Researchers from the Indian Institute of Technology (IIT) Guwahati have developed a special 'Protein Toolbox' which can be used to convert skin cells into heart cells, and hence, fix a damaged heart. Known as a 'Recombinant Protein Toolbox', it comprises six special proteins, and can be used to regenerate damaged heart tissues. 


The results have been published in the journals: Current Research in Biotechnology, Molecular Biotechnology, Bioprocess and Biosystems Engineering, Applied Microbiology and Biotechnology, and Scientific Reports.


What kind of heart cells are produced using this technique?


The six special proteins can be used to convert healthy skin cells or any somatic cells from an adult human body into heart cells. All the cells in the body apart from germ cells (sperm and egg cells) are called somatic cells. The heart cells generated using this technology are cardiomyocytes, which are the cells responsible for the contraction of the heart. In other words, cardiomyocytes are responsible for the beating of the heart. 


The cardiomyocytes produced using this tool box can perform the same function as the original heart cells, and can be used to regenerate damaged heart tissues. The toolbox can be used in laboratories to facilitate the generation of autologous heart cells. This means that an individual's own cells can be used to generate healthy heart cells. 


When a blocked artery prevents oxygen-rich blood from reaching a section of the heart, a heart attack occurs. If the blocked artery is not reopened quickly, the part of the heart normally nourished by that artery begins to die, and the longer a person goes without treatment, the greater the damage. 


In humans, the damaged heart cells, instead of growing back to new heart cells, form scar tissue. Unlike humans, zebrafish can regenerate their damaged heart cells. 


If someone has severe heart disease, and the heart damage cannot be reversed, the only way for the person to survive is heart transplantation. However, not enough hearts are available for transplantation. Moreover, even if heart transplantation is carried out, the graft might be rejected by the body. 


Therefore, converting regular body cells into heart cells to regenerate damaged hearts is an effective method. However, a challenge which most scientists face is that this procedure can cause cells to change in ways that could be harmful. Hence, it was important to find a better, safer way to conduct this procedure. 


The technique of converting skin cells to heart cells


According to Dr Rajkumar P Thummer, Assistant Professor, Department of Biosciences & Bioengineering, IIT Guwahati, and the lead researcher, the new technique is safer than other methods of regenerating damaged hearts because the toolbox consists of recombinant proteins. These are proteins with desired properties that are engineered inside a laboratory using recombinant DNA technology. The proteins are produced by engineered host cells. 


The process of using proteins produced from a particular source to convert cells from one form to another is known as cellular reprogramming. The proteins used to conduct this process are called transcription factors. They can alter the expression of genes within a cell, and direct the cell to take on a new cellular identity. 


The transcription factors used in the research belong to cardiac cells. 


As part of the new research, the team exposed skin cells to the transcription factors, in order to reprogramme the cells and convert them into cells which have the characteristics of heart cells. Therefore, it is a process of 'rewriting' the genetic programme of skin cells to make them behave like heart cells. 


Why the researchers chose skin cells to conduct the study


The IIT Guwahati team chose a type of skin cell called fibroblasts to conduct the research. 


"Fibroblasts are the most commonly used cells for cellular reprogramming. Most importantly, the main aim of this research is to develop a safer approach for direct cardiac reprogramming, which can then be used to reprogram cardiac fibroblasts into functional cardiomyocytes in an injured or a damaged heart," Thummer told ABP Live.


Cardiac fibroblasts are the cells which form scar tissues following a heart attack. 


According to Thummer, skin cells are not the only cells which can be reprogrammed into cardiomyocytes. Cardiac fibroblasts can also be rewritten into cardiomyocytes. 


How is the technique safer than other methods of regenerating damaged hearts?


Recombinant proteins are safe because they perform their intended function inside the nucleus of a cell, and eventually disappear over time, without leaving behind any toxic waste, unlike the genetic counterparts of the proteins, Thummer said. In this way, recombinant proteins are safe for cellular programming compared to other approaches.