Desarrollo de un implante de CMM modificadas genéticamente para reemplazo de cartílago

Debido a la escasa capacidad de regeneración del cartílago articular, numerosos estudios han explorado nuevas terapias basadas en células para el tratamiento de lesiones condrales. Tras la estimulación con factores de crecimiento, las células madre mesenquimales (CMMs) derivadas de tejido adiposo tienen la capacidad de diferenciarse en tejidos conectivos tales como cartílago, hueso, etc. A pesar de que las CMMs son potencialmente útiles como fuente de células alternas a los condrocitos, se requieren mejores métodos para estimular efectivamente suproliferación y diferenciación a condrocitos. En este estudio, se evaluó la condrogénesis in vitro de las CMMs derivadas de tejido adiposo, después de modificarlas genéticamente con vectores adenovirales que codifican para factores de crecimiento condrogénicos. MÉTODOS. Se construyeron vectores adenovirales que portan el cDNA codificante para TGF

Células madre

Las células madre tienen la capacidad de autorenovarse y diferenciarse para producir diversos tipos de células especializadas. Las células madre se clasifican por su potencial de diferenciación en totipotenciales, pluripotenciales y multipotenciales, y según el tejido de origen en embrionarias o adultas. Estas células generan gran interés por los diferentes modelos de diferenciación a los que pueden conducirse: desde el modelo convencional (célula madre-célula hija), hasta procesos de transdiferenciación y desdiferenciación celular. Estos modelos se aplican para entender el fenómeno de plasticidad. Se denomina plasticidad de las células madre a la capacidad de generar diferentes grupos celulares a los de su tejido de origen, como las de las células madre hematopoyéticas, que forman hepatocitos y miocitos en condiciones controladas. En la actualidad existen controversias éticas, ya que los estudios en células madre se realizan a partir de óvulos donados en los centros de fertilización humana; sin embargo, pueden obtenerse células madre con características pluripotenciales de otras fuentes, como las del líquido amniótico. La legislación internacional, respecto de la obtención de células madre es heterogénea y divergente, mientras que la legislación nacional resulta limitada ante los retos que plantea la investigación científica

Comparative Pathogenicity of Lomentospora prolificans (Scedosporium prolificans) Isolates from Mexican Patients

We identified 11 Lomentospora prolificans isolates recovered from Mexican patients using phenotypic and molecular characteristics. The identification of isolates was assessed by internal transcribed spacer (ITS rDNA) sequencing. In vitro susceptibility to amphotericin B, fluconazole, voriconazole, posaconazole, caspofungin, anidulafungin and micafungin was determined according to Clinical and Laboratory Standards Institute (CLSI) procedures. Three isolates (07-2239, 11-2242 and 04-2673) were used to induce systemic infection in immunocompetent ICR mice. Survival and tissue burden studies were used as markers of pathogenicity. All of the strains were resistant to every antifungal tested with MIC’s for AmB (8–[8 lg/ml), VRC (16–[16 lg/ml), PSC (16– [16 lg/ml), FLC (64–[64 lg/ml) and echinocandins with MICs C8 lg/ml. One hundred, ninety and sixty percent of the infected mice with the strains 07-2239, 11-2242 and 04-2673 died during the study, respectively. Regarding tissue burden, the highest fungal load of the infected mice was detected in brain followed by spleen and kidney, regardless of the strain

Evaluation of in vivo pathogenicity of Candida parapsilosis, Candida orthopsilosis, and Candida metapsilosis with different enzymatic profiles in a murine model of disseminated candidiasis

Six isolates of the Candida parapsilosis complex with different enzymatic profiles were used to induce systemic infection in immunocompetent BALB/c mice. Fungal tissue burden was determined on days 2, 5, 10, and 15 post challenge. The highest fungal load irrespective of post-infection day was detected in the kidney, followed by the spleen, lung,andliver,withatendencyforthefungalburdentodecreasebyday15inallgroups. Significant differences among the strains were not detected, suggesting that the three species of the “psilosis” group possess a similar pathogenic potential in disseminated candidiasis regardless of their enzymatic profile

Evaluation of in vivo pathogenicity of Candida parapsilosis, Candida orthopsilosis, and Candida metapsilosis with different enzymatic profiles in a murine model of disseminated candidiasis

Six isolates of the Candida parapsilosis complex with different enzymatic profiles were used to induce systemic infection in immunocompetent BALB/c mice. Fungal tissue burden was determined on days 2, 5, 10, and 15 post challenge. The highest fungal load irrespective of post-infection day was detected in the kidney, followed by the spleen, lung,andliver,withatendencyforthefungalburdentodecreasebyday15inallgroups. Significant differences among the strains were not detected, suggesting that the three species of the “psilosis” group possess a similar pathogenic potential in disseminated candidiasis regardless of their enzymatic profile

Analyses of chondrogenic induction of adipose mesenchymal stem cells by combined co-stimulation mediated by adenoviral gene transfer

