Nociceptive neurons from fibroblasts
Pain in the Petri dish
NanoNewsNet based on HSCI materials: Pain in a dishHuman Sensory Neurons Sensitive to Pain Stimuli,
obtained by transformation of skin cells using a set of five genes.
This in vitro model can facilitate the study of various types of pain.
(Photo: Liz Buttermore)
Scientists at the Harvard Stem Cell Institute (HSCI), in collaboration with colleagues from the Department of Stem Cells and Regenerative Biology at Harvard University, transformed mouse and human skin cells (fibroblasts) into pain-sensitive neurons that respond to a number of stimuli that cause acute and inflammatory pain. It took scientists six years of hard work to achieve this success.
This in vitro model of pain perception can deepen the understanding of its various types, explain why people react differently to pain and why their risk of developing chronic pain is also different, and also make it possible to develop more effective painkillers. An article about the work (Wainger et al., Modeling pain in vitro using nociceptor neurons reprogrammed from fibroblasts) is published in the journal Nature Neuroscience.
Pain-sensitive (nociceptive) neurons, obtained by Clifford Woolf, MD, PhD, and his group, respond to both types of intense stimuli and to weaker stimuli associated with inflammation. The response of neurons to all types of pain stimuli confirms that they function in the same way as created by nature itself, emphasizes Dr. Wolf.
At the beginning of the project, Dr. Wolf and his colleagues tried to create pain-sensitivity neurons from embryonic stem cells, but the task turned out to be much more difficult than scientists had expected.
"We spent three years trying to reproduce the stages of development, and it ended in complete failure," recalls Dr. Wolf.
But their attempt to get pain–sensitive neurons came at a very important stage in the development of stem cell biology, coinciding with the development of methods for creating induced pluripotent stem cells - the emergence of the possibility of transforming human somatic cells first into stem cells, and then into other types of somatic cells. Working with mouse and human skin cells put everything in its place.
"We took mature mouse pain neurons and found transcription factors that had not been described in them before," Wolfe continues.
Then, using a total of five factors, including three not previously described, the researchers directly transformed fibroblasts into neurons of the desired type.
"I think the ability to receive human pain-sensitive neurons is very important for studying it. In addition, our failure with embryonic stem cells led us to work with adult tissue samples, which makes this method much more clinically significant, since they are easy to take from patients suffering from various types of pain," comments Wolf, professor of neurology and neurobiology at Harvard Medical School.
The pain-sensitive neurons developed by his group, the scientist emphasizes, "perfectly simulate" neuropathies and hypersensitivity to pain observed in some of the patients who donated their skin cells to scientists. "Many pain conditions are caused by genetic mutations, and now we can model them."
Portal "Eternal youth" http://vechnayamolodost.ru23.12.2014