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Terapia celular y regeneración cardiaca. ¿Dónde estamos?

2012 , Lara-Martínez, Luis Andrés , Navarro Betancourt, Refugio , Hernández Gutiérrez, Salomón

La terapia celular es un recurso prometedor para el tratamiento de la cardiopatía isquémica; mediante un procedimiento como la infusión directa o intravascular de células troncales al tejido dañado, es posible restituir la capacidad funcional del corazón. A pesar del éxito de los ensayos en animales, en humanos no se han obtenido los resultados esperados; además, se presenta una serie de limitantes éticas y prácticas que ponen en duda los resultados. Se ha comprobado que la terapia con células troncales mejora las propiedades electromecánicas del tejido cardiaco como tal; sin embargo, el beneficio funcional aún es poco convincente, pero no desalentador. La realización de ensayos clínicos más grandes y el perfeccionamiento de técnicas de seguimiento no invasivas son necesarios para evaluar de manera integral el beneficio de la terapia celular. Por otra parte, el problema de la supervivencia de las células injertadas es un conflicto relevante, lo que hace que la eficiencia de las células a transferir sea variable y generalmente baja; esto es causado principalmente por tres procesos: apoptosis, isquemia e inflamación. Hasta ahora, el mecanismo más prometedor para incrementar la viabilidad del injerto es la sobreexpresión de proteínas antiapoptóticas. Sin duda, el principal desafío para la terapia celular será determinar la estirpe más adecuada para el tratamiento. En esta revisión se describen los principales tipos de células que a la fecha han sido propuestas para la regeneración cardiaca: las células troncales embrionarias, las células pluripotentes inducidas, las células derivadas de médula ósea, los mioblastos esqueléticos y las células de tejido adiposo, entre otras.

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Células madre: buscando marcadores de superficie celular que predispongan compromiso de diferenciación cardiaca

2018 , Lara Martínez, Luis Andrés , Gutiérrez Villegas, Ingrid , Arenas Luna, Victor Manuel , Hernández Gutiérrez, Salomón

Actualmente las enfermedades cardiovasculares se han convertido en un serio problema para los sistemas de salud de todo el mundo, ya que son la principal causa de muerte y representan una enorme carga económica. Este problema ha sido abordado con diferentes estrategias, entre ellas con la ayuda de terapia celular, aunque sin resultados contundentes. Durante más de 20 años, se ha utilizado una gran variedad de células madre en diferentes modelos de infarto del miocardio. El uso de células madre cardiacas (CSC) parece ser la mejor opción, pero la inaccesibilidad y la escasez de estas células hacen que su uso sea muy limitado. Además, existe un riesgo elevado pues tienen que obtenerse directamente del corazón del paciente. A diferencia de las CSC, las células madre adultas derivadas de médula ósea o tejido adiposo, entre otras, representan una opción atractiva debido a su fácil accesibilidad y abundancia, pero sobre todo a la probable existencia de progenitores cardiacos entre sus diferentes subpoblaciones. En esta revisión hacemos un análisis de los marcadores de superficie presentes en CSC en comparación con otras células madre adultas, y sugerimos la preexistencia de células que comparten marcadores de superficie específicos con CSC, la presencia de un inmunofenotipo predecible, aunque en proporciones bajas, pero con un potencial de diferenciación cardiaca similar a las CSC, lo cual podría aumentar su valor terapéutico. Este estudio revela las nuevas perspectivas con respecto a la presencia de dichos marcadores, los cuales comprometerían algunas de estas subpoblaciones a diferenciarse a tejido cardiaco.

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Antiproliferative activity of standardized phytopreparations from Ibervillea sonorae (S. Watson) Greene

2021 , Vidal-Gutiérrez, Max , Torres-Moreno, Heriberto , Hernández Gutiérrez, Salomón , Velázquez, Carlos , Robles-Zepeda, Ramón E. , Vilegas, Wagner

Ibervillea sonorae (Cucurbitaceae) is a medicinal plant utilized in Northwest Mexico against Diabetes and cancer. This natural product is taken orally, its presentation is capsules containing the plant’s dried and powdered caudices. There is no regulation or standardized dosage that allows reproducibility of its pharmacological effects. Cucurbitacins are the main group of compounds found in I. sonorae and are known for their antiproliferative activity in cancer cells. Cucurbitacin IIb (CIIb), one of the compounds present in I. sonorae, has demonstrated in experimental models with HeLa cervical cancer cells an apoptotic and anti-tumoral activity. The objective of this study is to obtain and standardize two phytopreparations of I. sonorae based on their CIIb content, evaluate their antiproliferative activity in cancer cell lines, and compare the results with those obtained with CIIb; expecting to find phytopreparations with anti-cancer potential. APCI-IT-MSn is utilized for the identification of cucurbitacins, FT-ICR-MS/MS for the quantification of CIIb, and the MTT assay for the evaluation of the antiproliferative activity. The CIIb content was 0.67% for Fito-Ison-EtOH and 1.84% for Fito-Ison-EtOAc. In both phytopreparations, six cucurbitacins have been identified, and a seventh one not previously identified. Phytopreparations were more effective against HeLa, with IC50 of 30.0 and 18.6 µg/mL for Fito-Ison-EtOH and Fito-Ison-EtOAc, respectively. This effect is lower than observed on CIIb in HeLa (5.8 µg/mL). There are no significant differences (p > 0.05) in the antiproliferative activity between Fito-Ison-EtOAc and CIIb in A549, LS180, and MDA-MB-231 cells. Phytopreparations of I. sonorae have potential for the development of anti-cancer products.

