A Drug Cocktail Can Reprogram Skin Cells Into Heart And Brain Cells

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In a major breakthrough, new research has demonstrated a combination of chemicals can morph humble skin cells into neurons or heart cells

Stem cells can be turned into virtually any cell you desire, but imagine if you could turn cells straight into another type without using them at all? That’s what cellular reprogramming potentially offers – a fast track transformation process. Now, two studies from the Gladstone Institute have shown that a unique combination of chemicals can cause skin cells to become brain or heart varieties, without having to apply any genes.

“This method brings us closer to being able to generate new cells at the site of injury in patients. Our hope is to one day treat diseases like heart failure or Parkinson’s disease with drugs that help the heart and brain regenerate damaged areas from their own existing tissue cells. This process is much closer to the natural regeneration that happens in animals like newts and salamanders, which has long fascinated us” 

Repairing the heart

Adults don’t regenerate cardiac tissue very well, and efforts with stem cells so far have had difficulty integrating new stem cells into the heart. It’s already been demonstrated that applying specific genes to scar tissue cells in the heart can coax them into becoming muscle again, but genes are tricky to deliver and this new work hints that chemicals might do the same job. In one of the studies published in Science, through trial and error 9 chemicals were identified that could effectively shift skin cells into heart ones. A first batch returns the cell into an intermediate, stem cell like state, and a second triggers them to become new heart muscle cells. The method was so effective that 97% of the cells targeted actually started beating, resembling healthy heart muscle. They also carried on working when they were implanted into a mouse heart. 

Neural stem cells born from skin cells Credit: Mingliang Zhang, PhD, Gladstone Institutes

…and the brain

In the second groundbreaking study, the scientists created neural stem cells from skin using 9 chemicals again. The new chemical cocktail encompassed some of the same molecules, but included some different ones too. Over 10 days, the skin cells were gradually reprogrammed until their old genes were inactivated and genes matching a neural stem cell identity were turned on. When these were again transplanted into a mouse brain, these cells could replicate and were able to develop into the 3 types of brain cell: neurons, oligodendrocytes, and astrocytes. 

“With their improved safety, these neural stem cells could one day be used for cell replacement therapy in neurodegenerative diseases like Parkinson’s disease and Alzheimer’s disease. In the future, we could even imagine treating patients with a drug cocktail that acts on the brain or spinal cord, rejuvenating cells in the brain in real time”

This work is really exciting, but delivering a similar cocktail of drugs to a very specific location without triggering neighbouring cells to change too would be a big challenge. 

Read more at MedicalXpress