y del desarrollo de cuadros graves, así como en el diseño de vacunas y en la propuesta y evaluación de tratamientos para la COVID-19

Mesenchymal Stromal Cell-Based Therapies as Promising Treatments for Muscle Regeneration After Snakebite Envenoming

Snakebite envenoming is a global neglected disease with an incidence of up to 2.7 million new cases every year. Although antivenoms are so-far the most effective treatment to reverse the acute systemic effects induced by snakebite envenoming, they have a limited therapeutic potential, being unable to completely neutralize the local venom effects. Local damage, such as dermonecrosis and myonecrosis, can lead to permanent sequelae with physical, social, and psychological implications. The strong inflammatory process induced by snake venoms is associated with poor tissue regeneration, in particular the lack of or reduced skeletal muscle regeneration. Mesenchymal stromal cells (MSCs)-based therapies have shown both anti-inflammatory and pro-regenerative properties. We postulate that using allogeneic MSCs or their cell-free products can induce skeletal muscle regeneration in snakebite victims, improving all the three steps of the skeletal muscle regeneration process, mainly by anti-inflammatory activity, paracrine effects, neovascularization induction, and inhibition of tissue damage, instrumental for microenvironment remodeling and regeneration. Since snakebite envenoming occurs mainly in areas with poor healthcare, we enlist the principles and potential of MSCs-based therapies and discuss regulatory issues, good manufacturing practices, transportation, storage, and related-procedures that could allow the administration of these therapies, looking forward to a safe and cost-effective treatment for a so far unsolved and neglected health problem.The authors are supported by the University Pablo de Olavide (Sevilla), the University Miguel Hernández (Elche, Alicante), National University Toribio Rodriguez de Mendoza (Chachapoyas, Peru) Grants: Contrato N° 09-2019-FONDECYT-BM-INC.INV to JRT, JDRF 2-SRA-2019-837-S-B and AVI-GVA COVID-19-68 to BS, Fundación Andaluza de I+D and Al-Andalus Biopharma Project (FAID-2018-1). The authors CC-O, CG-D, and TCSA were supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil (CNPq) (Process: 406163/2018-9), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazil - CAPES (Program COFECUB Process: 88881.191812/2018-01) and by Fundação de Amparo à Pesquisa do Estado de Minas Gerais, Brazil (FAPEMIG)

Epidemiological Analysis of COVID-19 Cases in Native Amazonian Communities from Peru

Despite early control measures, SARS-CoV-2 reached all regions of Peru during the first wave of the pandemic, including native communities of the Peruvian Amazon. Here, we aimed to describe the epidemiological situation of COVID-19 in the Amazonas region of Peru using an open database of 11,124 COVID-19 cases reported from 19 March to 29 July 2020, including 3278 cases from native communities. A high-incidence area in northern Amazonas (Condorcanqui) reported a cumulative incidence of 63.84/1000 inhabitants with a much lower death rate (0.95%) than the national average. Our results showed at least eight significant factors for mortality, and the Native Amazonian ethnicity as a protective factor. Molecular confirmatory tests are necessary to better explain the high incidence of antibody response reported in these communities

Malaria y COVID-19 en comunidades nativas de Amazonas, Perú: Malaria and COVID-19 in native communities of Amazonas, Peru