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NF-κB signaling blockade by Bay 11-7085 during early cardiac morphogenesis induces alterations of the outflow tract in chicken heart

2006 , Hernández Gutiérrez, Salomón , García-Peláez, I. , Zentella-Dehesa, Alejandro , Ramos Kuri, Manuel , Rojas, Emilio , Hernández-Franco, Pablo , Hernández-Sánchez, Fernando

Nuclear factor κB (NF-κB) is a pleiotropic transcription factor implicated in the regulation of diverse morphologic cardiac alterations, for which the p50 and p65 subunits form the most prevalent dimeric form in the heart. NF-κB is inactivated by proteins of the IκB family, which trap it in the cytoplasm. It is not known whether NF-κB influences cardiac development. Objective: Here we investigated the role of NF-κB in regulating transcription in chicken heart morphogenesis. Specifically, we tested whether NF-κB activation is required for normal formation of the outflow tract (OFT) during a critical stage of heart development. Methods and results: We designed a reporter vector with κB binding sites for Rel family members in the promoter, upstream from the cDNA of Green Fluorescent Protein (GFP). This construct was injected directly into the developing heart of chicken embryos. NF-κB activation was subsequently inhibited by administration of the specific pharmacological agent Bay 11-7085. We found that forced NF-κB expression was associated with multiple congenital cardiac alterations of the OFT (mainly IVC, DORV and great arteries stenosis). Conclusion: These findings indicate that blockade of NF-κB induces apoptosis and is an important factor in the development of OFT during cardiogenesis. However, it remains unknown which members of the Rel family are relevant in this process. ©Apoptosis

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STR data for 15 loci in a population sample from the central region of Mexico

2005 , Hernández Gutiérrez, Salomón , Hernández-Franco, Pablo , Martínez-Tripp, Sara C. , Ramos Kuri, Manuel , Rangel-Villalobos, Héctor

A Mexican population sample was obtained from the central region of the country, including five states. Two hundred and eleven individuals were PCR-typed for 15 STR loci with the AmpFι STR Identifiler PCR amplification kit (Applied Biosystems). The following autosomal markers were analyzed: D8S1179, D21S11, D7S820, CSF1PO, D19S433, vWA, TPOX, D18S51, D3S1358, TH01, D13S317, D16S539, D2S1338, D5S818, FGA and Amelogenin. Allele frequencies for each STR were estimated and compared to previous reports. Genotype distribution by locus and by two loci combination was in agreement with Hardy–Weinberg expectations for all 15 STRs. This STR system in Mexican-mestizos presented a combined probability of exclusion (PE) and discrimination (PD) longer than 99.999%.

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Adipose tissue-derived stem cells expressing cardiac progenitor markers: The best source of mesenchymal stem cells for cardiovascular repair?

2014 , Navarro Betancourt, Refugio , Baldassarri Ortego, Bruno , Urquiza y Conde, F. , Hernández Gutiérrez, Salomón

At the present time a wide variety of stem cell lineages have been explored for the treatment of ischemic cardiomyopathy; currently, the reference cells for cardiac cell therapy are cardiac stem cells (CSCs), because these cells have a specific differentiation commitment into cardiac tissues [ 1 , 2 , 3 ]. In comparison with other cell types, this intrinsic commitment is inversely related to the capacity to differentiate into diverse tissues (Fig. 1). Despite this efficient differentiation, a specific immunophenotype for CSC identification is yet to be meticulously defined. In addition, the use of CSC in a clinical setting is severely hindered by their availability. These obstacles to the use of CSC for cardiac cell therapy have prompted the search for readily more attainable stem cell sources, even if they have a broader differentiation spectrum, such as mesenchymal stem cells (MSCs).

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Data on sodium tetraborate as a modulation of hypertrophic intracellular signals

2021 , Roque-Jorge, J. , Hernández Gutiérrez, Salomón , Díaz-Rosas, Guadalupe , García-Chéquer, Adda Jeanette , Lopez-Torres, Adolfo , Contreras-Ramos, Alejandra

The present work benefits the use of sodium tetraborate to prevent and treat hypertrophic cardiac. The data obtained from the work could serve as a reference point to compare with data obtained in vivo studies with cardiac damage. This research will be an advantage for future researches to stimulate the ones focused on developing food supplements to prevent heart diseases such as cardiac hypertrophic. This article also indicates the data on the optimal concentration of isoproterenol as an inducer of hypertrophy in cardiomyocytes. Also, data of the cytotoxic effect of sodium tetraborate on normal cardiomyocytes is revealed. Finally, data of viability, cell size, proliferation nuclear antigen (PCNA) and apoptosis is shown. The expression of transcription factors linked to hypertrophy such as GATA-4, MEF2c, NFAT, CDk9, and myogenin was also quantified by immunofluorescence. The mRNA expression of adrenergic receptors (alpha and beta), AKT1 and Erk1 / 2 and genes of early response to hypertrophy (c-myc, c-fos, c-jun) are also shown as Cts of RT-qPCR. GAPDH and 18 s were used as housekeeping genes.

