In vivo molecular pathology and pharmacology
What is the advantage of studying cells in their in vivo (patho)physiological environment and why does this give more information about your (new) drug than performing in vitro research?
50% of attrition in the clinical phase of drug development is attributed to lack of efficacy and unwanted toxicity of the new drug. It is safe to conclude, that
- we are not fully aware on the true molecular basis of human disease.
- we lack knowledge on how a new drug in the drug development pipeline affects cells in complex in vivo tissues
Eliminating these two important issues will allow you to make better drugs faster. We can assist you in creating a superior strategy for this purpose.
Cell behaviour in health and disease is intricately linked to a the microenvironment of cells. Studying in vivo cell dysfunction and responses to drugs is what matters, but the interpretation of whole tissue analysis is often hampered by the complexity of the tissue.
The Vivomicx approach assigns drug effects and cell behaviour in complex tissue to certain cell types. This compartmentalization will provide a better insight in the true pharmacological behaviour of your new compound in relation to the disease status.
The Vivomicx Approach
Isolation of cells from tissue sections We developed a well validated protocol for analysing gene expression profiles in subsets of cells in complex tissues from animal and human origin.
Using laser dissection microscopy, we isolate predestined cells from tissue sections and subject their RNA to quantitative RT-PCR analysis. It provides a unique way to unmask the molecular control of cell behaviour in different compartments of healthy and diseased tissues. Also, the effects of therapeutic intervention can be analysed at the molecular level in the cells you are interested in.
Our technology allows the analysis of small groups of cells with comparable features that, (patho)physiologically and genetically, are best compared to single cells. The analysis of single cells and small groups of similar cells was until recently hampered by the low amount of material available for subsequent read-out technologies. Thus, routine work on such samples was not possible.
Only recently this has changed due to technological breakthroughs, including application of lasermicrodissection that now routinely ensures good quality RNA for real-time (RT)PCR (see e.g., Yee et al., BMC Res Notes. 2014), and also allows protein based read-out techniques to be applied (recently reviewed by us, Langenkamp et al, Cell Tissue Res 2013). Nature Selected in 2013 "Single-Cell Sequencing" as the method of the year.
According to Nature, the methods to determine DNA and RNA content and identity of single cells "are poised to transform many areas of biology and medicine", generating important new insights in many areas in biology and biomedicine.