By carefully harvesting tiny samples of olfactory cleft mucosal tissue and conducting single-cell analysis, a collaborative team led by University of Miami Miller School of Medicine researchers has found compelling evidence to support olfactory neurogenesis, the ability to regrow olfactory neurons to the brain.

“For decades, medical researchers have wondered whether or not neurogenesis was possible in adult humans,” said J. William Harbour, M.D., associate director for basic science at Sylvester Comprehensive Cancer Center, professor of ophthalmology, and vice chair for translational research and director of ocular oncology at Bascom Palmer Eye Institute. “This study uses cutting edge single-cell sequencing analysis to present compelling evidence that the answer is yes.”

Dr. Harbour, a member of the Interdisciplinary Stem Cell Institute, was a coauthor of the breakthrough study, “Single-Cell Analysis of Olfactory Neurogenesis and Differentiation in Adult Humans,” published February 17 in the journal Nature Neuroscience.  Miller School co-authors were Zoukaa B. Sargi, M.D., M.P.H., associate professor of clinical otolaryngology and neurosurgery; Sarah Kurtenbach, Ph.D., assistant scientist; Stefan Kurtenbach, Ph.D., assistant scientist; Garrett M. Goss, Ph.D., assistant scientist; Rhea Choi, M.D/Ph.D. student in the Medical Scientist Training Program (MSTP); and Michael A. Durante, M.D./Ph.D. student in the MSTP. Bradley J. Goldstein, M.D., Ph.D., formerly with the Miller School and now at Duke University Medical Center, was the corresponding author.

The study’s importance was emphasized by an accompanying “News & Views” column, “Neurogenesis Right Under Your Nose,” by three European researchers published in the same issue of Nature Neuroscience. “To our knowledge, no one has done a similar kind of analysis before,” they wrote, adding that the study “opens up new opportunities for investigating the role of olfaction directly in healthy individuals and people with various diseases.”

Dr. Harbour and his research team have studied the process by which stem cells in the eye produce differentiated offspring in laboratory models, including recent studies on retinoblastoma. This type of research can progress slowly due to the difficulty in obtaining the delicate tissue samples from human subjects.

In this study, the researchers were able to harvest tiny samples of olfactory epithelium – neurons that send signals regarding smells to the brain – from behind the nasal passages in seven patients ages 23 to 52 with benign tumors. “These cases provided access to normal olfactory tissue that required removal,” said Dr. Sargi. “Unlike the process for diagnostic biopsies, we needed to remove this delicate tissue and keep it intact for the research team. It took us many trials before we were able to adequately collect the samples.”

Using these freshly obtained samples, the researchers used single-cell RNA sequencing to analyze 28,726 cells. Dr. Stefan Kurtenbach said the team used a powerful analytical platform to analyze data from the individual cells. “We found that about 2 percent of those cells were neural stem cells, indicating that neuron production may continue into adulthood in humans,” added Durante.

Along with showing that neurons in the olfactory epithelium regenerate in adults, Dr. Sargi said the study provided new insights into the genes expressed by neurons as well as white blood cells involved in the local immune system in the olfactory tissue.

Looking ahead, the researchers believe the findings have important potential clinical implications. “This landmark paper confirms that single cell analysis is a critical new tool for understanding the complexity of stem cell biology in health and disease,” said Dr. Harbour.

“In the future, it may be possible to remove the stem cells, cultivate them in the laboratory and replant them in the olfactory epithelium,” said Dr. Kurtenbach. “This could be helpful to older people who lose their sense of smell.”

Durante added that loss of olfactory function is also associated with Alzheimer’s disease, Parkinson’s disease and other chronic conditions. “By applying these techniques, we may be able to learn more about this linkage,” he said. “It is certainly a fertile field for many types of clinical research.”