Building Entire Disease Models from Stem Cells

Stem cells are used in the field of regenerative medicine because of their ability to self-renew and produce more stem cells. Pluripotent stem cells are unique in their ability to generate any kind of cell in the body, except for cells that form a placenta. So where a red blood cell can only generate another red blood cell, a pluripotent stem cell is able to generate not only another pluripotent stem cell, but also any other cell in the human body.

With the ethical issue of pluripotent stem cells coming from embryos no longer a barrier to their use, the main restrictions in the use of pluripotent stem cells in regenerative medicine is the ability and cost of scaling up the stem cultures to a large enough size so as to create large systems for scientists to study. In order to generate and grow, the cells need a surface to attach to and additional nutrients to grow. So whilst scientists can grow a human ear on the back of a mouse, the ability to grow a larger organ such as a lung is much more challenging.

This is because the 2D cell culture, that is currently used to generate pluripotent stem cells, is not able to completely mimic the environment in which the cells grow in the human body. Furthermore, the number of cells that can be cultured in vitro in a laboratory using 2D cell culture is quite limited. This means not enough cells can be produced to create an entire system for scientists to study for clinical research, or to generate larger organs or systems for the purpose of curing someone.

Priyanka Gupta, a research scholar at IITB-Monash Research Academy, is looking at how to solve this problem through the use of bioreactors. A bioreactor is a system that is able to grow cells or tissue. Gupta’s research is seeking to create a bioreactor that copies the same environment in which the cells grow naturally inside the human body.

The research looks at the design of the bio-reactor system to determine the best model to recreate the environment in the human body. Her research also looks at all the conditions that are required, such as the amount of fluid and oxygen required, how the fluid flows within the system and how waste accumulates.

The various parameters involved in culturing any cell line and their effects change drastically when scientists scale up from the bench top to a much larger reactor scale. Furthermore, the smaller culture systems generated in vitro are not able to mimic the complex in vivo systems. A bioreactor is more capable of mimicking the environment in the body.

Gupta’s research focuses specifically on the various parameters and each of their effects on the culturing of stem cells and in scaling up production as well. The parameters that are being tests include the design of the reactors, the amount of media used, levels of oxygen concentration, rate of fluid flow and the effect of metabolites (such as glucose, amino acids and other growth factors, or ammonia which is a waste product). This research involves testing these parameters at a small scale, followed by selecting the parameters that have significant effects and testing them at a larger scale to determine what are the optimum conditions for the specific parameters to be used in the bioreactor system.

In scaling up to the bioreactor system there may be changes that are required to be made to the parameters due to the volume and type of system use to scale up. As a consequence some parameters are then evaluated further and tested to determine the optimal process.

Bioengineering of stem cells is a relatively new field and work is being done all around the globe in this area, but the data is still incomplete and the perfect solution yet to be reached.

IITB-Monash Research Academy is a Joint Venture between IIT Bombay and Monash University. Research scholars study for a dually-badged PhD from both institutions, and enrich their research and build collaborative relationships by spending time in Australia and India over the course of their degree. Established in 2008, IITB-Monash Research Academy aims to enhance scientific collaborations between Australia and India.

Overseen by IIT Bombay’s Professor Jayesh Bellare and Dr Sameer Jadhav, and Professor Paul Verma and Professor Kerry Hourigan from Monash University in Melbourne, this research will have a significant impact on the field of regenerative medicine.

Reflecting on her research Gupta said “Every one of us has seen someone near to us suffer from a disease which cannot be cured, and we would give anything to help them. This research will give scientists the tools so that they can fulfill this wish. It has the potential to give relief and happiness to people all around the world. This is the main reason why I believe that my research is of great importance.”

The bio-reactor will potentially allow scientists to recreate disease models, such as diabetes, so that they can be studied in more detail giving rise to the opportunity for a cure. Furthermore, in the case of degenerative diseases or organ failure, this technology will enable sufficient quantities of cells to be generated to potentially replace those that have been lost or even create entire organs.

There is also the possibility that this technology will be able to be used across animal species, for example used with IVF technology to breed endangered species. It is not unfeasible that one day Gupta’s research may help cure cancer, or save the life of a loved one.

Research scholar: Priyanka Gupta, IITB-Monash Research Academy

Project title: Parameter optimization and designing of bioreactor for the expansion of pluripotent stem cells

Supervisors: : Professor Jayesh Bellare, Dr Sameer Jadhav, Professor Paul Verma and Professor Kerry Hourigan

Contact details: priyankka.g@gmail.com

The above story was written by Ms Rakhee Ghelani based on inputs from the research student and IITB-Monash Research Academy. Copyright IITB-Monash Research Academy.