In a major effort to economize drug discovery in terms of cost and time, Manipal Institute of Regenerative Medicine (MIRM) & Stempeutics Research Pvt. Ltd. will now offer pharmaceutical companies engaged in drug discovery research a platform for drug screening and toxicity using human embryonic stem cells.

The researchers assert that the data extrapolated using embryoid bodied (EB)derived from human embryonic stem cells for drug screening and drug toxicity studies is far more reliable and authentic than animal studies. It will help pharmaceutical companies to economize time and cost.

In a research finding, MIRM and Stempeutics have discovered that the presence of small amount of lipopolysaccahrides (LPS) can cause birth defects and poor development of bones in a growing fetus. Pre-clinical studies of drug molecule are performed either on transformed cell lines or mice. Many a time the data cannot be extrapolated for human trials. Companies fail with the drug during the clinical trials and it is also difficult to identify side effects of the drug in pregnant women.

"The EB is mimicking the process of fetal development in a Petri dish where all the lineages such as ectoderm, mesoderm and endoderm are available. We have been able to show that small amount of toxins can lead to mesoderm abnormality which results in defective bone, formation," Dr Satish Totey, chief scientific officer, Stempeutics Research and director, MIRM told Pharmabiz.

Both MIRM and Stempeutics are getting ready to offer a platform to pharmaceutical companies who could now test drug molecules using the EB which can easily provide data on the possible birth defects and other side effects if taken by pregnant women. Earlier such studies were performed on mice, informed Dr Totey.
LPS is an endotoxin and the main antigenic component of gram negative bacterial cell wall causing vaginosis. It is regularly shed in the surrounding environment where the embryos grow.

The study was led by Dr Kaushik Deb, group leader and Principal Scientist, Embryonic Stem Cell Programme, MIRM. The findings, which are for the first time in the country, will now have significant implications in birth defect research and evaluation of developmental toxicity during drug screening. The study was supported and funded by Manipal University and the Stempeutics. The research findings concluded that embryonic stem cells have a lot more to offer besides therapy. While there are ethical issues limiting the study of molecular mechanisms underlying the pathogenesis in human embryos, the MIRM team used EB as a tool to understand the effect of the endotoxins on induction of lineages in a developing fetus. "A molecular analysis of the EB exposed to LPS indicated the complete silencing of expression for eight of the mesoderm tissue markers. The EBs were then tested for their ability to produce osteoblasts or bone tissues of mesoderm origin. As expected these EBs could not be differentiated to osteoblast. They had lost their ability to form functional osteoblasts cells," explained Dr. Deb.

Human embryonic stem cells are the gold standard for studying tissue formation. It will also allow to predict the effect of drugs and natural toxins that the growing foetus may accidentally get exposed to, while inside the womb, stated Dr. Deb.

The findings are published in the online version of the pioneering journal "Regenerative Medicine" and will appear in the January 2008 print issue.