A Research team from Indian Institute of Technology Guwahati led by Dr. Rajkumar P. Thummer, Assistant Professor, Department of Biosciences & Bioengineering, along with his research scholar Mr. Krishna Kumar Haridhasapavalan, have developed a ‘Recombinant Protein Toolbox’ comprising of six special proteins, which can be used to convert healthy skin cells or any somatic cells from an adult human body into heart cells, specifically cardiomyocytes. The heart cells created using this toolbox can have the same function as the original heart cells and can be used to regenerate damaged heart tissues. Importantly, this toolbox can facilitate the generation of autologous heart cells in a lab.
It is now well understood that a heart attack happens when a part of the heart is damaged. In some animals, like the Zebrafish, the heart can grow back after being damaged, but in humans, the heart usually gets scar tissue instead of growing back new heart cells. The only way to treat heart disease is with a new heart, but there aren’t enough hearts available for transplantation, and it can be hard to make sure the new heart is accepted by the body. Scientists around the world are studying ways to convert regular body cells into heart cells, which could help with regenerating damaged hearts. The challenge is that cells can change in ways that could be harmful. So, scientists need to find a better, safer way to do this.
Proteins produced from another source when applied can convert cells from one form to another in a process known as cellular reprogramming. This process involves the use of specific proteins, known as transcription factors, which can alter the expression of genes within a cell and direct it to take on a new cellular identity.
The IIT Guwahati team has successfully produced cell-permeant recombinant proteins that can convert skin cells to heart cells. A recombinant protein is a desired protein produced by engineered host cells in a laboratory using recombinant DNA technology. By exposing skin cells to these proteins, the IIT Guwahati researchers could ‘reprogram’ the cells and make them have the characteristics of heart cells. This process can be seen as ‘re-wiring’ the genetic program of the skin cells to be more like that of heart cells.
The team has collaborated with Dr Vishwas Kaveeshwar from the Central Research Laboratory at SDM College of Medical Sciences and Hospital in Dharwad, Karnataka, to validate the biological activity of the recombinant fusion proteins.
Explaining the details of their work, Dr. Rajkumar P. Thummer, Assistant Professor, Department of Biosciences & Bioengineering, IIT Guwahati said, “Recombinant protein-based cellular reprogramming is a promising alternative and the safest approach among other available non-integration approaches. As these proteins do not modify or alter the genome of the cells, the cells generated using this reprogramming approach have a high cell therapeutic value. Several challenges associated with the heterologous production of these recombinant proteins have been addressed in our six research publications in different journals.”
According to Krishna Kumar Haridhasapavalan, Research Scholar at IIT Guwahati, and first author of the papers published by the team, “The recombinant proteins can be delivered to target sites without the need of any harmful reagents. In addition to cardiac repair, these proteins can be studied for their role in various cancers as suppressors or promotors of tumour growth.”
The researchers have recently shared their results on the development of cell- and nucleus-penetrating versions of six cardiac reprogramming transcription factors in numerous international peer-reviewed journals including, Molecular Biotechnology, Applied Microbiology and Biotechnology, Bioprocess and Biosystems Engineering, Current Research in Biotechnology, Healthcare Research and Related Technologies Proceedings from NERC 2022, Scientific Reports, and Advances in Experimental Medicine and Biology.
It is notable that Mr Krishna was honoured with the ‘Augmenting Writing Skills for Articulating Research (AWSAR) Award 2021’ for his outstanding scientific writing, explaining this research. The award, which includes a prize of ₹10,000, was given by DST, Govt. of India, for his story titled ‘Love failure may or may not be fixed, but heart failure can definitely be fixed.’