Biomedical subjects

Michael Xavier Doss

Publications and source records attributed to Michael Xavier Doss.

5 recordsLinked to original sources

PubMed2006

Generation and characterization of cardiomyocytes under serum-free conditions.

In vitro culturing of mammalian cells provides an elegant platform to study cell signaling, interactions, and metabolism as well as proliferation and differentiation processes. Often, these cells are cultured and maintained in sera obtained from animals such as horses, cows, and rabbits. The sera used for this purpose fluctuates in composition from individual animals and, hence, influences the cellular growth and differentiation at different magnitudes. This poses a need to use a substitute for sera in cell culture systems to overcome the observed variations. Here, we present and compare protocols for culturing of embryonic stem (ES) cells in serum-free conditions, derivation of germ layers, and cardiac differentiation of ES cells in both serum-free and serum-containing culture conditions. Differentiated embryoid bodies by serum-free protocols produce significantly increased frequencies of clusters of cardiac cells beating stronger than found in serum-containing media. Therefore, we conclude that the use of serum replacement media (SRM) in our experiments led to more specific differentiation but reduced proliferation because these SRMs contained reduced essential substances like growth factors and hormones. Unlike serum media, SRMs have a well-defined composition and are highly reproducible. Hence, SRM will be the ideal substitute for serum-containing media.

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PubMed2006

Dietary small molecules and large-scale gene expression studies: an experimental approach for understanding their beneficial effects on the development of malignant and non-malignant proliferative diseases.

Epidemiological studies have repeatedly demonstrated a correlation between nutrition, development and the severity of malignant and non-malignant proliferative diseases such as cancer and atherosclerosis. Therefore, the prevention of chronic proliferative diseases through dietary intervention is currently receiving considerable attention. Until now, much of the research is being focused on the cellular and molecular action mechanisms of dietary small molecules explaining their beneficial effects. Dietary chemicals may affect gene expression in several human diseases. However, significant progress has been made and several molecular action mechanisms have been proposed. Alteration of genetical pathways by nutrition, also called "Nutrigenomics", may offer a new approach for understanding the beneficial effects of dietary compounds on the development of severe polygenic diseases, such as cardiovascular disease, diabetes and hypertension. This review focuses on the nutritional genomics of dietary chemicals with a special emphasis on catechins. Catechins belong to the flavonoid family, which are polyphenolic compounds available in foods of plant origin. Several epidemiological studies have reported that consumption of flavonoids, and especially catechins might function as chemopreventive agents against cancer and cardiovascular diseases.

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PubMed2005

Trapping of growth factors by catechins: a possible therapeutical target for prevention of proliferative diseases.

The prevention of cancer through dietary intervention is currently receiving considerable attention. Several epidemiological studies substantiate that green tea has a protective effect against a variety of malignant proliferative disorders such as lung cancer, breast cancer and prostate cancer. This preventive potential of green tea against cancer is attributed to the biologically active flavonoids called catechins. Epigallocatechin 3-o-gallate, the major catechin found in green tea, mediates diverse physiological and pharmacological actions in bringing about the regression of the tumors and also lowers the risk of nonmalignant cardiovascular proliferative diseases. Much of the current research is being focused on how these catechins specifically bring about the regression of the experimentally induced tumors both in vitro and in vivo. These catechins exert diverse physiological effects against proliferative diseases by several mechanisms, most of which are not completely characterized. This review summarizes the mechanisms by which these catechins play an essential role in regulating the process of carcinogenesis, with a special emphasis on how these catechins antagonize the growth factor-induced proliferative disorders.

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PubMed2005

An optimized embryonic stem cell model for consistent gene expression and developmental studies: a fundamental study.

In vitro differentiation of embryonic stem (ES) cells results in generation of tissue-specific somatic cells and may represent a powerful tool for general understanding of cellular differentiation and development in vivo. Culturing of most ES cell lines requires murine embryonic fibroblasts (MEF), which may influence adventitiously the genetic differentiation program of ES cells. We compared the expression profile of key developmental genes in the MEF-independent CGR8 ES cell line and in the MEF-dependent D3 ES cell line. Using neomycin-resistant MEFs we demonstrated that MEFs are able to contaminate the D3 ES cells even after removing the MEFs. Subsequently, optimal differentiation conditions were established for the differentiation of CGR8 ES cells into various germ layer cells. Detailed gene expression studies in differentiating CGR8 cells were done by RT-PCR analysis and by microarray analysis demonstrating a general trend of the assessed genes to be expressed either in 3 days- or 10-days old embryoid bodies (EBs) when compared to undifferentiated ES cells. Subsets within the various functional gene classes were defined that are specifically up- or down-regulated in concert. Interestingly, the present results demonstrate that developmental processes toward germ layer formation are irreversible and mostly independent of the culture conditions. Notably, apoptotic and mitochondrial ribosomal genes were down- and up-regulated in 10-days old EBs, respectively, whereas compared to the 3-days old EBs whereas the activity of the extracellular signal-regulated kinase (ERK) 1/2 decreased with progressive development. This article defines a platform for ES cell differentiation and gene expression studies.

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PubMedDate not supplied

Embryonic stem cells: a promising tool for cell replacement therapy.

Embryonic stem (ES) cells are revolutionizing the field of developmental biology as a potential tool to understand the molecular mechanisms occurring during the process of differentiation from the embryonic stage to the adult phenotype. ES cells harvested from the inner cell mass (ICM) of the early embryo can proliferate indefinitely in vitro while retaining the ability to differentiate into all somatic cells. Emerging results from mice models with ES cells are promising and raising tremendous hope among the scientific community for the ES-cell based cell replacement therapy (CRT) of various severe diseases. ES cells could potentially revolutionize medicine by providing an unlimited renewable source of cells capable of replacing or repairing tissues that have been damaged in almost all degenerative diseases such as diabetes, myocardial infarction and Parkinson's disease. This review updates the progress of ES cell research in CRT, discusses about the problems encountered in the practical utility of ES cells in CRT and evaluates how far this approach is successful experimentally.

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