Adult Olfactory Stem Cells Research Articles

Characterization of Olfactory Stem Cells

There is worldwide enthusiasm for the prospect of some kind of cellular transplant therapy for repair of failing organs. The olfactory mucosa of a patient's nose is easily biopsied to provide a ready source of multipotent cells. In this article we address practical issues pertinent to using olfactory neural stem cells for tissue repair. These cells are emerging as potentially most significant candidates for human tissue repair strategies. Previously we have shown that stem cells from olfactory mucosa are multipotent. As well, we have recently published three potential clinical applications. Their expression of dopaminergic markers in vitro and in a Parkinson's rat transplant model has been demonstrated. Their conversion to chondrogenic phenotype in vitro and in vivo has also been described, as has their transplant into a rat model of cardiac infarction. Here we examine in detail the biology of the olfactory neural stem cell using the rat as our animal model cell source. We establish its presence by examining self-renewal capacity and for phenotypic acquisition in inductive circumstances. We determine its frequency within the cell population and show that our culture system selects for this putative stem cell. Our studies demonstrate that adult olfactory stem cells, when transplanted into an environmental niche different from that of their origin, are able to demonstrate multipotency by acquiring the phenotype of the resident cells. We investigate how immediate the instruction need be. We test the hypothesis that olfactory neurospheres contain stem cells whose capacity for differentiation is triggered by signals of the immediate environmental niche. Significantly, of importance to any tissue regeneration endeavor, stem cell numbers were shown to be enriched by our culture methods. This was confirmed whether measured by sphere-forming capacity or differentiation response rate.

1039 Adult stem cells from persons with Parkinson's disease are therapeutic in a rat model

Background: Parkinson's disease is a complex disorder the many symptoms of which are due to degeneration of dopaminergic neurons in the substantia nigra that project into the caudate-putamen. The research reported here was modelled on a recent report of the efficacy of embryonic stem cells in ameliorating the effects of 6OH-dopamine lesion in a mouse model of Parkinsons disease (Bjorklund et al, 2002). Methods: Olfactory adult stem cell (OSC) cultures were established from biopsies of olfactory mucosa of PD and normal human patients, obtained under local anaesthetic (Murrell et al, 2005). These stem cells were differentiated in vitro and as well transplanted as stem cells into the caudate putamen of 6OH-dopamine lesioned rats. Results: Olfactory stem cells were able to be induced in vitro to express tyrosine hydroxylase. Nine severely lesioned rats were chosen for follow up. Three were transplanted with vehicle only, three were transplanted with OSCs from normal human and three were transplanted with PD OSCs. All six transplanted animals displayed marked reduction of symptoms over a three month period whilst shams remained rapid turners. Transplanted animals contained human derived cells that expressed both TH and dopamine transporter. Conclusion: These results strongly support the potential use of autologous human adult olfactory stem cells as a means of nerve regeneration treatment of Parkinson's and other neurodegenerative disorders. Bjorklund LM, Sanchez-Pernaute R, Chung S, Andersson T, Chen IY, McNaught KS, Brownell AL, Jenkins BG, Wahlestedt C, Kim KS, Isacson O. (2002) Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model. Proc Natl Acad Sci U S A. 99:2344-9. Wayne Murrell, Fran篩s F鲯n, Andrew Wetzig, Nick Cameron, Karisha Splatt, Bernadette Bellette, John Bianco, Chris Perry, Gabriel Lee, and Alan Mackay-Sim (2005) Multipotent stem cell in adult olfactory mucosa Developmental Dynamics 233:496-515.