A research group at the Salk Institute in San Diego has discovered a new protocol for converting umbilical cord blood cells into neuron-like cells. These new cells could prove valuable for the treatment of a wide variety of neurological conditions, including stroke, traumatic brain injury and spinal cord injury.
Physicians have used umbilical cord blood for more than 20 years to treat many different types of illnesses, including cancer, immune disorders, and blood and metabolic diseases. However, these Salk Institute researchers demonstrated that cord blood (CB) cells can be differentiated into cell types from which brain, spinal and nerve cells arise.
Juan Carlos Izpisua Belmonte, a professor in Salk’s Gene Expression Laboratory, who led the research team, said: “This study shows for the first time the direct conversion of a pure population of human cord blood cells into cells of neuronal lineage by the forced expression of a single transcription factor.”
Izpisua Belmonte’s group used an engineered retrovirus to introduce a gene called Sox2, a transcription factor that acts as a switch inside cells that converts them into neurons. Therefore, by introducing Sox2 into CB cells, and culturing them in the lab, the cells formed colonies that expressed genes normally found in neurons.
Were these cells actual neurons or faux neurons? Cells might make neuron-specific genes, but they do not assemble those gene products into neuron-specific machinery, then they are not neurons. To if such cells are neurons, they should be able to manipulate the electrical charges across their cell membranes. But subjecting cells to electrophysiological tests, they determined that these new cells, which they called induced neuronal-like cells or iNCs, could transmit electrical impulses. This shows that the iNCs were mature and functional neurons. Next, they implanted these Sox2-transformed CB cells to a mouse brain and found that they integrated into the existing mouse neuronal network and were capable of transmitting electrical signals like mature functional neurons.
Mo Li, a scientist in Belmonte’s lab and a co-first author on the paper, said: “We also show that the CB-derived neuronal cells can be expanded under certain conditions and still retain the ability to differentiate into more mature neurons both in the lab and in a mouse brain. Although the cells we developed were not for a specific lineage-for example, motor neurons or mid-brain neurons-we hope to generate clinically relevant neuronal subtypes in the future.”
Scientists can use these cells in the future to model neurological diseases such as autism, schizophrenia, Parkinson’s or Alzheimer’s disease.
CB cells offer several advantages over other types of stem cells. First, they are not embryonic stem cells and are not controversial. They are more plastic, or flexible, than adult stem cells from sources like bone marrow, which may make them easier to convert into specific cell lineages. The collection of CB cells is safe and painless and poses no risk to the donor, and they can be stored in blood banks for later use.
“If our protocol is developed into a clinical application, it could aid in future cell-replacement therapies,” said Li. “You could search all the cord blood banks in the country to look for a suitable match.”