Pluripotent Adult Stem Cell from Olfactory Mucosa

Alan Mackay-Sim

National Centre for Adult Stem Cell Research, Griffith University, Australia

Abstract

Neurogenesis continues throughout adult life in the olfactory mucosa, the organ of smell in the nose. The stem cells in this tissue normally make sensory neurons and non-neural cells. We investigated the developmental potency of mouse olfactory stem cells by transplanting them into the blastocyst. The resulting embryos and live young were chimearic, composed in part of donor cells carrying the EGFP transgene. Offspring of chimearic mice also carried the EGFP transgene, demonstrating germline chimaerism and hence pluripotency. These olfactory stem cells failed to make teratomas in immune-compromised mice. This is the first evidence for an adult stem cell that is pluripotent and the first evidence for a pluripotent cell that is not teratogenic. Olfactory stem cells are accessible in humans via biopsy through the nose. We have established a bank of 200 olfactory stem cell lines from humans with different neurological conditions to use as stem cell models of neurological disease. Initial analysis of 42 olfactory stem cell lines compared cells from people with schizophrenia, Parkinson’s disease or healthy controls. Using gene and protein expression profiling and functional assays we found that olfactory stem cells show disease-specific differences in gene and protein expression and in functions consistent with alterations in post-mortem brain samples from patients. Bioinformatic analyses identified neurodevelopmental pathways altered in schizophrenia and metabolic and mitochondrial pathways altered in Parkinson’s disease, consistent with hypotheses about their aetiologies. Our results demonstrate a potential source of autologous adult stem cells for transplantation and for stem cell models of disease.