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Exfoliated Human Olfactory Neuroepithelium: A Source of Neural Progenitor Cells

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Abstract

Neural progenitor cells (NPC) contained in the human adult olfactory neuroepithelium (ONE) possess an undifferentiated state, the capability of self-renewal, the ability to generate neural and glial cells as well as being kept as neurospheres in cell culture conditions. Recently, NPC have been isolated from human or animal models using high-risk surgical methods. Therefore, it was necessary to improve methodologies to obtain and maintain human NPC as well as to achieve better knowledge of brain disorders. In this study, we propose the establishment and characterization of NPC cultures derived from the human olfactory neuroepithelium, using non-invasive procedures. Twenty-two healthy individuals (29.7 ± 4.5 years of age) were subjected to nasal exfoliation. Cells were recovered and kept as neurospheres under serum-free conditions. The neural progenitor origin of these neurospheres was determined by immunocytochemistry and qPCR. Their ability for self-renewal and multipotency was analyzed by clonogenic and differentiation assays, respectively. In the cultures, the ONE cells preserved the phenotype of the neurospheres. The expression levels of Nestin, Musashi, Sox2, and βIII-tubulin demonstrated the neural origin of the neurospheres; 48% of the cells separated could generate neurospheres, determining that they retained their self-renewal capacity. Neurospheres were differentiated in the absence of growth factors (EGF and FGF), and their multipotency ability was maintained as well. We were also able to isolate and grow human neural progenitor cells (neurospheres) through nasal exfoliates (non-invasive method) of the ONE from healthy adults, which is an extremely important contribution for the study of brain disorders and for the development of new therapies.

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Acknowledgments

This study was financed by Fondo de Investigación en Salud, IMSS (FIS; grant FIS/IMSS/PROT/G11/948), México. We thank Héctor Solis Chagoyan for his help to prepare part of the images.

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Authors and Affiliations

  1. Unidad de Investigación Médica en Genética Humana, Instituto Mexicano del Seguro Social, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Av. Cuauhtémoc No. 330, Col. Doctores, Delegación Cuauhtémoc, C.P. 06720, Ciudad de México, México

    Ana L. Jiménez-Vaca, Beatriz Hernández-de la Cruz, Fabio A. Salamanca-Gómez & Rosa Ma. Ordoñez-Razo

  2. Posgrado en Biología Experimental, Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana, San Rafael Atlixco No. 186, Col. Vicentina, Iztapalapa, 09340, Ciudad de México, México

    Ana L. Jiménez-Vaca

  3. Laboratorio de Neurofarmacología, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Calzada México Xochimilco 101, Col. San Lorenzo Huipulco, Delegación Tlalpan, 14370, Ciudad de México, México

    Gloria Benitez-King

  4. Departamento de Biología Molecular, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Calzada de Tlalpan No. 4502, Col. Sección XVI, 14080, Ciudad de México, México

    Víctor Ruiz

  5. Laboratorio de Neurogénesis, Subdirección de Investigaciones Clínicas, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Calzada México Xochimilco 101, Col. Col. San Lorenzo Huipulco, Delegación Tlalpan, 14370, Ciudad de México, México

    Gerardo B. Ramírez-Rodríguez & Leonardo Ortíz-López

  6. Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana, San Rafael Atlixco No. 186, Col. Vicentina, Delegación Iztapalapa, 09340, Ciudad de México, México

    Humberto González-Márquez

  7. Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del IPN, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Col. Casco de Santo Tomas, Delegación Miguel Hidalgo, 11340, Ciudad de México, México

    Israel Ramírez-Sánchez

  8. Departamento de Biología Celular, Centro de Investigación y Estudios Avanzados del IPN, Av. Instituto Politécnico Nacional 2508, Col. San Pedro Zacatenco, Delegación Gustavo A. Madero, México D.F, 07360, Ciudad de México, México

    Cristina Vélez-del Valle

Authors
  1. Ana L. Jiménez-Vaca
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  2. Gloria Benitez-King
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  3. Víctor Ruiz
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  4. Gerardo B. Ramírez-Rodríguez
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  5. Beatriz Hernández-de la Cruz
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  6. Fabio A. Salamanca-Gómez
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  7. Humberto González-Márquez
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  8. Israel Ramírez-Sánchez
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  9. Leonardo Ortíz-López
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  10. Cristina Vélez-del Valle
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  11. Rosa Ma. Ordoñez-Razo
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Corresponding author

Correspondence to Rosa Ma. Ordoñez-Razo.

Ethics declarations

After the informed consent form was obtained for the inclusion in this study, nasal exfoliates were obtained from 22 healthy adult individuals [10 females and 12 males; 32.5 years old (SEM ± 3.23)]. This study was approved by the Scientific and Ethics Committee of Health Research from the Instituto Mexicano del Seguro Social, Siglo XXI in accordance with the Declaration of Helsinki, 1964.

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The authors declare that they have no conflict of interest.

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Jiménez-Vaca, A.L., Benitez-King, G., Ruiz, V. et al. Exfoliated Human Olfactory Neuroepithelium: A Source of Neural Progenitor Cells. Mol Neurobiol 55, 2516–2523 (2018). https://doi.org/10.1007/s12035-017-0500-z

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  • DOI: https://doi.org/10.1007/s12035-017-0500-z

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