Breakthrough in cell conversion could help with Parkinson's treatment
A team of University at Buffalo researchers has identified a key obstacle in the cell conversionprocess, the manipulation of which allows for much easier transitions between cell types. The breakthrough has big implications for the treatmentof Parkinson's disease, with scientists able to create functionalneurons to replace those damaged by the condition.
Parkinson's disease is a degenerativedisorder that involves the loss of dopamine neurons in the brain, having a significant impact on the patient's motor skills. The newstudy has seen researchers attack the problem head on, attempting tofind an efficient method of producing new dopamine neurons, whichcould then be transplanted into the patient's brain to help tacklethe disease.
In the past, researchers have usedembryonic stem cells for the purpose, but not only is the materialdifficult to obtain, but making dopamine neurons from stem cells istime-consuming and doesn't result in a large enough volume of cells.Researchers have also turned to normal cells, such as skin cells, forconversion, but tested methods have suffered from similar issues,with too small a quantity of dopamine neurons being produced.
The new method takes a similarapproach, but benefits from a significant breakthrough made by the Buffalo team. In essence, the researchers were able toidentify a key obstacle to cellular conversion, which having beendiscovered can now be manipulated.
The team identified that atranscription factor protein, known as p53, guards against changeswithin a cell from one type to another, preventing any conversion.Once the expression of the protein was lowered, cell reprogrammingbecame much more effective.
Cells have the same basic source code,with that code being read differently to generate all cell types inthe body. Therefore, identifying p53 as the agent that maintains thestatus quo is significant to cell biology as a whole.
"It proves that we can treat the cellas a software system, when we remove barriers to change," says senior paper author Jian Feng. "We might be able able to playwith the system more quickly and we might be able to generate tissuessimilar to those in the body, even brain tissue."
With the new knowledge, the team setabout transitioning skin cells into dopamine neurons. During theprocess, timing was found to be key, and that bylowering the expression of p53 at the time in the cell cycle justbefore it prepared to duplicate, the transition was easily achieved.The team manipulated the cells at the right moment, turning on the aDNA modification enzyme known as Tet1, and dopamine neurons wereproduced.
Since production was completed, the researchers have tested the dopamine neurons, confirming that they're fully functional. The method is highly efficient and could, in the long term, allow for doctors to createpatient-specific neurons in the lab, before transplanting them intothe brain to repair the neurons damaged by Parkinson's disease.
"Our method is faster and much moreefficient than previously developed ones," says Feng. "The bestprevious method could take two weeks to produce 5 percent dopamineneurons. With ours, we got 60 percent dopamine neurons in 10 days."
The researchers published the findingsof the study in the journal Nature Communications.
Source: University at Buffalo