Brain Cell Regeneration through Biocompatible Hydrogel Matrices

Picture Credit: Subhadeep

Our bodies are miraculous in that injured and damaged cells repair themselves and regenerate constantly. Stem cells, which are undifferentiated biological cells that self-renew and develop into different cell types, are a versatile cell source for therapeutic applications in regeneration of diseased or injured tissues. But so far, regenerating damaged cells in the brain remains the Holy Grail. For neurodegenerative diseases like Parkinson’s that cannot be cured with drugs, current therapies only work to supress symptoms. Cell transplantation therapy asdasd asd holds the potential to cure the disease from the root, but has met with very limited success because of the low survival rate of transplanted cells.

Picture Credit: Subhadeep

A major roadblock in stem cell based therapy for brain tissue engineering is the absence of proper matrices or scaffolds that would be aid the development of neurons from stem cells, without triggering a massive immune reaction when implanted in brain. Besides this, ideally the delivery of such a matrix into a patient’s brain would be minimally invasive.

Subhadeep Das, a research scholar at the IITB-Monash Research Academy, is addressing both these problems in his doctoral work. His goal is to develop a biocompatible scaffolding to support cell growth and development in the brain.

Using a truly interdisciplinary approach, Das has developed hydrogels from a special class of proteins called amyloids, which provide scaffolding for stem cells to develop into neurons, when implanted in the brain.

“We have developed self-assembled amyloid based hydrogels that promotes differentiation of mesenchymal stem cells to neurons,” said Das. “Moreover, these hydrogels do not elicit high inflammatory reactions when implanted in brain.”

Mesenchymal stem cells are a class of stem cells stored in bone marrow. Upon the introduction of proper physical and biochemical cues these stem cells migrate to regions of damage and start generating a particular kind of cell. The work builds on several attempts across the world to develop the kind of matrix that would mimic natural tissue. Scientists have tried developing different polymer based systems to mimic the natural extra cellular environment and provide the cells appropriate physical and biochemical signals for development, but met with limited success.
Das and his lab hope that the development of biocompatible scaffolds to support the cells by providing a suitable microenvironment could help in successful cell transplantation and curing the disease.

Teaming up with peptide chemists, material scientists, stem cell biologists and physiologists, Das has managed to develop robust and smart hydrogel systems based on amyloid nanofibres. These hydrogels are injectable and could be delivered into the target site with minimally invasive surgery. Das’s gels are not just smart systems, they’re also biodegradable, so they won’t stay in the brain indefinitely. The researchers already have preliminary proof that found the material is not attracting many immune cells and is within tolerance level both in in vitro and in animal models. They have successfully transplanted stem cells with this matrix into a Parkinson’s animal model and are assessing the fate of the transplanted cells. “When we transplanted the cells we were pleased to see that our success rate was better than we’d dared hope. We have evidence they’re going toward neurons,” said Das. The scientists are hopeful that the cells will turn into the particular class they need. “It is beyond doubt that stem cell therapy is going to change the landscape of medicine. But these magic cells are difficult to control and success in therapy requires their steadfast manipulation. Developing the material for stem cell manipulation and neuron could improve millions of lives, which is very exciting and motivating,” said Das.
Das is conducting his research at the IITB-Monash Research Academy, which operates a graduate research program in Mumbai. The IITB-Monash Research Academy is a Joint Venture between IIT Bombay, India and Monash University, Australia. Opened in 2008, the IITB-Monash Research Academy operates a graduate research program located in Mumbai that aims at enhancing research collaborations between Australia and India. Students study for a dually-badged PhD from both institutions, and spend time during their research in both India and Australia.

Research scholar: Subhadeep Das, IITB-Monash Research Academy

Project title: Engineering Amyloid Fibrils for Nanotechnology and Neuronal Cell Regeneration.

Supervisors: Dr. Samir Maji, Dr. John Forsythe.

Contact details: subhadeep@iitb.ac.in, subhadeep.das@monash.edu

Contact research@iitbmonash.org for more information on this, and other projects.