After six years of hard work, Boston Children's Hospital (BCH) Harvard University Stem Cell Research Institute (HSCI) and Harvard University's Stem Cell and Regeneration Biology (HSCRB) researchers have finally successfully transformed mouse and human skin cells into pain nerves. Element, the neuron responds to a series of stimuli that cause acute and inflammatory pain. Related research was published in the recent issue of Natural Neuroscience.

Release date: 2014-11-27

After six years of hard work, Boston Children's Hospital (BCH) Harvard University Stem Cell Research Institute (HSCI) and Harvard University's Stem Cell and Regeneration Biology (HSCRB) researchers have finally successfully transformed mouse and human skin cells into pain nerves. Element, the neuron responds to a series of stimuli that cause acute and inflammatory pain. During these six years, scientists have experienced countless failures, and many times even made them feel that all these efforts are in vain.

This pain-receiving disease model in petri dishes will help deepen understanding of many different types of pain mechanisms, identify why different individuals respond differently to pain, and help improve the development of pain medications. Related research was published online in the November 24 issue of Nature Neuroscience.

Leading the study was Dr. Clifford Woolf, co-director of the HSCI Neurological Diseases Program. Woolf's collaborators include Professor Lee Rubin and Prof. Kevin Eggan of HSCRB. The neuropathic model created by Woolf and his team responds to two stimuli, one being a strong stimulus from physical injury and the other being inflammation or a mild stimulus from some form of cancer chemotherapy.

At the beginning of the project, Woolf's team tried to use embryonic stem cells to create pain neurons, but it turns out that this idea is far more challenging than imagined. Woolf said: "We spent three years trying to optimize the steps of the conversion process, but in the end it failed." Fortunately, their research is at the height of the development of stem cell biology and iPS technology. The iPS technology has the ability to transform adult cells into stem cells and then transform the stem cells into other types of adult cells.

The project was originally developed by HSCI researchers and pharmaceutical giant GlaxoSmithKline (GSK). Woolf said: "In the first three years, we have almost no results; but, like us, GSK also believes that this is a project that requires long-term efforts."

HSCI executive director Brock Reeve said the project is a good example of long-term collaboration between academia and industry, and that collaboration will be key to advancing basic scientific research and providing new approaches to drug discovery.

Woolf said: "We didn't make any progress at the beginning of the project, but we insisted on perseverance. Until we started trying to create pain neurons with mouse and human skin cells, many difficulties began to be solved. We got mature from mice. The pain neurons found a transcription factor that was not previously described. Subsequently, we successfully converted skin cells into pain neurons using five transcription factors (three of which were not previously described).

So, what prompted Woolf to persist in finding different ways to make painful neurons through embryonic stem cells after numerous failures? Woolf said: "This is really complicated because I actually have a lot of projects. But, I I always feel that we can try some new ways to advance our work. Whether these efforts are worthwhile, time will tell us the answer. I am an optimistic person. I think it is very important to create a pain neuron model for pain research. The failure of embryonic stem cell transformation has led us to the final selection of adult tissue samples, which makes the technique more clinically relevant, as it is easier to collect samples from patients suffering from different types of pain."

Source: biodiscover

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