Human stem cells used to create new type of biohybrid neural implant
Researchers at the University of Cambridge have developed a new type of neural implant that combines stem cells with electronics and has the potential to help amputees or those who’ve lost the use of their limbs.
Developments in implantable neurotechnology and cell therapy offer potentially effective treatments for those with injuries to the peripheral nervous system, that is, the nerves that lie outside the brain and spinal cord. Both try to restore function to paralyzed or amputated limbs by either bypassing the site of injury to interact with existing nerve cells or by replacing damaged cells with new ones.
However, there are drawbacks. Insofar as the replacement of damaged cells is concerned, transplanted neurons can struggle to establish functional connections. And electrodes can’t work effectively without healthy working cells to interface with, commonly due to scar tissue that has built up at an injury site. Moreover, current neurotechnologies lack the ability to interface with different types of neurons responsible for performing different functions.
A potential answer to these issues lies in a biohybrid device, one which combines human stem cells with bioelectronics to create a more effective neural interface. Now, researchers at the University of Cambridge have done just that, creating a groundbreaking new biohybrid device that can integrate with body tissues.
The device’s key ingredient is induced pluripotent stem cells (iPSCs), adult cells – usually skin or blood cells – that have been reprogrammed in a lab to become like embryonic stem cells, which can develop into any other type of cell. The researchers used iPSCs to create myocytes, the cells that are the building blocks of skeletal muscles. It’s the first time iPSCs have been used in a living organism in this way.
The iPSCs were arranged in a grid on microelectrode arrays (MEAs) so thin that they can attach to the end of a nerve. This generated a layer of myocytes that sat between the device’s electrodes and the living tissue. The researchers then implanted the biohybrid device into rats for testing. They attached the cell-covered side of the device to the severed ulnar and median nerves in the rats’ front legs. These nerves were chosen because they approximate injuries to human upper limb nerves and the associated loss of fine motor and sensory functions.
Compared with the control group, researchers found that the device integrated with the rat’s body and prevented the formation of scar tissue. Further, the iPSC-derived cells survived for four weeks following implantation, the first time that cells have survived an extended experiment of this kind.
“These cells give us an enormous degree of control,” said Dr Damiano Barone, co-author of the study. “We can tell them how to behave and check on them throughout the experiment. By putting cells in between the electronics and the living body, the body doesn’t see the electrodes, it just sees the cells, so scar tissue isn’t generated.”
After four weeks, researchers tested the implanted nerves and found that they behaved like normal nerves, indicating healthy neural physiology. While the rats did not regain movement to the paralyzed limb, the device could detect signals sent by the brain that control movement.
The new device could assist amputees, where the challenge is trying to regenerate neurons and rebuild damage to the nerve circuitry caused by injury or amputation.
“If someone has an arm or a leg amputated, for example, all the signals in the nervous system are still there, even though the physical limb is gone,” Barone said. “The challenge with integrating artificial limbs, or restoring function to arms or legs, is extracting the information from the nerve and getting it to the limb so that function is restored.”
The researchers say their device could overcome this problem by interacting directly with the neurons that control motor function.
“This interface could revolutionize the way we interact with technology,” said co-first author Amy Rochford. “By combining living human cells with bioelectronic materials, we’ve created a system that can communicate with the brain in a more natural and intuitive way.”
The device has advantages over standard, non-stem-cell neural implants. Its small size means it’s implantable using keyhole surgery, and the use of lab-produced stem cells makes it highly scalable.
“This technology represents an exciting new approach to neural implants, which we hope will unlock new treatments for patients in need,” said Dr Alejandro Carnicer-Lombarte, co-first author of the study.
The device will require further research and extensive testing before being used on humans, but it represents a promising development in neural implants. The researchers are working on optimizing the device and improving its scalability.
The study was published in the journal Science Advances.
New Atlas, 22 March 2023