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Neural crest stem cells from human epidermis of aged donors maintain their multipotency in vitro and in vivo

Moghadasi Boroujeni, Samaneh and Koontz, Alison and Tseropoulos, Georgios and Kerosuo, Laura and Mehrotra, Pihu and Bajpai, Vivek K. and Selvam, Surya Rajan and Lei, Pedro and Bronner, Marianne E. and Andreadis, Stelios T. (2019) Neural crest stem cells from human epidermis of aged donors maintain their multipotency in vitro and in vivo. Scientific Reports, 9 . Art. No. 9750. ISSN 2045-2322. PMCID PMC6611768. https://resolver.caltech.edu/CaltechAUTHORS:20190715-074911175

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Abstract

Neural crest (NC) cells are multipotent stem cells that arise from the embryonic ectoderm, delaminate from the neural tube in early vertebrate development and migrate throughout the developing embryo, where they differentiate into various cell lineages. Here we show that multipotent and functional NC cells can be derived by induction with a growth factor cocktail containing FGF2 and IGF1 from cultures of human inter-follicular keratinocytes (KC) isolated from elderly donors. Adult NC cells exhibited longer doubling times as compared to neonatal NC cells, but showed limited signs of cellular senescence despite the advanced age of the donors and exhibited significantly younger epigenetic age as compared to KC. They also maintained their multipotency, as evidenced by their ability to differentiate into all NC-specific lineages including neurons, Schwann cells, melanocytes, and smooth muscle cells (SMC). Notably, upon implantation into chick embryos, adult NC cells behaved similar to their embryonic counterparts, migrated along stereotypical pathways and contributed to multiple NC derivatives in ovo. These results suggest that KC-derived NC cells may provide an easily accessible, autologous source of stem cells that can be used for treatment of neurodegenerative diseases or as a model system for studying disease pathophysiology and drug development.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1038/s41598-019-46140-9DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6611768/PubMed CentralArticle
ORCID:
AuthorORCID
Kerosuo, Laura0000-0001-6710-3512
Bronner, Marianne E.0000-0003-4274-1862
Additional Information:© 2019 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. Received 26 February 2019; Accepted 24 June 2019; Published 05 July 2019. The authors declare no competing interests. This work was supported by grants from the National Institutes of Health R01 EB023114 (S.T.A., M.E.B.) and the New York Stem Cell Science NYSTEM (Contract #C30290GG, S.T.A.). Author Contributions: Samaneh Moghadasi Boroujeni: Designing and performing experiments, data analysis and interpretation, writing of the manuscript. Alison Koontz, Laura Kerosuo, Marianne E. Bronner: In ovo implantation experiments design, data analysis and interpretation, writing of the manuscript; Pihu Mehrotra: Developed neuron differentiation protocol; Vivek K. Bajpai: Designing experiments, troubleshooting. Surya Rajan Selvam: Performed melanocyte and Schwann cell differentiation experiments. Georgios Tseropoulos, Pedro Lei: Keratinocyte isolation from human skin tissues. Stelios T. Andreadis: Conceived the idea, design of experiments, analysis and interpretation of data, manuscript writing and project supervision.
Funders:
Funding AgencyGrant Number
NIHR01 EB023114
New York Stem Cell Science (NYSTEM)C30290GG
Subject Keywords:Adult stem cells; Multipotent stem cells
PubMed Central ID:PMC6611768
Record Number:CaltechAUTHORS:20190715-074911175
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20190715-074911175
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:97138
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:15 Jul 2019 16:46
Last Modified:03 Oct 2019 21:28

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