Propagenix has two distinct technologies for the massive expansion of normal or diseased primary epithelial cells, Conditional Reprogramming (CR) technology and EpiX™ technology. Both technologies share particular attributes: epithelial progenitor cells become highly proliferative in these growth-promoting conditions, no transfection or transduction of genetic material is involved, genomic integrity is preserved, and propagated epithelial cells readily return to their committed differentiation fate upon removal from CR and EpiX™ media. While both technologies have a generic, platform utility for cell expansion, they do differ in their ability to support growth of certain cell types.
Conditional Reprogramming (CR) technology is a revolutionary new approach to generating unprecedented quantities of biologically important cell types ex vivo that retain the ability to re-adopt the relevant functionality of the tissues from which the cells originated. It offers significant and enabling advantages compared with currently available methods.
Animal models have been employed in biomedical research for decades as a surrogate system that allows scientists to explore basic and translational research questions prior to, or in lieu of, the use of human subjects. As cell culture technology has evolved, commercially available primary cells and continuous cell lines have become widely used for some studies to avoid the expense, long time frames and ethical concerns associated with animal studies. Recent advances in induced pluripotent stem cell (iPSC) technologies have raised hopes that they can provide a source of cells to create personalized disease models, to screen for precision therapeutics, and even to provide biomaterial for cell and tissue replacement therapies.
When mature epithelial cells are introduced into CR culture conditions, they adopt a tissue-specific progenitor phenotype and become proliferative. Primary epithelial cells from airway tissues, retina, prostate, breast, intestine, pancreas, liver biliary duct and other tissues have all proven to be induced to replicate for extended periods under CR conditions. On removal from the CR culture conditions, these cells re-adopt their original differentiation state, hence the conditional nature of the process. No genetic modification is involved in the switch between the replicative and differentiated phenotypes, and no complex re-differentiation strategy is required for the cells to return to their normal functional phenotype. The technology has also been employed successfully to propagate cells from primary tumors, metastatic tumors and patient-derived xenografts.
While CR technology offers a powerful method for the massive expansion of primary epithelial cells, there are applications that require a culture system devoid of feeder cells and/or serum. Propagenix has developed a non-derivative and novel serum-free and feeder-free culture medium (EpiX™ medium) that allows for greater than 1012-fold expansion of several types of primary epithelial cells without using viral or oncogenic factors. EpiX™-expanded primary epithelial cells maintain normal chromosome karyotype after more than 40 population doublings (i.e., over a trillion-fold expansion). In addition, EpiX™-expanded primary epithelial cells can differentiate into tissue structures resembling their original epithelial origin upon exiting the proliferation conditions. Second-generation versions of EpiX™ medium lacking animal-derived components now provide Propagenix unique manufacturing- and regulatory-friendly solutions, enabling generation of sufficient biomass needed for cell replacement therapy for various diseases affecting epithelial tissues.