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Importance of 3D cell cultures in Modern Medicine

11/8/2021

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Around 18 months back, the pandemic caught us off guard and people across the globe suffered. What is termed as an incredible feat, we had the vaccines available for the public within a year. But have you wondered why it took such a long time to develop and approve a specific drug against COVID -19? Even in case of other deadly diseases like cancer, which claims countless lives every year, the failure rate of drugs in clinical trials is 97%. That means 97 percent of the time that a new drug is tested in a clinical trial for a particular type of cancer, it never makes it to the market. 
In this feature, we learn why this is the case. Drug discovery against a specific disease starts with screening thousands of molecules to choose possible drug candidates which are tested on animals before moving to the clinical trials. As animals are not a sustainable model to screen drugs, the alternative is to screen and test these drugs on cells grown as single sheets on surfaces in labs (2D culture). The major drawback of these systems is that they do not represent the complexity, structure and functioning of actual human tissues or organs. This makes them unreliable and unpredictable which ultimately leads to high failure rate in clinical trials.
Modern medicine, thus requires new efficient tools to battle the menace of diseases. This makes 3D cell cultures very important as they represent an in-vitro system with in-vivo characteristics, that means it carries advantages offered by both 2D systems and animal models. They offer a sustainable platform for a range of applications in biomedical research like drug based investigations and tumor research. Developments and innovations in 3D cell cultures will soon promote it as a mainstream tool in research. This would highly benefit the society to tackle the severity of deadly diseases.
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3D Cell Culture and its types.

11/8/2021

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​3D cell culture is an innovative technique to accurately model human tissues with massive potential in biomedical applications. Its unique ‘near to in-vivo’ characteristics makes it an attractive tool in fields such as drug development and testing, tissue engineering and cancer research to name a few.
Have you wondered how are cells cultured in three dimensions in a lab? Well, based on the application, there are broadly two types of 3D cell cultures depending on the use of scaffolds. Scaffolds are supporting elements that promote growth of cells in a well defined shape and structure to match the tissue of interest.
Scaffold free 3D culture -  This is a simplistic way of culturing cells in 3D where the cells are grown without using a scaffold and allowed to interact with each other and self-arrange to form clusters called spheroids. These spheroids recapitulate physiological characteristics of tissues with regard to cell-cell contact. In one such study at NRG, we developed lung cancer spheroids to evaluate a novel drug delivery method and showed that spheroids can be a suitable model for drug based investigations. 
Scaffold based 3D cell culture - This type of 3D cell culture is developed by providing scaffolds to cells for physical support on which they can attach and grow in a specific shape. The scaffolds can be of synthetic or natural origin and the choice of selection is dependent on the application. For instance, recognizing the limited treatment options in severe burn victims, we have developed an inexpensive, biocompatible and biodegradable scaffold to promote wound healing.
3D cultures are now being integrated with microfluidic chambers to construct in vitro organ-on-a-chip to model several diseases. With such disruptive innovations we will be better equipped to tackle the increasing global disease burden. 3D cell cultures, thus, have an enormous potential to have a positive impact on global health.

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Role of 3-Dimensional Cell Cultures in understanding Diseases

10/23/2021

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There exists a plethora of human diseases and conditions that are very complex to understand, like cancer. It has become very important to understand how a disease manifests, what drugs work in curing it and also predict how severe it can turn into. Today, researchers are constantly working towards deciphering the complexities of human diseases for betterment of global health. 
So how do researchers study human diseases? Surely it is not possible to use humans as lab rats. That’s why the scientific community uses some animals like mice to model the diseases. Believe it or not, these models have a lot in common with humans more than one thinks, genetically of course. For example, 85% of mice DNA is similar to humans. So, scientists can take a bet that if one thing is occurring in humans, there’s a 85% chance that it happens in a mouse too. Although these models help reveal a lot about human conditions, they have their own limitations for other applications like drug discovery.
In a quest to search for sustainable models that offered better accuracy, scientists turned to studying human cells in-vitro i.e. in the lab. Take the example of HeLa cells, the lung cancer cells obtained from a woman, Henrietta Lacks in 1951 (Watch Famous Hollywood Movie here). These cells are widely used to study different aspects of lung cancer till date.  Now, the simplest way to study these cells is by growing these cells in a plate. As most human cells attach themselves to the surface of the container the model is two dimensional (2D). Although human in nature, such a model does not resemble the workings of the human body and thus we cannot rely on the results obtained, especially in drug testing. 
But as we have heard, Necessity is the mother of all inventions! The limitations of both the animal models and in-vitro studies led to the development of 3D cell culture. This novel type of cell culture allows the cells to grow & interact with the environment just like they do inside the human body (in-vivo). Offering benefits of both in-vitro and in-vivo conditions, 3D culture has gained a lot of popularity for a wide range of applications. For instance, at Nanomedicine Research Group, we have developed 3D culture of lung cancer cells to test a novel nanoparticle based drug delivery method. In a separate study, we developed biocompatible structures to support and assemble skin cells in its native architecture as an attempt for wound healing.
What does this mean for the future? 3D cell culture offers high throughput screening of many drug candidates which would result in better precision in drug discovery. Researchers are also looking at the prospect of developing different disease models using 3D cell culture to get a better understanding of the disease. Such advancements give a better hope for the future of global health!
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Nanotechnology and its Role in Medicine

10/20/2021

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NANOTECHNOLOGY! A rather complex looking word has more applications in our day to day life than one  thinks? Nanotech, short for nanotechnology, is a technology operating at a nanoscale i.e. a scale of one billionth of a metre. To visualize this, imagine seeing through the eyes of an elephant to operate at the level of an ant! 

