Study Demonstrates Potency of Adult Olfactory Stem Cells After Transplantation
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BOSTON — Unlike many other biological systems, the olfactory (smell) system contains stem cells that, throughout life, can replace a variety of cell types following injury. These “multipotent” cells may eventually have therapeutic applications. Advancing this pursuit, researchers at Tufts University School of Medicine (TUSM) have devised and tested a novel culture system that closely resembles the structure of living tissue. In the November 2008 issue of Experimental Neurology, they report on their successful in vivo transplantation of olfactory cells maintained in this three-dimensional culture system.
“It appears as if globose basal cells (GBCs), horizontal basal cells (HBCs), and duct/gland cells of the olfactory epithelium all have some capacity for multipotency after being cultured, as long as the cells maintain the kinds of complex interactions among themselves that characterize the tissue itself. When we maintained a mixture of these cell types from methyl-bromide exposed olfactory epithelium in air-liquid cultures with a feeder layer for 11 days, we observed the formation of spheres, and these spheres were essential for successful transplantation into the regenerating olfactory epithelium of methyl-bromide exposed mice,” states principal investigator James E. Schwob, MD, PhD, Bates professor of anatomy and cellular biology at Tufts University School of Medicine and faculty member of the cell, molecular, and developmental biology, and neuroscience programs at the Sackler School of Graduate Biomedical Sciences at Tufts.
“Methyl bromide exposure induces a cellular response to injury, which proved to be necessary for sphere formation. Spheres did not form when we used primarily neurogenic cells, such as those harvested from either normal olfactory epithelium or from the epithelium of mice from which the olfactory bulb – the brain’s center for smell – had been removed,” says Schwob.
While the majority of previous studies have used embryonic or neonatal cells, the Tufts researchers used a three-dimensional culture system with adult olfactory epithelium, which will be the most likely tissue source for therapeutic use of these stem cells.
“This three-dimensional culture system represents a substantial advance on previous means of culturing peripheral olfactory cells,” Schwob says. “Similar cells maintained in a two-dimensional submerged monolayer culture failed to incorporate into regenerating tissue, indicating a loss of potency. We did not appreciate the significant difference between the two types of culture systems until the transplantation stage because, in culture, both systems effectively gave rise to multiple cell types, including neurons and various types of non-neuronal cells.”
Schwob and colleagues report that they are working on refining this culture system, and have yet to identify the specific factors that are permitting the cells in culture to retain morphological and functional features characteristic of cells in living organisms. Further investigation will likely provide better understanding of future therapeutic use of olfactory epithelium-derived stem and progenitor cells.
First author Woo chan Jang, PhD, is a research assistant professor in the department of anatomy and cellular biology and former senior research associate in Schwob’s laboratory. Schwob is also the chair of the department of anatomy and cellular biology at Tufts University School of Medicine.
This work was supported by grants from the National Institutes of Health, the Ellison Foundation, and a core grant to the Tufts Center for Neuroscience Research.
Jang W, Lambropoulos J, Woo JK, Peluso CE, Schwob JE. Experimental Neurology. 2008. (November); 214(1): 25-36. “Maintaining Epitheliopoietic Potency When Culturing Olfactory Progenitors.”
About Tufts University School of Medicine and the Sackler School of Graduate Biomedical Sciences
Tufts University School of Medicine and the Sackler School of Graduate Biomedical Sciences at Tufts University are international leaders in innovative medical education and advanced research. The School of Medicine and the Sackler School are renowned for excellence in education in general medicine, special combined degree programs in business, health management, public health, bioengineering and international relations, as well as basic and clinical research at the cellular and molecular level. Ranked among the top in the nation, the School of Medicine is affiliated with six major teaching hospitals and more than 30 health care facilities. The Sackler School undertakes research that is consistently rated among the highest in the nation for its effect on the advancement of medical science.