Tissue-based, High Throughput
Screening (HTS) Update96-Well EpiDerm™ Version Now Available
MatTek is pursuing a Tissue-based, High Throughput Screening (HTS) solution involving the use of several of our normal human cell, three dimensional organotypic in vitro tissue models. This process began several years ago when MatTek first received funding via the NIH SBIR program for a Phase I and then a Phase II High Throughput Screening (HTS) research program.
24-well plate configuration
The HTS tissue models derived from this program will find application in product safety assessment and gene regulation studies for a broad variety of pharmaceutical, chemical, and consumer product companies who need to screen a large number of candidate materials. The models will also be adaptable for other basic research involving modulation of gene messages in skin and airway epithelia.
The feasibility of producing high throughput screening (HTS) epidermal tissue models and testing methodologies was demonstrated in the completed Phase I studies. Epidermal tissues (EpiDerm™) were produced in both 24- and 96-well plate formats. Protocols and reagents for HTS assessment of tissue viability and isolation of RNA from these tissues were also developed. Various quantitative assays for monitoring gene specific mRNA levels were analyzed. Of the methods tested, quantitative real-time polymerase chain reaction (PCR) was found to be the most applicable for HTS testing.
Phase II research, underway for almost 1 year, will further develop the results of Phase I. Phase I testing protocols will be optimized and the HTS technology will be expanded to a three-dimensional organotypic tracheal bronchial tissue model (EpiAirway™).
96-well plate configuration
Phase II goals include providing in vitro models of human epithelial tissues in 96-well and 24-well high-throughput screening (HTS) formats and developing associated methodologies to enable researchers in the pharmaceutical, chemical and personal care industries to utilize these tissues to rapidly screen chemicals, ingredients and finished products for effects on modulation of gene expression for any gene of interest. Attainment of these goals will provide important tools for eliminating bottlenecks in safety and efficacy screening, as well as aid discovery processes in modern industrial product development.
The HTS models being developed in Phase II are derived from normal human cells cultured at the air/liquid interface to produce three-dimensional organotypic tissues. The epidermal model used during Phase I will display a stratified differentiated structure, including a stratum corneum possessing barrier function similar to native epidermis.
In addition, Phase II studies have been expanded upon Phase I results to include HTS tracheal/bronchial epithelial (EpiAirway™) tissue (a 24-well version is now available). This tissue is pseudo-stratified, displays a differentiated mucociliary phenotype and barrier properties similar to native tracheal/bronchial epithelium, including development of transepithelial electrical resistance (TEER), conferred by functional tight junctions.
The utility of the HTS EpiDerm tissue models and RNA isolation products will be demonstrated by quantitative real-time PCR analysis of gene expression for angiogenesis genes. In addition, the HTS tracheal bronchial model (EpiAirway) will be used to investigate the cytokine induced regulation of genes involved in airway inflammation and respiratory diseases.
Please contact MatTek to discuss your in vitro airway or skin tissue model High Throughput Screening (HTS) needs.
|