INTRODUCTION: Adipose-derived stem cells (ASCs) have the potential to differentiate into cartilage under stimulation with some reported growth and transcriptional factors, which may constitute an alternative for cartilage replacement approaches. In this study, we analyzed the in vitro chondrogenesis of ASCs transduced with adenoviral vectors encoding insulin-like growth factor-1 (IGF-1), transforming growth factor beta-1 (TGF-β1), fibroblast growth factor-2 (FGF-2), and sex-determining region Y-box 9 (SOX9) either alone or in combinations. METHODS: Aggregate cultures of characterized ovine ASCs were transduced with 100 multiplicity of infections of Ad.IGF-1, Ad.TGF-β1, Ad.FGF-2, and Ad.SOX9 alone or in combination. These were harvested at various time points for detection of cartilage-specific genes expression by quantitative real-time PCR or after 14 and 28 days for histologic and biochemical analyses detecting proteoglycans, collagens (II, I and X), and total sulfated glycosaminoglycan and collagen content, respectively. RESULTS: Expression analyses showed that co-expression of IGF-1 and FGF-2 resulted in higher significant expression levels of aggrecan, biglycan, cartilage matrix, proteoglycan, and collagen II (all P ≤0.001 at 28 days). Aggregates co-transduced with Ad.IGF-1/Ad.FGF-2 showed a selective expression of proteoglycans and collagen II, with limited expression of collagens I and × demonstrated by histological analyses, and had significantly greater glycosaminoglycan and collagen production than the positive control (P ≤0.001). Western blot analyses for this combination also demonstrated increased expression of collagen II, while expression of collagens I and × was undetectable and limited, respectively. CONCLUSION: Combined overexpression of IGF-1/FGF-2 within ASCs enhances their chondrogenic differentiation inducing the expression of chondrogenic markers, suggesting that this combination is more beneficial than the other factors tested for the development of cell-based therapies for cartilage repair

Multivariate feature selection of image descriptors data for breast cancer with computer-assisted diagnosis

Breast cancer is an important global health problem, and the most common type of cancer among women. Late diagnosis significantly decreases the survival rate of the patient; however, using mammography for early detection has been demonstrated to be a very important tool increasing the survival rate. The purpose of this paper is to obtain a multivariate model to classify benign and malignant tumor lesions using a computer-assisted diagnosis with a genetic algorithm in training and test datasets from mammography image features. A multivariate search was conducted to obtain predictive models with different approaches, in order to compare and validate results. The multivariate models were constructed using: Random Forest, Nearest centroid, and K-Nearest Neighbor (K-NN) strategies as cost function in a genetic algorithm applied to the features in the BCDR public databases. Results suggest that the two texture descriptor features obtained in the multivariate model have a similar or better prediction capability to classify the data outcome compared with the multivariate model composed of all the features, according to their fitness value. This model can help to reduce the workload of radiologists and present a second opinion in the classification of tumor lesions

Multivariate feature selection of image descriptors data for breast cancer with computer-assisted diagnosis

Breast cancer is an important global health problem, and the most common type of cancer among women. Late diagnosis significantly decreases the survival rate of the patient; however, using mammography for early detection has been demonstrated to be a very important tool increasing the survival rate. The purpose of this paper is to obtain a multivariate model to classify benign and malignant tumor lesions using a computer-assisted diagnosis with a genetic algorithm in training and test datasets from mammography image features. A multivariate search was conducted to obtain predictive models with different approaches, in order to compare and validate results. The multivariate models were constructed using: Random Forest, Nearest centroid, and K-Nearest Neighbor (K-NN) strategies as cost function in a genetic algorithm applied to the features in the BCDR public databases. Results suggest that the two texture descriptor features obtained in the multivariate model have a similar or better prediction capability to classify the data outcome compared with the multivariate model composed of all the features, according to their fitness value. This model can help to reduce the workload of radiologists and present a second opinion in the classification of tumor lesions

E-Cadherin gene expression in oral cancer : clinical and prospective data

Low protein expression of E-cadherin in oral squamous cell carcinoma (OSCC) has been associated with clinical and histopathological traits such as metastases, recurrence, low survival and poor tumor differentiation, and it is considered a high-risk marker of malignancy. However, it is still unknown whether low expression of E-cadherin is also present at the mRNA level in OSCC cases. Objective: The aim of this study was to compare E-cadherin mRNA expression in OSCC patients and controls and to correlate the expression with clinical and prospective characteristics. Forty patients and 40 controls were enrolled. E-cadherin mRNA expression was evaluated by quantitative real-time polymerase chain reaction using TaqMan probes. E-cadherin mRNA expression was significantly decreased in OSCC patients compared to that of controls (p<0.001). Whereas no significant association between clinical parameters and E-cadherin expression levels was observed, we noted lower E-cadherin expression levels in patients with positive lymph node metastasis. E-cadherin mRNA expression was markedly diminished in OSCC, in agreement with previous results that examined E-cadherin expression at the protein level. E-cadherin is downregulated in the early clinical stages of OSCC, and its mRNA levels do not change significantly in the advanced stages, suggesting that there is limited usefulness of this parameter for predicting disease progression