Teams of the University of California – Los Angeles (UCLA) Health Sciences , USA, for the first time were able to turn human stem cells into sensory interneurons, responsible for the sense of touch. The technique, published January 11, 2018 in Stem Cell Reports, could be become the basis of stem cell therapy, which will help restore sensitivity in paralyzed patients.
Sensory interneurons, a class of neurons in the spinal cord, are responsible for the transmission of a signal that receives from the external and internal environment of the body sensitive neurons. Violation of this function in paralyzed people leads to a lack of tactile sensations, as well as insensitivity to pain, which can be the cause of burns and other domestic injuries.
“The field has for a long time focused on making people walk again,” – said Samantha Butler, the study’s senior author. “‘Making people feel again doesn’t have quite the same ring. But to walk, you need to be able to feel and to sense your body in space; the two processes really go hand in glove.”
In a study, published in September 2017 in the journal eLife, Butler and her colleagues determined how the signals from a family of proteins called bone morphogenetic proteins, or BMP, affect the development of sensory interneurons in chicken embryos. In the new work, scientists apply the findings to human stem cells in the lab.
Researchers added a specific BMP4 bone morphogenetic protein, as well as a signal molecule that helps regulate the formation of various types of tissues of a growing embryo called retinoic acid, to human embryonic stem cells.
As a result, the cells differentiated into a mixture of two types of sensory interneurons: dl1, which give people proprioception a sense of where their body is in space, and dl3, allowing to feel a sense of pressure.
The researchers found that an identical mixture of sensory interneurons develops by adding the same signal molecules to induced pluripotent stem cells (iPSC). These cells are created by reprogramming the patient’s own mature cells, such as, for example, skin cells.
IPSC can evolve into any type of body cells, while preserving the genetic code of the person from whom they were obtained. The ability to create sensory interneurons from the patient’s own reprogrammed cells without inhibiting the immune system can be a real breakthrough in cell therapy aimed at restoring sensitivity.
Butler hopes that she will be able to create a technique for obtaining one type of neuron at a time, which will simplify the definition of the functions of each cell type and will allow the clinical use of interneurons to begin to treat paralyzed people. However, its research team has not yet succeeded in determining how to make stem cells yield entirely dl1 or entirely dl3 cells. Perhaps, in this process another signal path is involved, she noted.
Researchers also have not yet determined the specific ratio of growth factors that stimulate stem cells to differentiate into other types of sensory interneurons.
At this stage of the work, the UCLA group implants the interneurons dl1 and dl3 into the spinal cord of mice to determine whether the cells are integrated into the nervous system and become fully functional. This is an important step in determining the clinical potential of cells.