Converting Fibroblasts to Neurons
September 9, 2016
In the human body, there are cells and there are cell-ebrities. The billions of red blood cells carrying oxygen through the body are not allowed to have a nucleus and thus can’t reproduce for themselves. Keratinocyte skin cells’ only job is to create a protein that will turn it into a stiff, lifeless scale to be brushed off the skin millions of times per day.
The neuron, on the other hand, is a cell-ebrity. They survive for the entire lifespan of the human. The neurons in the brain and spinal cord call the shots for the whole body and the other neurons get to boss around everything from muscles to glands to whole organs.
New research from Duke University’s Pratt School of Engineering has provided a path to change zero cells into hero cells.
Biomedical engineering professor Charles Gersbach and graduate student Joshua Black have used a genetic engineering technique to convert connective tissue cells called fibroblasts into neurons. Their technique is the first to act directly on the DNA of one cell type to convert it into another cell type.
The human body contains more than 150 different types of cells with different sizes, shapes, growth patterns and jobs. With the exception of sperm and egg cells, they all have the same DNA.
The way that cells become those different types, simply, is that different genes get turned on as the cells develop from stem cells or as a mother cell divides into two daughters, sort of like different training.
The parietal cells of the stomach get demolitions training, and they equip themselves to secrete hydrochloric acid to break down our food. T-cells of the immune system get surveillance training, building receptors to recognize and destroy potential threats.
Neurons get the star treatment: management training and the ability to sing to each other and to other cells with electrical and chemical signals. They are shaped just right to receive and pass on that signaling song, and they have an entourage of glial cells to support them in everything they do.
Black and Gersbach used a genetic editing technique called CRISPR, which highlights certain specific DNA sequences, to turn on the genetic instructions for neurons in fibroblasts.
Fibroblasts are connective tissue cells that create the protein collagen. Collagen makes up the majority of our tendons and ligaments, as well as other dense and loose connective tissues all over the body. By turning on the genes responsible for training and creating neurons, the fibroblasts gained took on several characteristics of neurons. Gersbach said they began to take on the branched appearance of a neuron, express the same proteins as a neuron and even conduct electrical signals just like a neuron. Black and Gersbach gave the fibroblasts a shot at the big time.
Black and Gersbach were not the first to convert one cell type to another. Previous methods involved using viruses to inject multiple copies of the neuron instructions into a different cell type. With all of those extra copies floating around, even when the cell is working on being a fibroblast, it can’t help but move forward on the path toward becoming a neuron. It’s the American Idol scenario: an ordinary cell gets thrown into the bright lights of stardom and despite whoever the cell was before, it can’t help but become a star.
Black and Gersbach’s method is YouTube. The normal cell is given a new tool and by playing with the new tool, eventually he catches his cat playing the piano or records himself making funny faces with his baby. Instant stardom.
Doctors and researchers can use these fibroblasts-turned-neurons to run a number of tests and experiments for which using real neurons would be dangerous or impossible. Using these cells, doctors could test how medicines would interact with specific patients’ brain cells without any risk to the patient, or chart exactly how a disease affects human neurons without harming any humans.
“In the future, you could imagine implanting these types of cells as a therapy to treat diseases like Parkinson’s,” Gersbach said. But that will require significant additional research and demonstration of safety.”
Until then, though, the fibroblasts-turned-neurons get a chance to sing like stars.
Daniel Lane covers science, medicine, engineering and the environment in North Carolina.