Potential of In vitro lung model in studying COVID-19 infection

Work done at Eyestem Research, Centre for Cellular and Molecular Platforms (C-CAMP), Bengaluru.

About author

Harshini Surendran completed B.Tech (Biotechnology) from PSG College of Technology, Anna University. She then started her research career with Prof. Prabha Sampath at Institute of Medical Biology (IMB), ASTAR, Singapore in the area of translation control of disease. Upon return she joined the Manipal Institute of Regenerative Medicine, Manipal Academy of Higher Education, Bangalore as Research Fellow to work on pluripotent stem cells-based modelling of lung development. At Eyestem, she worked on creation of an alternative and advanced in vitro model for understanding pathophysiology of SARS-CoV-2 infection and for screening of anti-COVID drugs. Currently, she is taking care of the ongoing work on developing novel strategies for selection and enrichment of retinal pigment epithelial (RPE) cells targeted for Age-related Macular Degeneration (AMD).

Interview

How would you explain your research outcomes to the non-scientific community?

The COVID-19 pandemic has created a huge impact on everyone’s lives as well as the global economy. One of the main drawbacks to developing drugs against COVID-19 is the lack of a suitable model recapitulating the disease biology. Immortalized primary and lung cancer cell lines have been traditionally used for drug screening. However, the application of such conventional in vitro models are limited by many disadvantages. That is where human pluripotent stem cell-derived lung cells will prove to be extremely useful. We investigated and found that this in vitro platform is a suitable model system for better understanding of the disease pathology and for testing new drugs against COVID-19.

How do these findings contribute to your research area?

Since 2016, I have been researching to understand the mechanism of lung (distal-proximal) patterning employing distal alveolar and proximal airway cells differentiated from iPSCs. I am also investigating the potential of alveolar progenitor cells in animal models of idiopathic pulmonary fibrosis. When COVID-19 was declared a pandemic in 2020, we repurposed it to focus on testing these lung lineage cells as a screening platform for SARS-CoV-2 infection. The successful outcome of this project opens up further opportunities to study diseases like influenza (common flu) caused by H1N1 and H5N1 viruses. Taken together our findings promise to make a significant contribution toward understanding the pathobiology of pulmonary infectious and other lung disorders.

“The successful outcome of this project opens up further opportunities to study diseases like influenza (common flu) caused by H1N1 and H5N1 viruses. “

What was the exciting moment during your research?

I joined as a Junior Research Fellow in Dr. Rajarshi Pal’s lab soon after my B. Tech degree and started working on pluripotent stem cells which were highly captivating. Culturing human stem cells in an undifferentiated state and forming embryoid bodies (EB – embryo-like structures containing germ lineages- ectoderm, endoderm, and mesoderm) was very fascinating to me. Though I had read theoretically, seeing different kinds of cells originating from a single EB became my first exciting moment.

In 2021, the 2nd wave of COVID-19 had its impact on me and most of my colleagues. All of us had usual symptoms like fever, throat pain, fatigue, loss of taste and smell, etc. Interestingly, in our experiments, SARS-CoV-2 infected lung cells evoked chemosensory changes in addition to triggering a massive inflammatory and anti-viral response. I was very excited to report this unique finding and was even more satisfied after we were able to establish a correlation between in vitro and in vivo results.

What do you hope to do next?

Lung disease is one of the leading causes of morbidity and mortality worldwide. Annually, more than 1 billion people suffer from either acute or chronic respiratory conditions. With the rare ability to generate different lung cell types, I would like (or try at least) to solve some of the debilitating lung diseases like pulmonary fibrosis and cystic fibrosis either by employing cell replacement therapy or gene editing technology. Additionally, this in vitro model is going to offer enormous opportunities for researchers who are involved in lung research.

Where do you seek scientific inspiration from?

Several articles get published every other day in line with what I’m trying to do. I usually get inspired and motivated by reading the new and better articles. I like to concentrate more on the discussion and limitation sections which helps me in building my hypothesis towards what is lacking. And whenever the results are supportive of my hypothesis, it pushes my efforts even further.

How do you intend to help Indian science improve?

Indian science has advanced significantly in recent years. But still there is a lack of multidisciplinary holistic approaches leading to failure in translation of basic research. I think communicating my science to people from a different background will help bridging the gap. I like sharing my exciting moments with high school students, encouraging them to pursue science as a career. I strongly believe that if nurtured properly young minds can generate great ideas which would be very beneficial for the country!

Reference

Surendran, H., Kumar, S., Narasimhaiah, S., Ananthamurthy, A., Varghese, P. S., D’Souza, G. A., Medigeshi, G., & Pal, R. (2022). SARS-CoV-2 infection of human-induced pluripotent stem cells-derived lung lineage cells evokes inflammatory and chemosensory responses by targeting mitochondrial pathways. Journal of cellular physiology, 10.1002/jcp.30755. https://pubmed.ncbi.nlm.nih.gov/35460571/

https://onlinelibrary.wiley.com/doi/full/10.1002/jcp.30755

Edited by: Nikita Nimbark

Meet the managers

Surabhi Sonam

Surabhi Sonam is an Assistant Professor. Along with teaching and research, she has a very strong interest in science communication. She has written several poems and blogs to communicate scientific principles and concepts. She is also volunteering with several science communication platforms as a content contributor and content editor. Under her supervision, her students have launched a scicomm magazine, Scinion which represents science in verbal and visual forms.

Sejal Dixit

Sejal Dixit is currently a 3rd-year student pursuing BSc triple majors in biotechnology, zoology, and chemistry from CHRIST (Deemed to be University). She loves to read, be it short stories, novels, magazines, or research articles. She is working with her college professor on a few papers, and wishes to pursue her master’s degree in stem cells and regenerative medicines. She has no problem socializing with new people and possesses leadership qualities. Her hobbies are dancing and traveling.

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