The researchers write about their work in the 5 October online issue of Cell Stem Cell.
Much of the stem cell research that is going on into making new brain cells focuses on using stem and adult cells from other parts of the body and reprogramming them to form new brain cells and then implanting them into the brain.
For example, earlier this year, Stanford researchers in the US reported how they converted mouse skin cells directly into neural precursor cells, the cells that go on to form the three main types of cell in the brain and nervous system.
But corresponding author of this latest study, Benedikt Berninger, now at the Johannes Gutenberg University Mainz, says they are looking at ways of making new neurons out of cells that are already in the brain.
"The ultimate goal we have in mind is that this may one day enable us to induce such conversion within the brain itself and thus provide a novel strategy for repairing the injured or diseased brain," says Berninger in a press release.
A major challenge of finding cells already in the brain that can be coaxed into forming new neurons, is whether they will respond to reprogramming.
The cells that Berninger and colleagues are focusing on are called pericytes. These cells are found close to blood vessels in the brain and help maintain the blood-brain barrier that stops bacteria and other unwanted material crossing from the bloodstream into the brain.
In other parts of the body, pericytes help with wound healing, which is what drew the team's attention:
"Now, we reason, if we could target these cells and entice them to make nerve cells, we could take advantage of this injury response," says Berninger.
They managed to coax adult human brain pericytes into neuron-like cells with the help of two genes, Sox2 and Mash1:
"Here we show that cells from the adult human cerebral cortex expressing pericyte hallmarks can be reprogrammed into neuronal cells by retrovirus-mediated coexpression of the transcription factors Sox2 and Mash1," write the researchers.
They used a method called "genetic fate mapping" in mice to confirm that the new brain cells had come from pericytes.
When they tested the new cells to see how closely they resembled neurons, they found they could produce electrical pulses and reach out to other neurons, two important features for being able to integrate into neural networks.
There is still a long way to go before what works in the test tube can be made to work in living tissue, but nonetheless, this is an important step in the search for a new way to make brain cells, say the researchers in their conclusions:
"While much needs to be learnt about adapting a direct neuronal reprogramming strategy to meaningful repair in vivo, our data provide strong support for the notion that neuronal reprogramming of cells of pericytic origin within the damaged brain may become a viable approach to replace degenerated neurons."
"Our results raise the possibility of functional conversion of endogenous cells in the adult human brain to induced neuronal fates," they write.
Reference
"Reprogramming of Pericyte-Derived Cells of the Adult Human Brain into Induced Neuronal Cells"; Marisa Karow, Rodrigo Sánchez, Christian Schichor, Giacomo Masserdotti, Felipe Ortega, Christophe Heinrich, Sergio Gascón, Muhammad A. Khan, D. Chichung Lie, Arianna Dellavalle, and others; Cell Stem Cell, 11(4) pp. 471 - 476, published online 5 Oct 2012; DOI:10.1016/j.stem.2012.07.007; Link to Abstract
Additional Source: Cell Press.
Much of the stem cell research that is going on into making new brain cells focuses on using stem and adult cells from other parts of the body and reprogramming them to form new brain cells and then implanting them into the brain.
For example, earlier this year, Stanford researchers in the US reported how they converted mouse skin cells directly into neural precursor cells, the cells that go on to form the three main types of cell in the brain and nervous system.
But corresponding author of this latest study, Benedikt Berninger, now at the Johannes Gutenberg University Mainz, says they are looking at ways of making new neurons out of cells that are already in the brain.
"The ultimate goal we have in mind is that this may one day enable us to induce such conversion within the brain itself and thus provide a novel strategy for repairing the injured or diseased brain," says Berninger in a press release.
A major challenge of finding cells already in the brain that can be coaxed into forming new neurons, is whether they will respond to reprogramming.
The cells that Berninger and colleagues are focusing on are called pericytes. These cells are found close to blood vessels in the brain and help maintain the blood-brain barrier that stops bacteria and other unwanted material crossing from the bloodstream into the brain.
In other parts of the body, pericytes help with wound healing, which is what drew the team's attention:
"Now, we reason, if we could target these cells and entice them to make nerve cells, we could take advantage of this injury response," says Berninger.
They managed to coax adult human brain pericytes into neuron-like cells with the help of two genes, Sox2 and Mash1:
"Here we show that cells from the adult human cerebral cortex expressing pericyte hallmarks can be reprogrammed into neuronal cells by retrovirus-mediated coexpression of the transcription factors Sox2 and Mash1," write the researchers.
They used a method called "genetic fate mapping" in mice to confirm that the new brain cells had come from pericytes.
When they tested the new cells to see how closely they resembled neurons, they found they could produce electrical pulses and reach out to other neurons, two important features for being able to integrate into neural networks.
There is still a long way to go before what works in the test tube can be made to work in living tissue, but nonetheless, this is an important step in the search for a new way to make brain cells, say the researchers in their conclusions:
"While much needs to be learnt about adapting a direct neuronal reprogramming strategy to meaningful repair in vivo, our data provide strong support for the notion that neuronal reprogramming of cells of pericytic origin within the damaged brain may become a viable approach to replace degenerated neurons."
"Our results raise the possibility of functional conversion of endogenous cells in the adult human brain to induced neuronal fates," they write.
Reference
"Reprogramming of Pericyte-Derived Cells of the Adult Human Brain into Induced Neuronal Cells"; Marisa Karow, Rodrigo Sánchez, Christian Schichor, Giacomo Masserdotti, Felipe Ortega, Christophe Heinrich, Sergio Gascón, Muhammad A. Khan, D. Chichung Lie, Arianna Dellavalle, and others; Cell Stem Cell, 11(4) pp. 471 - 476, published online 5 Oct 2012; DOI:10.1016/j.stem.2012.07.007; Link to Abstract
Additional Source: Cell Press.
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