The fascinating benefits of nanotechnology have led to its applications in a variety of sectors. For instance, many new electronic appliances like smartphones and TV; that have screens, use OLEDs (organic light-emitting diodes) that are made from nanostructured polymers. OLEDs offer better brightness and picture quality. Nanotechnology is also used in automotives to manufacture highly powerful rechargeable batteries that are being employed in electric vehicles (EVs) like Tesla. It has found its use in the textile and cosmetics industries as well. 
The story doesn’t end here! Nanomedicine is the field of medicine where nanotechnology is employed to help improve & even revolutionize finding, anticipating, and treating a wide range of diseases. For instance, researchers have developed novel techniques to deliver medication using nanotech for deadly diseases like cancer. These techniques are highly efficient and also minimize the amount of  medication required. An example of nanomedicine with which everyone can relate is the mRNA vaccine for COVID-19. The vaccines make use of lipid nanoparticles to effectively transport the mRNA to the right place in the cells. Nanotech also plays an important role in regenerative medicine to design human tissues and organs. 
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Now you must be wondering, if nanomedicine demonstrates such promising qualities, why isn’t it being used frequently in clinics? The main reason for this is, no matter how great a nanomedicine innovation looks in research labs, its application depends on the manufacturability of the nanomaterial. That means the industry producing the nanomaterial should produce it effectively given its design, cost, and distribution requirements. A major problem faced by the industries is scaling up production as it requires innovative manufacturing practices. In the case of COVID-19, we were able to produce the vaccines in a short period because of disruptive innovations funded from government and private sectors. 
So what’s next? To facilitate this, researchers are now focused on providing innovative and affordable solutions to make the manufacturing technologies commercially viable which would subsequently benefit the pharmaceutical industry and society as a whole. 

Still interested? See this video to get more insights :
https://www.youtube.com/watch?v=dqy6O68yxmg
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The story of Insulin

11/20/2019

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​“Laughter is the best medicine - unless you are diabetic, then insulin comes pretty high on the list” – Jasper Carrott
Remember the medicine the doctor says your elderly grandparent has to take every now and then for diabetes sugar control? That medicine is insulin, one of the earliest success stories of the biopharmaceutical industry.
Insulin is a hormone or a signalling chemical which is produced in the beta cells of our pancreas. It regulates the levels of energy molecules like glucose in our blood by forcing the excess glucose to get absorbed into the liver, adipose tissue and skeletal muscles. The beta cells secrete insulin when there is high blood sugar level and don’t secrete anything when the sugar levels are low. The neighbours of beta cells are the alpha cells which do the opposite work of the beta cells by secreting the polar opposite of insulin, known as glucagon which promotes the release of stored sugars when sugar levels are low in blood.
The human insulin protein is made of 51 amino acids (the building blocks of proteins) and consists of an A chain and B chain which are linked together by disulphide bonds. It is 5808 times heavier than a hydrogen atom. Insulin was discovered way back in the early 20th century by a team of biologists at the University of Toronto and this discovery was recognized in the 1923 Nobel Prize for Physiology or Medicine. The entire sequence of amino acids which comprise insulin was first found out by the British biochemist Frederick Sanger for which he was awarded the Nobel Prize in Chemistry in 1958. The crystal structure of Insulin in the solid state was first discovered by the pioneering crystallographer and 1964 Nobel laureate in Chemistry Dorothy Crowfoot Hodgkin.
Purified insulin obtained from animals was the only known cure for treating diabetes for a long time. This was however difficult to come by in significant amounts and was inaccessible to much of the patient population. However, due to Sanger’s discovery of the Insulin structure, things began to change. insulin was first synthesized in the laboratories of Helmut Zahn and Panayotis Katsoyannis simultaneously in the 1960s. In 1978, genetically engineered human insulin was first synthesized using E. coli cells by biotechnologists Arthur Riggs and Keiichi Itakura of Beckman Research Institute and Herbert Boyer of Genentech. In 1982, Genentech went on to sell the first vials of biosynthetic human insulin under the brand name of “Humulin”. Today Insulin is produced either in genetically engineered yeast or E. coli cells. In India, Biocon is the main player of the insulin market.
Since its inception, insulin research has attracted people from diverse fields such as biology, chemistry, biochemistry, pharmaceutics, chemical engineering, biotechnology etc. The biochemists identified the structure while the molecular biologists pondered over how to get microbes to produce human insulin by tinkering with their genes. The cell biologists worked on how to culture those cells to get high yields and good quality of insulin while the biotechnologists designed the huge bioreactors required for production. The chemical engineers came up with and designed the separation strategy for fishing out insulin from the large amount of soup generated in the bioreactor. The analytical chemists checked the quality of the product while the pharmacists worked on various formulations for stabilizing the product.
The success story of Insulin in treating diabetes which is a major cause of concern in India due to the high number of cases recorded each year is heartening. The success was due to the team efforts and collaboration of many scientists and engineers who tackled chunks of the larger problem. Similar success stories are in the pipeline of the biopharmaceutical industry.
Keeping the importance of collaborative work between various disciplines for future successes in mind, the Institute of Chemical Technology, Matunga, Mumbai is organizing a biosimilars workshop during 29th November to 1stDecember,2018. This workshop will familiarize the participants on the challenges related to making life saving molecules such as Insulin and the newer molecules being targeted by the biopharmaceutical industry.
Be a part of the future success stories !!
Sai Vivek Prabhala, Final Year B Chem Engg., Department of Chemical Engineering, Institute of Chemical Technology, Mumbai
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