The AlfaGene Advantage

AlfaGene BioScience's possesses proprietary technology and systems, not only, for the procurement, isolation, and long term culturing of human adult gastrointestinal (GI) stem cells, but also, the ability to direct these stem cells to differentiate into the epithelial cell types normally found lining the GI tract in vivo, and the ability to establish and maintain these non-transformed human intestinal primary epithelial cell (HIPEC) lines derived from these stem cell lines in culture for many passages over a long period of time.

     Significant progress has been made in studies of the functional capabilities of stem and intestinal epithelial cells (IEC), and of the ways in which they may be altered in acute and chronic inflammatory or malignant states, by using 1) malignant transformed cell lines, 2) isolated epithelial cells, and 3) animal models. In all cases, however, inaccuracies have arisen in extrapolating from the data obtained utilizing these methods, since each method has inherent limitations and differs markedly from the in vivo state of the stem and epithelial cells being examined (see table below).  For example, transformed malignant cell lines, by their very nature, differ significantly in their behavior, as compared to primary cell lines or in vivo.  Transformed cell lines usually have chromosomal abnormalities that cause instability, as well as, abnormal growth growth characteristics and altered gene expression patterns. Tumor cell lines also suffer variability issues from cell line to cell line, and from passage to passage.  The use of freshly isolated epithelial or stem cells is often complicated, not only by the concurrent isolation and contamination with a mixture of several additional cell types including T cells, B cells, or macrophages (especially when inflamed tissue is used as cell source) and low yields, but also, by the fact that the isolation procedure itself can alter the phenotype of the cells by cleaving certain molecules from the cell surface.  Furthermore, surface and crypt epithelial cells may have different phenotypes and functions and are not usually fully represented in separated populations.  Also, entities, other than AlphaGene, have been unable to culture and expand these stem and primary cell populations.  In an attempt to resolve some of these problems, transformed epithelial cell lines have been established from human, mouse and rat epithelium.  Although this model system allows the cells to retain some specific functions and indefinite survival, there has been concern about the altered growth control and gene expression patterns in these cells through the transfection of viral DNA (such as the large T - antigen gene from SV40). Similarly, findings with animal model systems show that these models do not always precisely mimic the functional scenarios of human intestinal epithelial cells in vivo.   

     AlfaGene’s technology enables the generation and long-term maintenance in culture of stem and nontransformed primary cell lines derived from tissue samples, thus avoiding the issues associated with changes induced by transformation, limited yields, species differences, limited life-span, and non-uniformity.  Development of primary epithelial cell and stem lines has long been considered as one of the needed resources and focuses to advance the research priorities of several national and international organizations.

         Current methodologies, their shortcomings, and the advantage of AlfaGene’s system

There are many advantages of using AlfaGene's novel platform for basic biological research as well as for discovery and development of disease markers and new therapeutics. Availability of continuous pure population of diseased and normal tissue derived primary epithelial cells in sufficient quantity provides an opportunity for identification of cellular, molecular, and genetic species involved in the disease development process. This provides our company with a significant differentiation and advantage from any other existing company in the field.