Animal derived 'hanging drop' cells to help in liver studies

Dr. Shikha T Malik

The human body is a complex interplay of different organs with specialized functions. Scientists have been working for decades trying to understand normal functioning of the human body and in doing so they often look deeper into body structures of animals which mimic human organs like liver and heart. Using appropriate animal organ is particularly helpful in conducing toxicology and other studies relating to new drugs.

Among varied physiologic roles of liver are detoxification, metabolism and secretion of plasma proteins. Most of the liver is made up of cells called hepatocytes which are responsible for majority of its functions. In order to understand response of liver to drugs and toxins, scientists have to study these cells. Researchers want to understand biology in systems as close as possible to humans. This can be done by using hepatocytes either derived from humans or immortalized cell lines. There are many ways of culturing such cell lines but such lines are very different from the way cells are organized inside our body. In the body cells are like balls in a bag. They touch, talk and work with each other. This means cells should be organized in a three-dimensional manner for them to mimic their organization in human bodies.

A team of researchers led by S K Onteru at the National Dairy Institute, Karnal, has tried to establish a 3-D spheroids culture system of liver cells that mimics human liver more closely when compared to available 2-D arrangements. Researchers took cells from sheep and buffalo livers from slaughterhouses and cultured them in varying media and culture conditions and showed that in one of the conditions called 'Hanging Drop' method with a special medium, cells were very similar in their organization and gene make up as the freshly derived liver cells. In this method, there were no substrates onto which the cells adhered, the cells formed micro tissues under the gravitational force in the absence of any synthetic materials.

Cells in the hanging drop are more like the cells in human body. The DNA and protein analysis of human and cattle studies revealed a close resemblance between the two. The liver of humans, cattle, sheep and goat have also been shown to be very similar in structure, which makes it relevant to study human liver functions and response to drugs in these systems apart from small rodents like mice. The research group has shown that the sheep and buffalo cells can be maintained in such spherical hanging drops for 12 and 6 days respectively before they start losing the 3-D structure.

"Most of the liver is made up of cells called hepatocytes which are responsible for majority of its functions. In order to understand response of liver to drugs and toxins, "scientists have to study these cells."

The new culturing system is less expensive and closer to the human organ but a lot of obstacles need to be overcome before this system can be routinely used in the laboratory as a substitute to human derived primary cells or small animal models. 'Currently, the culture systems are being used for toxicology studies. If these studies are successful, we can use this system routinely in laboratories within 4-5 years,' feels Dr. Dheer Singh, one of the co- authors of the paper published in journal Scientific Reports. (India Science Wire)

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