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A unique neuroendocrine cell model derived from the human foetal neural crest

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Abstract

Purpose

Nowadays, no human neuroendocrine cell models derived from the neural crest are available. In this study, we present non-transformed long-term primary Neural Crest Cells (NCCs) isolated from the trunk region of the neural crest at VIII–XII gestational weeks of human foetuses obtained from voluntary legal abortion.

Methods and results

In NCC, quantitative real-time RT PCR demonstrated the expression of neural crest specifier genes, such as Snail1, Snail2/SLUG, Sox10, FoxD3, c-Myc, and p75NTR. Moreover, these cell populations expressed stemness markers (such as Nanog and nestin), as well as markers of motility and invasion (TAGLN, MMP9, CXCR4, and CXCR7), and of neuronal/glial differentiation (MAP2, GFAP, SYP, and TAU). Functional analysis demonstrated that these cells not only possessed high migration properties, but most importantly, they expressed markers of sympatho-adrenal lineage, such as ASCL1 and tyrosine hydroxylase (TH). Moreover, the expression of TH increased after the induction with two different protocols of differentiation towards neuronal and sympatho-adrenal phenotypes. Finally, exposure to conditioned culture media from NCC induced a mature phenotype in a neuronal cell model (namely SH-SY5Y), suggesting that NCC may also act like Schwann precursors.

Conclusion

This unique human cell model provides a solid tool for future studies addressing the bases of human neural crest-derived neuroendocrine tumours.

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Acknowledgements

This manuscript is dedicated to the memory of Susanna Benvenuti, an invaluable friend and a talented researcher, who designed this study and played an active role in the experimental work.

Funding

This work was supported by AIRC and Fondazione Cassa di Risparmio di Firenze (Project Code: 19515).

Author information

Author notes

  1. E. Rapizzi and S. Benvenuti have equally contributed to the work.

Authors and Affiliations

  1. Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy

    E. Rapizzi, E. Sarchielli, B. Mazzanti & G. B. Vannelli

  2. Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Viale Pieraccini 6, 50139, Florence, Italy

    S. Benvenuti, C. Deledda, S. Martinelli, B. Fibbi, P. Luciani, G. Marroncini, M. Maggi, M. Mannelli, M. Luconi & A. Peri

  3. Genetics and Molecular Medicine Unit, Anna Meyer Children’s University Hospital, Florence, Italy

    M. Pantaleo

  4. Istituto Nazionale Biostrutture e Biosistemi (INBB), viale delle Medaglie d’Oro 305, 00136, Rome, Italy

    M. Maggi & M. Luconi

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  1. E. Rapizzi
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Contributions

ER, SB, MM, and AP conceived the project and designed the experimental plan; ER, SB, CD, SM, ES, BF, PL, BM, MP, GM, and GBV performed the experiments and analysed the data; ER, SB, MM, ML, GBV, MM, and AP interpreted the results; ER, SB, MM, MM, ML, and AP wrote the manuscript.

Corresponding author

Correspondence to M. Luconi.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical statement

Legal abortion was performed in the authorized hospital Azienda Ospedaliero-Universitaria Careggi and tissue sampling was performed after informed consent from patients. The study protocols were approved by the Local Ethical Committee (protocol n° 6783-04, 1st February 2002, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy).

Research involving human participants and/or animals

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained by all individual participants included in the study.

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Rapizzi, E., Benvenuti, S., Deledda, C. et al. A unique neuroendocrine cell model derived from the human foetal neural crest. J Endocrinol Invest 43, 1259–1269 (2020). https://doi.org/10.1007/s40618-020-01213-9

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  • DOI: https://doi.org/10.1007/s40618-020-01213-9

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