One of the many obstacles that have to be overcome before human embryonic stem cells can reach their therapeutic potential is to establish whether or not transplanted cells can be functionally integrated into tissues or organs.

According to a study by a team of Wisconsin scientists that is published in the Proceedings of the National Academy of Sciences, neurons that have been forged in the lab from blank slate human embryonic stem cells that have been implanted into the brains of mice, can successfully merge with the brain’s wiring and both transmit and receive signals.

Neurons are the most elementary functional unit of the central nervous system and are specialized cells that conduct impulses. The human brain has approximately 100 billion neurons that constantly transmit and receive the signals, which govern every process from walking and talking to thinking. The finding represents a vital stepping-stone towards using customized cells to repair a damaged or diseased brain, which is the most complex human organ.

Jason P. Weick, lead author of the new study and staff scientist at the University of Wisconsin-Madison’s Waisman Center explains:

“The big question was can these cells integrate in a functional way. We show for the first time that these transplanted cells can both listen and talk to surrounding neurons of the adult brain.”

The research team evaluated their lab-grown neurons’ ability to integrate into the brain’s circuitry by transplanting the cells into the hippocampus of adult mice. The hippocampus is a well-known area of the brain that plays a vital role in memory processing and spatial navigation. The researchers took live tissue taken from the animals that received cell transplants to study the cells capacity to integrate.

Weick and his team also observed that the human neurons adopted the rhythmic firing behavior of many brain cells communicating with each other in unison, and most significantly, that the human cells were able to alter the way the neural network behaved.

The researchers were able to answer this question by using a new technology known as optogenetics, in which light is used instead of electric current to stimulate the neurons activity.

Weick comments:

“Previously, we’ve been limited in how efficiently we could stimulate transplanted cells. Now we have a tool that allows us to specifically stimulate only the transplanted human cells, and lots of them at once in a non-invasive way.”

He explains that in order to determine the function of implanted cells, it was necessary to first modulate the capacity of the implanted cells as earlier technologies were too inaccurate and unreliable to determine precisely what transplanted neurons were doing.

All 220 types of tissue within the human body are derived from embryonic stem cells and their closely related induced pluripotent stem cells. In the lab, scientists have directed these cells to turn into many cell types, including brain cells.

The interest in human embryonic stem cells and induced pluripotent cells has the potential to produce unlimited supplies of healthy, specialized cells that can be used to replace diseased or damaged cells.

Scientists believe that brain disorders, such as amyotrophic lateral sclerosis, better known as Lou Gehrig’s disease and Parkinson’s disease could potentially be eradicated by replacing faulty cells with healthy lab grown cells.

In the past decade, numerous studies in animal models have demonstrated that both induced and embryonic stem cells are able to alleviate deficits of those disorders in animal models.

The new study paves the way for clinicians to potentially use light-based technology to manipulate transplanted cells and tissue.

Su-Chun Zhang, a UW-Madison professor of neuroscience and author of the new PNAS report, states:

“The marriage between stem cells and optogenetics has the potential to assist in the treatment of a number of debilitating neurodegenerative disorders. You can imagine that if the transplanted cells don’t behave as they should, you could use this system to modulate them using light.”

Another author of the PNAS report, funded by the U.S. National Institutes of Health, is Yan Liu who is also of UW-Madison’s Waisman Center.

Written by Petra Rattue