Abstract
We investigated whether human cord blood-selected CD133+ stem cells (HSC) may engraft the olfactory mucosa and contribute to restoration of neuro-olfactory epithelium (NE) in nod-scid mice damaged by dichlobenil. The herbicide dichlobenil selectively causes necrosis of the dorsomedial part of the NE and underlying mucosa, while the lateral part of the olfactory region remains undamaged. The aim of this research was to demonstrate that HSC stimulate self-renewal of neuronal stem cells and promote their differentiation into bipolar olfactory neurons to replace the injured NE. By PCR, we tested the presence of three human-specific microsatellites (CODIS; Combined DNS Index System), used as DNA markers for traceability of the engrafted cells, demonstrating their presence in various tissues of the host, including the olfactory mucosa, 1 month after transplantation. By immunohistochemistry and lectin staining, we demonstrated that, in injured mice, HSC contributed to stimulating residual endogenous olfactory neurons, promoting recovery of the original phenotype of the NE, in contrast to the lack of spontaneous regeneration in similar injured areas always seen in the nontransplanted control mice. Multiple colour fluorescence in situ hybridisation (M-FISH) analysis detected seven human genomic sequences present in different chromosomes and provided further evidence of positive prolonged engraftment of chimeric cells in the olfactory mucosa. This study provides the first evidence that transplanted HSC migrating to the neuro-olfactory mucosa may contribute to NE structure restoration with resumption of the sensorineural olfactory loss.
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References
Farbman AI. Cell biology of olfaction. Cambridge University Press, Cambridge, 1992.
Ding XX, Coon MJ. Purification and characterization of two unique forms of cytochrome P 450 from rabbit nasal microsomes. Biochemistry 1988;27:8330–7.
Chen Y, Getchell ML, Ding X, et al. Immunolocalization of two cytochrome P450 isozymes in rat nasal chemosensory tissue. Neuroreport 1992;3:749–52.
Suzuki Y, Schafer J, Farbman AI. Phagocytic cells in the rat olfactory epithelium after bulbectomy. Exp Neurol 1995;136:225–33.
Suzuki Y, Takeda M, Farbman AI. Supporting cells as phagocytes in the olfactory epithelium after bulbectomy. J Comp Neurol 1996;376:509–17.
Huard JM, Schwob JE. Cell cycle of globose basal cells in rat olfactory epithelium. Dev Dyn 1995;203:17–26.
Calderon-Garciduenas L, Rodriguez-Alcaraz A, Villarreal-Calderon A, et al. Nasal epithelium as a sentinel for airborne environmental pollution. Toxicol Sci 1998;46:352–64.
Graziadei, PPC, Monti Graziadei GA. Continuous nerve cell renewal in the olfactory system. In: Jacobson M, editor. Handbook of sensory physiology. Vol. 9 Development of sensory systems. Springer, New York, 1978:55–83.
Farbman AI. Olfactory neurogenesis: genetic or environmental controls? Trends Neurosci 1990;13:362–5.
Beyers DW, Farmer MS. Effects of copper on olfaction of Colorado pikeminnow. Environ Toxicol Chem 2001;20:907–12.
Baldwin DH, Sandhal JF, Labenia JS, et al. Sublethal effect of copper on coho salmon: impacts on nonoverlapping receptor pathways in the peripheral olfactory nervous system. Environ Toxicol Chem 2003;22:2266–74.
Schwob JE, Youngentob SL, Mezza RC. Reconstitution of the rat olfactory epithelium after methyl bromide-induced lesion. J Comp Neurol 1995;359:15–37.
Bergman U, Brittebo EB. Methimazole toxicity in rodents: covalent binding in the olfactory mucosa and detection of glial fibrillary acidic protein in the olfactory bulb. Toxicol Appl Pharmacol 1999;155:190–200.
Brandt I, Brittebo EB, Feil VJ, et al. Irreversible binding and toxicity of the herbicide dichlorobenil (2,6-dichlorobenzonitrile) in the olfactory mucosa of mice. Toxicol Appl Pharmacol 1990;103:491–501.
Bergman U, Ostergren A, Gustafson A-L, et al. Differential effects of olfactory toxicants on olfactory regeneration. Arch Toxicol 2002;76:104–12.
Buckland ME, Cunningham AM. Alterations in expression of the neurotrophic factors glial cell line-derived neurotrophic factor, ciliary neurotrophic factor and brain-derived neurotrophicfactor, in the target-deprived olfactory neuroepithelium. Neuroscience 1999;90:333–47.
Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999;284:143–7.
Strem BM, Hicok KC, Zhu M, et al. Multipotential differentiation of adipose tissue-derived stem cells. Keio J Med 2005;54:132–41.
Mizuno H, Zuk PA, Zhu M, et al. Myogenic differentiation by human processed lipoaspirate cells. Plast Reconstr Surg 2002;109:199–209.
Van Damme EJM, Peumans WJ, Pusztai A, et al. Handbook of plant lectins: properties and biomedical applications. Wiley, Chichester, England, 1998.
