Chinese researchers have devised a new technique for reprogramming cells from human urine into immature brain cells that can form multiple types of functioning neurons and glial cells. The technique, published today in the journal Nature Methods, could prove useful for studying the cellular mechanisms of neurodegenerative conditions such as Alzheimer’s and Parkinson’s and for testing the effects of new drugs that are being developed to treat them.
Stem cells offer the hope of treating these debilitating diseases, but obtaining them from human embryos poses an ethical dilemma. We now know that cells taken from the adult human body can be made to revert to a stem cell-like state and then transformed into virtually any other type of cell. This typically involves using genetically engineered viruses that shuttle control genes into the nucleus and inserts them into the chromosomes, whereupon they activate genes that make them pluripotent, or able to re-differentiate into another type of cell.
In 2008, for example, American researchers took skin cells from an 82-year-old patient with amyotrophic lateral sclerosis and reprogrammed them into motor neurons. Cells obtained in this way could help us gain a better understanding of such diseases. Grafts of patients’ own cells do not elicit an immune response, so this approach may eventually lead to effective cell transplantation therapies. But it also has its problems – it appears that the reprogramming process destabilizes the genome and causes mutations, and that iPSCs may therefore harbour genetic defects that render them useless.
Last year, Duanqing Pei of the Chinese Academy of Sciences and his colleagues reported that human urine contains skin-like cells from the lining of the kidney tubules which can be efficiently reprogrammed, via the pluripotent state, into neurons, glia, liver cells and heart muscle cells. Now they have improved on the approach, making it quicker, more efficient and possibly less prone to errors.
In the new study, they isolated cells from urine samples given by three donors, aged 10, 25 and 37, and converted them directly into neural progenitors. They then grew these cells in Petri dishes and drove them to differentiate into mature neurons that can generate nervous impulses, and also into astrocytes and oligodendrocytes, two types of glial cell found in the human brain. Finally, they transplanted the re-programmed neurons and astrocytes into the brains of newborn rats, and found that the cells had survived when they examined the brains a month later, but it remains to be seen if they can survive for longer, and if they integrate into the existing circuits to be become functional.
This isn’t the first time that one type of cell has been converted into another without going through the pluripotent stage – in 2010, researchers from Stanford converted mouse connective tissue cells directly into neurons. The new technique does have a number of advantages, however.
Instead of using a virus to deliver the reprogramming genes, the researchers used a small circular piece of bacterial DNA which can replicate in the cytoplasm. This not only speeds up the process, but also eliminates the need to integrate the reprogramming genes into the chromosome, which is one potential source of genetic mutation, but it’s still not clear whether these cells contain fewer mutations than those reprogrammed using viruses.
Even so, the technique also makes the procedure of generating iPSCs far easier and non-invasive, as the cells can be obtained from a urine sample instead of a blood sample or biopsy. The next logical step will be to generate neurons from urine samples obtained from patients with Alzheimer’s, Parkinson’s, and other neurodegenerative diseases and to determine the extent to which this new non-viral technique damages the DNA.
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