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Effect of Functionalized Carbon Nanotubes and their Citric Acid Polymerization on Mesenchymal Stem Cells In Vitro

2018 , Garnica Gutiérrez, Rosa , Lara Martínez, Luis Andrés , Palacios, Eduardo , Massó, Felipe A. , Contreras, Alejandra , Hernández Gutiérrez, Salomón , Cervantes-Sodi, Felipe

The effects of acid-functionalized and polycitric acid- (PCA-) polymerized carbon nanotubes (CNTs) in contact with the extracellular membrane of mesenchymal stem cells (MSC), a genetically unmodified cell line with differentiation capability, was evaluated with different cellular parameters. The modified CNTs show differences in the analyzed biological behaviors, that is, intracellular incorporation, cell proliferation, apoptosis, and cytotoxicity as compared with those unpolymerized nanotubes. Due to the reduced cellular uptake of polymerized CNTs, PCA-polymerized CNTs are less cytotoxic and are associated with less apoptotic cell death than the acid-functionalized ones. The effects of nitrogen-doped CNTs (CNx) is also reported, showing that functionalized undoped CNTs present strong stimulation of cell proliferation, whereas functionalized and polymerized CNxs stimulate an apoptotic behavior. The study of MSCs in contact with CNTs and PCA is challenging due to the complexity of its various signaling components. Our results provide basis for further studies aimed to understand the relevant role that the interaction of these nanotubes with extracellular membrane could have a crucial structure for tissue grafting. © 2018 Hindawi Limited, Rosa L. Garnica-Gutiérrez et al.

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In Vitro Evidence of Differential Immunoregulatory Response between MDA-MB-231 and BT-474 Breast Cancer Cells Induced by Bone Marrow-Derived Mesenchymal Stromal Cells Conditioned Medium

2022 , Arenas Luna, Victor Manuel , Montesinos, Juan José , Cortés-Morales, Víctor A. , Cisneros, Bulmaro , Navarro Betancourt, Refugio , Peralta-Ildefonso, Martha Janneth , Hernández Gutiérrez, Salomón

Inside tumors, cancer cells display several mechanisms to create an immunosuppressive environment. On the other hand, by migration processes, mesenchymal stromal cells (MSCs) can be recruited by different cancer tumor types from tissues as distant as bone marrow and contribute to tumor pathogenesis. However, the impact of the immunoregulatory role of MSCs associated with the aggressiveness of breast cancer cells by soluble molecules has not been fully elucidated. Therefore, this in vitro work aimed to study the effect of the conditioned medium of human bone marrow-derived-MSCs (hBM-MSC-cm) on the immunoregulatory capability of MDA-MB-231 and BT-474 breast cancer cells. The hBM-MSC-cm on MDA-MB-231 cells induced the overexpression of TGF-β, IDO, and IL-10 genes. Additionally, immunoregulation assays of mononuclear cells (MNCs) in co-culture with MDA-MB-231 and hBM-MSC-cm decreased lymphocyte proliferation, and increased proteins IL-10, TGF-β, and IDO while also reducing TNF levels, shooting the proportion of regulatory T cells. Conversely, the hBM-MSC-cm did not affect the immunomodulatory capacity of BT-474 cells. Thus, a differential immunoregulatory effect was observed between both representative breast cancer cell lines from different origins. Thus, understanding the immune response in a broader tumor context could help to design therapeutic strategies based on the aggressive behavior of tumor cells.

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On the existence of cardiomesenchymal stem cells

2015 , Navarro Betancourt, Refugio , Hernández Gutiérrez, Salomón

The most efficient cells for cardiac regeneration are myocardium-resident cardiac stem cells. However, the limited availability of these cells restricts their utility for cardiac cellular therapy. Mesenchymal stem cells can differentiate into a wide variety of tissues, but it is not simple to accurately direct cell differentiation into a specific lineage, such as cardiac tissue; this renders a low efficiency for cardiac regeneration therapy. Given the heterogeneity of mesenchymal stem cells, it may be possible to find specific stem cell subpopulations with a definite differentiation capacity toward cardiac lineage. A parameter to assess cardiac differentiation specificity could be surface marker expression; a population with an immunophenotype similar to cardiac stem cells may have a superior therapeutic value than unsorted mesenchymal stem cells. We hypothesize the existence of a cell line that combines the expression of cardiac stem cell surface markers with those of mesenchymal stem cells, a suitable name for this population is cardiomesenchymal stem cells (CMSC); such cells would be ideal for cardiac regeneration.