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Using electric stimuli to grow heart and brain cells

Cells of the heart and brain can be easily derived from stem cells in the lab, thanks to the efforts of a team of interdisciplinary researchers at the Indian Institute of Science (IISc), Bangalore.

Stem cells are undifferentiated cells that have the ability to transform into a variety of cell types. Stem cell 'differentiation' into different cell types has been achieved before in the laboratory, but it is usually mediated by specific chemical cocktails. Nutrients that are capable of stimulating cellular growth, known as 'growth factors', are added to stem cells in the lab. This allows the stem cells to grow and differentiate into a variety of cell types – bone cells, muscle cells, heart cells, or even nerve cells.

“If you have tissue loss or damage, what you can do is take your stem cells, grow it on a synthetic support in a lab setting to form a tissue, and implant it later in a patient,” says Greeshma Thrivikraman, one of the authors of the paper.

Besides this established process, stem cells can also be differentiated into nerve and heart cells by the application of physical forces, as shown by the team of IISc researchers. They have used electrical current to evoke cellular differentiation in stem cells.

“If you have nervous tissue damage following stroke, it is really hard to isolate adequate number of nerve cells from your body and transplant it into your brain. So instead, what we can do is isolate stem cells from blood or bone marrow and make them specialized to function as nerve cells. Then we transplant these cells to recreate the lost tissue,” explains  Thrivikraman.

Some tissues in our body, like our nervous and cardiac tissues, are 'electroactive'. They can convert electric signal to information, just like nerve cells transmit messages within the body using electrical signals. Instead of using growth factors, these researchers have used electrical pulses and stimulation to encourage the differentiation of the stem cell into heart and nerve cells. It’s a physical process, rather than a chemical process.

After extracting stem cells from human bone marrow, the researchers used two different modes of brief electric stimulation to transform the stem cells into two different types of cells – nerve cells and cardiac cells. “Usually the normal heart beats at a frequency of ~1hertz so we applied a similar electric field to the physiology of native heart”, explains Thrivikraman. “This caused the stem cells to specialize into  heart cells.”

To differentiate stem cells to a heart cells, the researchers used a brief pulsed electric current. For the nerve cells, they used a direct electric current. “It is very difficult to efficiently convert stem cells to functionally specialized cells via chemical route. This is because, the added chemicals can cause side effects to the neighboring healthy cells. On the contrary, physical methods can be localized to the affected area and it does not cause any ill-effects.,” says Thrivikraman.

The material used to transmit electrical impulses in the stem cells were gold nanoparticles. Through the process of 'electroactuation', where the electric current received by cells was converted to mechanical force, the stem cells were differentiated. Unlike other nanoparticles, electroactuated gold nanoparticles are chemically inert since they don’t react when they come in contact with the cell. They enable stem cell differentiation because of their ability to exert forces on the cytoskeleton of the cell.

When the stem cells were exposed to pulsed and direct electric current, they began to show morphological features and markers similar to those found in heart and nerve cells respectively. This type of nanomechanical intervention through electroactuation is an effective strategy to differentiate stem cells for tissue engineering and regenerative medicine. Thrivikraman imagines that if all these conditions can be mimicked in vitro, “in future when someone has a heart failure or a stroke, we can use their stem cells along with this particular type of stimulation to generate more nerve or heart cells and then implant them at the site of injury.”

About the author:

Giridhar Madras is a Professor at the Department of Chemical Engineering, Indian Institute of Science. Bikramjit Basu is a Professor at the Materials Research Centre, Indian Institute of Science. Greeshma Thrivikraman is a PhD scholar with the Laboratory for Biomaterials, Materials Research Centre and Centre for Nanoscience & Engineering Indian Institute of Science.


About the paper:

Title: Electrically driven intracellular and extracellular nanomanipulators evoke neurogenic/cardiomyogenic differentiation in human mesenchymal stem cells

Publication: Biomaterials, November, 2015