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A team of researchers from the Tufts University School of Medicine has developed a method for culturing and maintaining olfactory stem cells, which can then be used to restore tissue in the nose. This discovery suggests that future therapies could be developed to restore the sense of smell in individuals injured by injury or degeneration.
Stem cells, called horizontal basal cells (HBCs), can repopulate all types of olfactory epithelial (EO) cells, including sensory neurons, when they are transplanted into an injured tissue. Posted today in the journal Stem Cell Reports, the development paves the way for new research on stem cell transplant therapies or pharmacological approaches that stimulate the regeneration of tissues by stem cells located in the nose.
Nerves that transmit smell are unique to the rest of the nervous system in that they can trigger a robust and almost complete regenerative response after injury. EO tissues contain two types of stem cells: globular basal cells and CBHs. GBCs have been successfully cultured and appear to play a key role in the repopulation of lost cells in favor of systematic renewal. However, CBH remains dormant and is activated only after an injury. Unfortunately, studies on these cells have been limited by the fact that they could not be expanded and maintained in culture. In this study, researchers determined the optimal conditions for the expansion and maintenance of healthy CBH stem cells in culture, the borrowing methods, and the factors used to maintain respiratory stem cells.
"Once we determined that we could grow HBCs in the lab and that they were expressing the same molecular identification markers found in vivo, we sought to confirm if they would work as well as the CBH in vivo, can they regenerate the tissues that have been treated? " hurt – and they did it! said Dr. James Schwob, Ph.D., professor of molecular and chemical developmental biology at the Tufts University School of Medicine and corresponding author of the study.
Despite a natural capacity for regeneration, malfunctions of smell are still reported in 19.4% of the population (OLFACAT study, 2003), of which 0.3% in total loss of odor. The causes range from aging, trauma, smoking and neurodegenerative diseases to certain drugs.
Schwob and his team found that laboratory-developed HBCs were able to treat olfactory lesions, generating several types of cells, including Sus cells, basal cells and olfactory sensory neurons.
"The CBHs in culture remained at rest, practically in vivo, but we were able to activate them in an active state to start the differentiation process into various olfactory epithelial cells just before grafting them into an injured tissue," said Jesse Peterson . , Ph.D., first author of the study and currently a postdoctoral fellow at the Laboratory of Molecular Biology of the MRC. Peterson conducted this study as part of his doctoral dissertation at the Sackler School of Graduate Biomedical Sciences in Tufts, advised by Schwob.
The trigger used was retinoic acid, which has the effect of lowering the levels of P63 protein in cells, which leads to the activation of stem cells. P63 functions as a "master control switch" and is known to decrease levels during injury, causing CBHs to go dormant to in vivo activation. A deeper understanding of the role of P63 has been hampered by slow in vivo studies. With HBCs developed in the laboratory, activation mechanisms can be examined more closely.
"Now that we can create a dormant stem cell pool, we see this as a useful tool for exploring ways to guide cell differentiation according to specific cell types and to develop new stem cell-based therapies for regeneration. Tissue and sensory – using the patient's own stem, cells for culture and transplantation, or pharmacological interventions to activate the patient's own dormant stem cells in the nose, "said Schwob.
Other authors who contributed to this study are Brian Lin, Ph.D., Camila Barrios-Camacho, Daniel Herrick, MD, Ph.D., and Julie Coleman, Ph.D., all graduates or students of Tufts, Woochan Jang, Ph.D.D, a former Research Assistant Professor at Tufts, and Eric Holbrook, MD, Mbadachusetts Eye and Ear, and Harvard Medical School.
This work was funded by awards from the National Institute of Deafness and Other Communication Disorders of the National Institutes of Health National Institutes of Health (R01DC002167, F31DC014637, F30DC013962). , F31DC014398). This content only engages the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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