Stem Cells, Vol. 18, No. 4, 295-300, July 2000

Isolation and Characterization of Neural Stem Cells from the Adult Human Olfactory Bulb
Stefano F. Paganoa, Francesco Impagnatiellob,

We have recently isolated stem cells deriving from the olfactory bulbs of adult patients undergoing particularly invasive neurosurgery. After improving our experimental conditions, we have now obtained neural stem cells according to clonal analysis. The cells can be expanded, established in continuous cell lines and differentiated into the three classical neuronal phenotypes (neurons, astrocytes, and oligodendrocytes). Also, after exposition to leukemia inhibitory factor, we are able to improve the number of neurons, an ideal biological source for transplantation in various neurodegenerative disorders.

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DISCUSSION

Pharmacological or neurosurgical therapies are currently used to treat neurological damages in various neurodegenerative disorders (i.e. Parkinson's disease, Alzheimer's disease, Huntington's disease, etc.), but all these strategies are not efficient in preventing or reverting these progressive neurodegenerative processes. Recently, a new approach has been introduced—the cell therapy [20]. This approach is based on the transplantation of appropriate cells, which must not only be well characterized and biologically and immunologically safe, but also sufficiently numerous to ensure adequate post-transplantation survival, tissue regeneration, and an acceptable degree of functional recovery and/or symptomatic improvement.

For the first time we have successfully isolated neural stem cells from the olfactory bulb of adult human subjects. The isolation and characterization of neural stem cells from the human olfactory bulb open up a further interesting therapeutic perspective.

The high regenerative potential of this area suggests that the olfactory bulb is an ideal autologous source for neurodegenerative disease. Under our optimized conditions, the stem cells obtained from the olfactory bulb, like embryonic stem cells, proliferate and are capable of differentiating into the three classical neural phenotypes. We suggest that stem cells deriving from this area can be simply explanted by means of partial bulbectomy in patients (with few damaging effects such as anosmia).

As a result of our many years of experience in manipulating neural stem cells, we are able to expand these cells considerably and, by means of the addition of LIF, ensure their differentiation into neurons [16], the elective biological source for autotransplantation in various neurodegenerative disorders. In particular, the discovery of a large number of immunoreactive tyrosine hydroxylase structures in the olfactory bulbs and peduncles of elderly humans [21] suggests that the olfactory bulb is a hypothetical source for the autotransplantation therapy in Parkinson's disease.

In support of the idea of using olfactory bulb neural stem cells for autologous transplantation in patients with Parkinson's disease, we have recently used an experimental model of Parkinson's disease. Lesions in the nigrostriatal zone were induced by inoculation of 6-hidroxy-dopamine in CD1 mice, and we investigated the ability of these cells to elicit functional recovery after intrastriatal transplantation. These data [22, 23] show that inoculation of these cells induces functional recovery in comparison with control untransplanted mice, and detailed biochemical and immunohistochemical evaluations are currently under way. These are fundamental confirmatory data for the future use of these cells for transplant therapy in patients with Parkinson's disease and other neurodegenerative disorders.