Melanocytes without intermediaries
The new technique directly transforms fibroblasts into melanocytes
LifeSciencesToday based on the materials of the University of Pennsylvania:
Cutting Out the Cellular Middleman: New Technology Directly Reprograms Skin Fibroblasts For a New RoleThe main component of connective tissue – fibroblasts – is the most common type of cells in our body.
Scientists from the Perelman School of Medicine of the University of Pennsylvania, The Wistar Institute, The Boston University School of Medicine and the New Jersey Institute of Technology have found a way to reprogram fibroblasts into functional melanocytes – cells, synthesizing the pigment melanin. The new technique will have a major impact on the development of cellular treatments for skin diseases such as vitiligo, as well as new screening strategies for melanoma. The study was published in the journal Nature Communications (Yang et al., Direct conversion of mouse and human fibroblasts to functional melanocytes by defined factors).
The new technique eliminates the use of intermediary cells. "Thanks to direct reprogramming, we do not need to go through the stage of pluripotent stem cells. We transform fibroblasts directly into melanocytes. Therefore, these cells do not have oncogenicity," explains senior author of the study Xiaowei Xu, MD, PhD, associate professor of Pathology and Laboratory Medicine.
Reprogramming cells of one type into cells of another can hardly be called something unusual. Nature does this all the time, especially when cells divide and differentiate during the development of the embryo into an adult organism. Medicine studies how to use cellular specialization to develop new clinical treatments. However, controlling this process is a difficult task. It is difficult to determine the specific transcription factors needed to create the right type of cells. In addition, the process of reprogramming a cell first into an induced pluripotent stem cell (IPSC) capable of differentiation, and then into a cell of the desired type is fraught with the formation of tumors.
Dr. Xu and his colleagues began by searching for specific transcription factors important for melanocyte formation in the literature. After screening the 10 factors found, they identified three necessary for the formation of melanocytes: Sox10, MITF, and PAX3 – a combination called SMP3.
"We have done a huge amount of work," says Dr. Xu – yi, removing all combinations of other transcription factors, we found that these three are of crucial importance."
The researchers first tested the SMP3 combination on mouse embryonic fibroblasts, which quickly began to express melanocyte markers.
The next step was to use a combination of SMP3 on human embryonic dermal cells, which also led to the rapid formation of melanocytes (human-induced melanocytes, hiMels). Further testing confirmed that the obtained hiMels really function as normal melanocytes not only in cell culture, but also in the body of animals, successfully synthesizing the pigment melanin. Functionally, these cells turned out to be identical in all respects to normal melanocytes.
Dr. Xu and his colleagues hope to use their new technique in the treatment of a wide range of skin diseases, especially such as vitiligo, for which cell therapy is the most effective approach.
In addition, this technique may become a new way to study melanoma. By obtaining melanocytes from fibroblasts of melanoma patients, Dr. Xu explains, "we can conduct screening not only to find out why these patients are predisposed to the development of melanoma, but also, possibly, to search for low-molecular compounds that can prevent the development of a tumor."
Perhaps most importantly, the researchers say, there are many more readily available fibroblasts in the body than tissue-specific adult stem cells, which allows the new technique to be used to develop other cellular therapies.
Portal "Eternal youth" http://vechnayamolodost.ru26.12.2014