Human Skin Cells Successfully Converted into Motor Neurons

Human Skin Cells Successfully Converted into Motor Neurons

Scientists have discovered how adult skin cells can be converted into motor neurons without transitioning them through a stem cell state.

The findings promise to help researchers better understand motor neuron diseases, such as amyotrophic lateral sclerosis (ALS).

The study, “MicroRNAs Induce a Permissive Chromatin Environment that Enables Neuronal Subtype-Specific Reprogramming of Adult Human Fibroblasts,” was published in the Cell Stem Cell journal.

Growing motor neurons — the nerve cells damaged in ALS — from easily obtained cells is a promising approach to treating motor neuron diseases. But the process has been hampered by scientists’ lack of understanding of all the molecular players that regulate the process.

Researchers at the Washington University School of Medicine in St. Louis have identified four molecular players that allow skin cells to convert themselves into motor neurons.

Prior studies had used differentiated cells — those with an assigned function — to make a new cell type. But first cells needed to enter a stem cell state, creating so-called induced pluripotent stem cells, or iPS. Under the right conditions, iPS could be reprogrammed into any cell type.

The process the Washington University researchers use does not require skin cells to enter the iPS stage. Instead, they’re directly converted into motor neurons. This has many advantages, including overcoming ethical issues, since this pluripotent state is similar to embryonic stem cells.

Also, by skipping the stem cell step, the motor neurons retain the age of the skin cells, and consequently of the donor. For research purposes, cell age is an important factor when researchers are studying neurodegenerative diseases that develop at different stages of life.

“In this study, we only used skin cells from healthy adults ranging in age from early 20s to late 60s,” study lead author Andrew S. Yoo, an assistant professor of developmental biology, said in a press release. “Going back through a pluripotent stem cell phase is a bit like demolishing a house and building a new one from the ground up. What we’re doing is more like renovation. We change the interior but leave the original structure, which retains the characteristics of the aging adult neurons that we want to study.”

Building on the team’s previous findings, the researchers exposed skin cells to two small RNA molecules, called microRNAs, which they knew were highly enriched in the brain. MicroRNA-9 and microRNA-124 were important for converting skin to motor neurons but the process remained incomplete.

After trying a number of combinations, researchers found that adding two transcription factors – ISL1 and LHX3 – to the mix led to the skin cells being converted into spinal cord motor neurons. The process required 30 days.

Combining microRNA-9 and microRNA-124 with ISL1 and LHX3 remodels the cells’ genetic material, folding up the genetic material for making skin, and unfolding the instructions for making motor neurons.

The team said the newly converted neurons shared characteristics of normal mouse motor neurons, but further studies are needed to assess whether the converted neurons are perfect matches for human motor neurons.

“Our research revealed how small RNA molecules can work with other cell signals called transcription factors to generate specific types of neurons, in this case motor neurons. In the future, we would like to study skin cells from patients with disorders of motor neurons. Our conversion process should model late-onset aspects of the disease using neurons derived from patients with the condition,” Yoo concluded.

11 comments

    • Charlie says:

      Karen, nothing is coming out of the labs which helps us now. After 20 years we have only Riluzole and Radicava. The first gives some pALS an extra two months, and the latter gives some wealthy pALS and extra year.
      Research is completely ‘scatter-gun’ and researchers constantly find interesting things about cells of all types but they simply have no idea if what they are finding is a cause or a symptom.

    • Cynthia Dixon says:

      Read up on Brainstorm cell Therapeutics. They are here now in the USA. I believe they will have six locations for clinical trials that are in the third phase. They are showing good results and I am on their newsletter list and receive information almost every week. I would get in touch with them. Keep believing. No matter what disease people have, if you look up people who have successfully made it through – – most of them kept believing.

  1. Charlie says:

    This is an interesting development but it poses more questions than answers.
    Can the skin cells which have undergone this Damascene Conversion to Motor Neurons replace ones killed in ALS patients?
    Can they then reverse the effects of ALS in a kind-of ‘new engine for the body’s motor’ ?
    Are they a ‘one-for-one’ refit ?
    I expect we might find out in, say, a year or two’s time. A clue to whether this ‘observation’ has future mileage is whether the research community take up the next stage quickly or drop it like a hot potato.

  2. Charlie says:

    Note the date:
    Los Angeles – Oct. 25, 2013 – Although the technology has existed for just a few years, scientists increasingly use “disease in a dish” models to study genetic, molecular and cellular defects. But a team of doctors and scientists led by researchers at the Cedars-Sinai Regenerative Medicine Institute went further in a study of Lou Gehrig’s disease, a fatal disorder that attacks muscle-controlling nerve cells in the brain and spinal cord.

    After using an innovative stem cell technique to create neurons in a lab dish from skin scrapings of patients who have the disorder, the researchers inserted molecules made of small stretches of genetic material, blocking the damaging effects of a defective gene and, in the process, providing “proof of concept” for a new therapeutic strategy – an important step in moving research findings into clinical trials.

    The study, published Oct. 23 in Science Translational Medicine, is believed to be one of the first in which a specific form of Lou Gehrig’s disease, or amyotrophic lateral sclerosis, was replicated in a dish, analyzed and “treated,” suggesting a potential future therapy all in a single study.

  3. Charlie says:

    From the same article in 2013:
    “Svendsen recently received a $17.8 million grant from the California Institute for Regenerative Medicine. In collaboration with Baloh and the ALS clinical team at Cedars-Sinai, this study will support a novel stem cell and growth factor therapy for ALS.”

    He’s a real smart cookie of a researcher and receives a regular truckload delivery of funding dollars.

  4. Cynthia Dixon says:

    Thank God there is so much out there they are exploring!!. I still remain hopeful –that’s all we can do !! Im following Brainstorm… they are in the 3 rd phase here in United States with clinical trials. They are reporting great results. Also there is Tirasemtiv – just finished its 3rd phase- also showing good results . Keep fighting… we are warriors through this!!

  5. Michelle Kafafi says:

    Copper-Atsm is the most important breakthrough to date. It actually reverses the disease. But has only bee used in mice. Until then try organic diet, heavy supplements and meditation. Since we are all energy forgive and get on. Listen to Gaia.

  6. TomB says:

    Unless a braketrough is done in improving the clinical descriptions/classifications of MND/ALS subtypes and combining them with better targetted molecular studies, the search for solution is to random. This requires a lot of work to improve the quality of clinical data and a lot of dialog between doctors and molecular biologists. Not necessarily easy. But I cross my fingers and believe that something like Flemming’s discovery of peniciline may happen soon.

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