Characterization of olfactory stem cells.

ABSTRACT

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.