Brain cells created directly from skin cells
BRISBANE: Researchers have transformed adult mouse skin cells directly into functional nerve cells, skipping the stem cell stage, in a huge step towards treating diseases such as Alzheimer's or spinal cord injuries.
"We actively and directly induced one cell type to become a completely different cell type," said pathologist Marius Wernig, from the Stanford University School of Medicine in California.
"These are fully functional neurons. They can do all the principal things that neurons in the brain do."
The technique could eventually be used to treat any condition where neurons need to be replaced, such as Alzheimer's or Parkinson's disease, or spinal cord injuries, said the study's lead author Thomas Vierbuchen, a stem cell researcher at Stanford University in Palo Alto, California.
Study nervous system diseases
The cells could also be used to study nervous system diseases caused by DNA mutations or to test new drugs, according to the study published today in the British journal Nature.
This is the first time scientists have turned one type of mature cell into another. Once a cell has differentiated - that is, it's turned from an immature cell into a brain cell or a skin cell or a liver cell - it stays as that type of cell until it dies.
But immature cells, or stem cells, have the ability to differentiate into any type of cell. Until now, scientists have been transforming cells back into the stem cell stage, which they call pluripotency.
Skipping the stem cell stage
This new process skips this stage, and in doing so it bypasses the ethical issues involved in using embryonic or embryo-like stem cells to produce patient-specific cells for regenerative medicine.
It also solves some of the practical problems involved in using cells produced via pluripotency, said the report's lead author Thomas Vierbuchen.
The scientists used a cell type called a fibroblast, found in the connective tissue and easily collected from skin biopsies, because they knew that mature, differentiated cells such fibroblasts could be made pluripotent by activating particular genes. The particular genes code for four transcription factors, compounds that control which genes are turned on or off in the cell.
Those pluripotent cells can then be coaxed to become other kinds of cells, such as neurons, that are genetically identical to the donor patient. This means they won't be rejected by the body's immune system if used to replace cells, but they can also produce tumors if a few pluripotent cells are implanted along with the new cell type, Vierbuchen said
By activating neuron-specific genes rather than stem-cell-specific genes, Vierbuchen and his colleagues think they can avoid that problem.
Only three genes were activated
The team investigated 19 genes, and found that they only needed to activate three genes, called Ascl1, Brn2 and Myt1l, to make functional neurons.
The new neurons, which could be created from both embryonic cells and cells taken from four-day-old mice, could form synapses with other cells and generate electrical pulses, called action potentials, to send messages along nerves, Vierbuchen said.
"We were pleasantly surprised by the quality of their functional properties, given the conditions under which they were derived," said Vierbuchen.
"Whether or not this process works similarly well in human cells is an important area of future research," Vierbuchen said
The three-gene combination almost exclusively made neurons producing the neurotransmitter glutamate, one of a set of chemicals neurons use to communicate with each other, so it will also be important to find which combinations of transcription factors make other kinds of neurons, he said.
Massimo Hilliard, a neuroscientist at the Queensland Brain Institute in Brisbane, Australia, said the finding was a milestone discovery, because it presented a possible way to generate patient-specific neurons without creating potentially tumor-producing pluripotent cells.
"The implications of the results of this work are enormous both for the neuroscience community as well as for the medical field," Hilliard said.