Introduction In recent years, the number of malaria cases in native communities from Condorcanqui, Amazonas has considerably increased. Plasmodium vivax malaria is endemic in the region and the re-introduction of P. falciparum was reported in 2019. Methods Here, we compiled and analyzed malaria and COVID-19 data reported by the Regional Direction of Health (DIRESA) during the 2020. Additionally, we performed an odds ratio analysis to evaluate significant associations between COVID-19 symptoms and previous malaria infections. Results In 2020, 1547 malaria (97% were P. vivax) and 5968 COVID-19 cases were reported. Furthermore, 96 patients got COVID-19 after getting a malaria infection. From these, 87 were symptomatic (90.6%), and mostly adults, ages 30 to 59 (62.3%). Also, we found that malaria previous infections represent a risk for the presence of symptoms such as fever, cough, throat pain, and respiratory difficulty. Nevertheless, there was no significant association between these cases and hospitalization or death. Conclusion Our analysis suggests that previous malaria infections might affect COVID-19 symptomatology, which highlights the importance of a continuing control and surveillance malaria program to avoid potential syndemics with COVID-19.Introducción En los últimos años, el número de casos de malaria en las comunidades nativas de Condorcanqui, Amazonas ha aumentado considerablemente. La malaria por Plasmodium vivax es endémica en la región y en 2019 fue reportada la reintroducción de P. falciparum. Métodos En este estudio, recopilamos y analizamos los datos de malaria y COVID-19 reportados por la Dirección Regional de Salud (DIRESA) durante el 2020. Además, realizamos un análisis de razón de posibilidades “odds ratio” para evaluar las asociaciones significativas entre los síntomas de la COVID-19 y las infecciones previas de malaria. Resultados En el 2020, se reportaron 1547 casos de malaria (97% por P. vivax) y 5968 de COVID-19. Por otro lado, 96 pacientes contrajeron COVID-19 después de contraer una infección de malaria. De éstos, 87 eran sintomáticos (90,6%) y en su mayoría adultos de 30 a 59 años (62,3%). Además, encontramos que las infecciones previas de malaria están asociadas a la presencia de síntomas como fiebre, tos, dolor de garganta y dificultad respiratoria. Sin embargo, no hubo asociación significativa entre estos casos y la hospitalización o la muerte. Conclusión Nuestro análisis sugiere que las infecciones previas por malaria podrían afectar la sintomatología de la COVID-19, lo que destaca la importancia de un programa continuo de control y vigilancia de la malaria para evitar posibles sindemias con la COVID-19

Mesenchymal Stromal Cell-Based Therapies as Promising Treatments for Muscle Regeneration After Snakebite Envenoming

Snakebite envenoming is a global neglected disease with an incidence of up to 2.7 million new cases every year. Although antivenoms are so-far the most effective treatment to reverse the acute systemic effects induced by snakebite envenoming, they have a limited therapeutic potential, being unable to completely neutralize the local venom effects. Local damage, such as dermonecrosis and myonecrosis, can lead to permanent sequelae with physical, social, and psychological implications. The strong inflammatory process induced by snake venoms is associated with poor tissue regeneration, in particular the lack of or reduced skeletal muscle regeneration. Mesenchymal stromal cells (MSCs)-based therapies have shown both anti-inflammatory and pro-regenerative properties. We postulate that using allogeneic MSCs or their cell-free products can induce skeletal muscle regeneration in snakebite victims, improving all the three steps of the skeletal muscle regeneration process, mainly by anti-inflammatory activity, paracrine effects, neovascularization induction, and inhibition of tissue damage, instrumental for microenvironment remodeling and regeneration. Since snakebite envenoming occurs mainly in areas with poor healthcare, we enlist the principles and potential of MSCs-based therapies and discuss regulatory issues, good manufacturing practices, transportation, storage, and related-procedures that could allow the administration of these therapies, looking forward to a safe and cost-effective treatment for a so far unsolved and neglected health problem.The authors are supported by the University Pablo de Olavide (Sevilla), the University Miguel Hernández (Elche, Alicante), National University Toribio Rodriguez de Mendoza (Chachapoyas, Peru) Grants: Contrato N° 09-2019-FONDECYT-BM-INC.INV to JRT, JDRF 2-SRA-2019-837-S-B and AVI-GVA COVID-19-68 to BS, Fundación Andaluza de I+D and Al-Andalus Biopharma Project (FAID-2018-1). The authors CC-O, CG-D, and TCSA were supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil (CNPq) (Process: 406163/2018-9), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazil - CAPES (Program COFECUB Process: 88881.191812/2018-01) and by Fundação de Amparo à Pesquisa do Estado de Minas Gerais, Brazil (FAPEMIG).Ye

Outcomes in Newly Diagnosed Atrial Fibrillation and History of Acute Coronary Syndromes: Insights from GARFIELD-AF

BACKGROUND: Many patients with atrial fibrillation have concomitant coronary artery disease with or without acute coronary syndromes and are in need of additional antithrombotic therapy. There are few data on the long-term clinical outcome of atrial fibrillation patients with a history of acute coronary syndrome. This is a 2-year study of atrial fibrillation patients with or without a history of acute coronary syndromes