A team of University at Buffalo researchers has identified a key obstacle in the cell conversion process, the manipulation of which allows for much easier transitions between cell types. The breakthrough has big implications for the treatment of Parkinson's disease, with scientists able to create functional neurons to replace those damaged by the condition.
Parkinson's disease is a degenerative disorder that involves the loss of dopamine neurons in the brain, having a significant impact on the patient's motor skills. The new study has seen researchers attack the problem head on, attempting to find an efficient method of producing new dopamine neurons, which could then be transplanted into the patient's brain to help tackle the disease.
In the past, researchers have used embryonic stem cells for the purpose, but not only is the material difficult to obtain, but making dopamine neurons from stem cells is time-consuming and doesn't result in a large enough volume of cells. Researchers have also turned to normal cells, such as skin cells, for conversion but tested methods have suffered from similar issues, with too small a quantity of dopamine neurons being produced.
The new method takes a similar approach, but benefits from a significant breakthrough made by the Buffalo team. In essence, the researchers were able to identify a key obstacle to cellular conversion, which having been discovered can now be manipulated.
The team identified that a transcription factor protein, known as p53, guards against changes within a cell from one type to another, preventing any conversion. Once the expression of the protein was lowered, cell reprogramming became much more effective.
Cells have the same basic source code, with that code being read differently to generate all cell types in the body. Therefore, identifying p53 as the agent that maintains the status quo is significant to cell biology as a whole.
"It proves that we can treat the cell as a software system, when we remove barriers to change," says senior paper author Jian Feng. "We might be able able to play with the system more quickly and we might be able to generate tissues similar to those in the body, even brain tissue."
With the new knowledge, the team set about transitioning skin cells into dopamine neurons. During the process, timing was found to be key, and that by lowering the expression of p53 at the time in the cell cycle just before 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 were produced.
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 create patient-specific neurons in the lab, before transplanting them into the brain to repair the neurons damaged by Parkinson's disease.
"Our method is faster and much more efficient than previously developed ones," says Feng. "The best previous method could take two weeks to produce 5 percent dopamine neurons. With ours, we got 60 percent dopamine neurons in 10 days."
The researchers published the findings of the study in the journal Nature Communications.
Source: University at Buffalo