Ricci U, Sani I, Guarducci S, et al. Infrared fluorescent automated detection of thirteen short tandem repeat polymorphisms and one gender-determining system of the CODIS core system. Electrophoresis 2000;213:564–70.
Taniguchi K, Saito H, Okamura M, et al. Immunohistochemical demonstration of protein gene product 9.5 (PGP 9.5) in the primary olfactory system of the rat. Neurosci Lett 1993;156:24–6.
Johnson EW, Eller PM, Jafek BW. Protein gene product 9.5 in the developing and mature rat vomeronasal organ. Dev Brain Res 1994;78:259–64.
Schofield JN, Day INM, Thompson RJ, et al. PGP 9.5, a ubiquitin C-terminal hydrolase; pattern of mRNA and protein expression during neural development in the mouse. Dev Brain Res 1995;85:229–38.
Key B, Akeson RA. Olfactory neurons express a unique glycosylated form of the neural cell adhesion molecule NCAM. J Cell Biol 1990;110:1729–43.
Key B, Akeson RA. Immunochemical markers for the frog olfactory neuroepithelium. Dev Brain Res 1990;57:103–17.
Breer H. Molecular reaction cascade in olfactory signal transduction. J Steroid Biochem Mol Biol 1991;39:621–5.
Franceschini V, Lazzari M, Revoltella RP, et al. Histochemical study by lectin binding of surface glycoconjugates in the developing olfactory system of rat. Int J Dev Neurosci 1994;12:197–206.
Lipscomb BW, Treolar HB, Klehoff J, et al. Cell surface carbohydrates and glomerular targeting of olfactory sensory neuron axons in the mouse. J Comp Neurol 2003;467:22–31.
Henion TR, Raitcheva D, Grosholz R, et al. β1,3-N-Acetylglucosaminyltransferase 1 glycosilation is required for axon pathfinding by olfactory sensory neurons. J Neurosci 2005;25:1894–903.
St. John J, Key B. A model for axonal navigation based on glycocodes in the primary olfactory system. Chem Senses 2005;30 Suppl 1:i123–4.
Hao HN, Zhao J, Thomas RL, et al. Fetal human hemopoietic stem cells can differentiate sequentially into neural stem cells and then astrocytes in vitro. J Hematother Stem Cell Res 2003;12:23–32.
Baal N, Reisinger K, Jahr H, et al. Expression of transcription factor Oct-4 and other embryonic genes in CD133 positive cells from human umbilical cord blood. Thromb Haemost 2004;92:767–75.
Nan B, Getchell ML, Partin JV, et al. Leukemia inhibitory factor, interleukin-6, and their receptors are expressed transiently in the olfactory mucosa after target ablation. J Comp Neurol 2001;435:60–77.
Getchell TV, Shah DS, Partin JV, et al. Leukemia inhibitory factor mRNA expression is upregulated in macrophages and olfactory receptor neurons after target ablation. J Neurosci Res 2002;67:246–54.
Getchell TV, Subhedar NK, Shah DS, et al. Chemokine regulation of macrophage recruitment into the olfactory epithelium following target ablation: involvement of macrophage inflammatory protein-1 and monocyte chemoattractant protein-1. J Neurosci Res 2002;70:784–93.
Bauer S, Rasika S, Han J, et al. Leukemia inhibitory factor is a key signal for injury-induced neurogenesis in the adult mouse olfactory epithelium. J Neurosci 2003;23:1792–803.
Michelini M, Franceschini V, Sihui Chen S, et al. Primate embryonic stem cells create their own niche while differentiating in three-dimensional culture systems. Cell Prolif 2006;39:217–29.
Awenagha O, Campbell G, Bird MM. Distribution of GAP-43, β-III tubulin and F-actin in developing and regenerating axons and their growth cones in vitro, following neurotrophin treatment. J Neurocyt 2003;32:1077–89.
Acknowledgments
The authors are grateful to Dr. Isabella Andreini for her valuable suggestions and generous help. Supporting grants to RPR by: C.N.R.: RSTL 2007; Italian Ministry of Health (Project “Stem 2001”; Istituto Zooprofilattico Sperimentale Lazio e Toscana, I.F. 2005–2007); Italian Ministry of University and Research (M.I.U.R.) (FIRB: “New Medical Engineering” and “Technologies in Oncology”); Joint Project “Kontakt” between the Ministries of Foreign Affairs of Italy and Czech Republic; Foundation “Stem Cells & Life” Pisa, Italy. Supporting Grants to VF by M.I.U.R.
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Franceschini, V., Bettini, S., Saccardi, R., Revoltella, R.P. (2009). Stem Cell Transplantation Supports the Repair of Injured Olfactory Neuroepithelium After Permanent Lesion. In: Baharvand, H. (eds) Trends in Stem Cell Biology and Technology. Humana Press. https://doi.org/10.1007/978-1-60327-905-5_16
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DOI: https://doi.org/10.1007/978-1-60327-905-5_16
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