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bypassing the pluripotent stem cell stage May 2
SuChun Zhang center, professor of neuroscience in the School of Medicine and Public Health, talks with postdoctoral student Lin Yao in his research lab at the Waismam Center.
Photo: Jeff Miller
A UWMadison research group has converted skin cells from people and monkeys into a cell that can form a wide variety of nervoussystem cells without passing through the doitall stage called the induced pluripotent stem cell, or iPSC. IPSC cells can generate any cell type, which could be a problem for cellbased therapy to repair damage due to disease or injury in the nervous system.
In particular, the absence of iPSC cells rules out the formation of tumors by pluripotent cells in the recipient, a major concern involving stem cell therapy.
A second advance comes from the virus that delivers genes to reprogram the adult skin cells into a different and more flexible form. Unlike other viruses used for this process, the Sendai virus does not become part of the cells genes.
Progenitor cells grown from the skin of ALS or spinal muscular atrophy patients can be transformed into various neural cells to model each disease and allow rapid drug screening. . Eventually, the process could produce cells used to treat conditions like spinal cord injury and ALS.
Jianfeng Lu, Zhangs postdoctoral research associate at the UWMadison Waisman Center, removed skin cells from monkeys and people, and exposed them to Sendai virus for 24 hours. Lu then warmed the culture dish to kill the virus without harming the transforming cells. Thirteen days later, Lu was able to harvest a stem cell called an induced neural progenitor. After the progenitor was implanted into newborn mice, neural cells seemed to grow normally, without forming obvious defects or tumors, Zhang says.
Other researchers have bypassed the pluripotent stem cell stage while turning skin cells into neurons and other specialized cells, Zhang acknowledges, but the new research, just published in Cell Reports, had a different goal. Our idea was to turn skin cells to neural progenitors, cells that can produce cells relating to the neural tissue. These progenitors can be propagated in large numbers.
The research overcomes limitations of previous efforts, Zhang says. First, the Sendai virus, a kind of cold virus, is considered safe because it does not enter the cells DNA, and it is killed by heat within 24 hours. This is quite similar to the fever that raises our temperature to remove cold virus. Second, the neural progenitors have a greater ability to grow daughter cells for research or therapy. Third, the progenitor cells are already well along the path toward specialization, and cannot become, say, liver or muscle cells after implantation. Finally, the progenitors can produce many more specialized cells.
The neurons that grew from the progenitor had the markings of neurons found in the rear of the brain, and that specialization can also be helpful. For therapeutic use, it is essential to use specific types of neural progenitors, says Zhang. We need regionspecific and functionspecific neuronal types for specific neurological diseases.
Progenitor cells grown from the skin of ALS Lou Gehrigs disease or spinal muscular atrophy patients can be transformed into various neural cells to model each disease and allow rapid drug screening, Zhang adds.
Eventually, the process could produce cells used to treat conditions like spinal cord injury and ALS..