Using skin cells from adult siblings with schizophrenia and a genetic mutation linked to major mental illnesses, Johns Hopkins researchers have created induced pluripotent stem cells (iPS cells) using a new and improved "clean" technique.
Reporting online February 22 in Molecular Psychiatry, the team confirms the establishment of two new lines of iPS cells with mutations in the gene named Disrupted In Schizophrenia 1, or DISC1. They made the cells using a nonviral "epiosomal vector" that jumpstarts the reprogramming machinery of cells without modifying their original genetic content with foreign DNA from a virus.
The stem cells from these two new lines, the scientists say, can be coaxed to become brain cells such as neurons. Because they have the DISC1 mutation, they stand to play an important role in the screening of drugs for treatments of major mental illnesses such as schizophrenia, bipolar disorder and major depression, as well as provide clues about the causes of these diseases.
"Most people think of stem cells only as potential transplant therapy to replace damaged cells or tissue, but for psychiatric diseases, which have proven a challenge to scientific understanding just as a sheer cliff challenges a climber, these cells provide a toehold," says Russell L. Margolis, M.D., professor of psychiatry and neurology, and director of the Johns Hopkins Schizophrenia Program. "Nature put in only a few little grab holds, and now we are generating our own so we can scale the cliff of mental illness faster."
The benefit of maintaining the original genome of cells being reprogrammed outweighs the fact that the episomal vector approach is both time- and labor-intensive, says Guo-li Ming, Ph.D., associate professor of neurology, Institute for Cell Engineering, Johns Hopkins University School of Medicine.
"The efficiency of the new technique is very, very low," Ming reports, citing a rate of 0.0006 percent or l
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