Cargando…

Multiple Sclerosis Patient-Specific Primary Neurons Differentiated from Urinary Renal Epithelial Cells via Induced Pluripotent Stem Cells

As multiple sclerosis research progresses, it is pertinent to continue to develop suitable paradigms to allow for ever more sophisticated investigations. Animal models of multiple sclerosis, despite their continuing contributions to the field, may not be the most prudent for every experiment. Indeed...

Descripción completa

Detalles Bibliográficos
Autores principales: Massa, Megan G., Gisevius, Barbara, Hirschberg, Sarah, Hinz, Lisa, Schmidt, Matthias, Gold, Ralf, Prochnow, Nora, Haghikia, Aiden
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4861271/
https://www.ncbi.nlm.nih.gov/pubmed/27158987
http://dx.doi.org/10.1371/journal.pone.0155274
_version_ 1782431193505988608
author Massa, Megan G.
Gisevius, Barbara
Hirschberg, Sarah
Hinz, Lisa
Schmidt, Matthias
Gold, Ralf
Prochnow, Nora
Haghikia, Aiden
author_facet Massa, Megan G.
Gisevius, Barbara
Hirschberg, Sarah
Hinz, Lisa
Schmidt, Matthias
Gold, Ralf
Prochnow, Nora
Haghikia, Aiden
author_sort Massa, Megan G.
collection PubMed
description As multiple sclerosis research progresses, it is pertinent to continue to develop suitable paradigms to allow for ever more sophisticated investigations. Animal models of multiple sclerosis, despite their continuing contributions to the field, may not be the most prudent for every experiment. Indeed, such may be either insufficient to reflect the functional impact of human genetic variations or unsuitable for drug screenings. Thus, we have established a cell- and patient-specific paradigm to provide an in vitro model within which to perform future genetic investigations. Renal proximal tubule epithelial cells were isolated from multiple sclerosis patients’ urine and transfected with pluripotency-inducing episomal factors. Subsequent induced pluripotent stem cells were formed into embryoid bodies selective for ectodermal lineage, resulting in neural tube-like rosettes and eventually neural progenitor cells. Differentiation of these precursors into primary neurons was achieved through a regimen of neurotrophic and other factors. These patient-specific primary neurons displayed typical morphology and functionality, also staining positive for mature neuronal markers. The development of such a non-invasive procedure devoid of permanent genetic manipulation during the course of differentiation, in the context of multiple sclerosis, provides an avenue for studies with a greater cell- and human-specific focus, specifically in the context of genetic contributions to neurodegeneration and drug discovery.
format Online
Article
Text
id pubmed-4861271
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-48612712016-05-13 Multiple Sclerosis Patient-Specific Primary Neurons Differentiated from Urinary Renal Epithelial Cells via Induced Pluripotent Stem Cells Massa, Megan G. Gisevius, Barbara Hirschberg, Sarah Hinz, Lisa Schmidt, Matthias Gold, Ralf Prochnow, Nora Haghikia, Aiden PLoS One Research Article As multiple sclerosis research progresses, it is pertinent to continue to develop suitable paradigms to allow for ever more sophisticated investigations. Animal models of multiple sclerosis, despite their continuing contributions to the field, may not be the most prudent for every experiment. Indeed, such may be either insufficient to reflect the functional impact of human genetic variations or unsuitable for drug screenings. Thus, we have established a cell- and patient-specific paradigm to provide an in vitro model within which to perform future genetic investigations. Renal proximal tubule epithelial cells were isolated from multiple sclerosis patients’ urine and transfected with pluripotency-inducing episomal factors. Subsequent induced pluripotent stem cells were formed into embryoid bodies selective for ectodermal lineage, resulting in neural tube-like rosettes and eventually neural progenitor cells. Differentiation of these precursors into primary neurons was achieved through a regimen of neurotrophic and other factors. These patient-specific primary neurons displayed typical morphology and functionality, also staining positive for mature neuronal markers. The development of such a non-invasive procedure devoid of permanent genetic manipulation during the course of differentiation, in the context of multiple sclerosis, provides an avenue for studies with a greater cell- and human-specific focus, specifically in the context of genetic contributions to neurodegeneration and drug discovery. Public Library of Science 2016-05-09 /pmc/articles/PMC4861271/ /pubmed/27158987 http://dx.doi.org/10.1371/journal.pone.0155274 Text en © 2016 Massa et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Massa, Megan G.
Gisevius, Barbara
Hirschberg, Sarah
Hinz, Lisa
Schmidt, Matthias
Gold, Ralf
Prochnow, Nora
Haghikia, Aiden
Multiple Sclerosis Patient-Specific Primary Neurons Differentiated from Urinary Renal Epithelial Cells via Induced Pluripotent Stem Cells
title Multiple Sclerosis Patient-Specific Primary Neurons Differentiated from Urinary Renal Epithelial Cells via Induced Pluripotent Stem Cells
title_full Multiple Sclerosis Patient-Specific Primary Neurons Differentiated from Urinary Renal Epithelial Cells via Induced Pluripotent Stem Cells
title_fullStr Multiple Sclerosis Patient-Specific Primary Neurons Differentiated from Urinary Renal Epithelial Cells via Induced Pluripotent Stem Cells
title_full_unstemmed Multiple Sclerosis Patient-Specific Primary Neurons Differentiated from Urinary Renal Epithelial Cells via Induced Pluripotent Stem Cells
title_short Multiple Sclerosis Patient-Specific Primary Neurons Differentiated from Urinary Renal Epithelial Cells via Induced Pluripotent Stem Cells
title_sort multiple sclerosis patient-specific primary neurons differentiated from urinary renal epithelial cells via induced pluripotent stem cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4861271/
https://www.ncbi.nlm.nih.gov/pubmed/27158987
http://dx.doi.org/10.1371/journal.pone.0155274
work_keys_str_mv AT massamegang multiplesclerosispatientspecificprimaryneuronsdifferentiatedfromurinaryrenalepithelialcellsviainducedpluripotentstemcells
AT giseviusbarbara multiplesclerosispatientspecificprimaryneuronsdifferentiatedfromurinaryrenalepithelialcellsviainducedpluripotentstemcells
AT hirschbergsarah multiplesclerosispatientspecificprimaryneuronsdifferentiatedfromurinaryrenalepithelialcellsviainducedpluripotentstemcells
AT hinzlisa multiplesclerosispatientspecificprimaryneuronsdifferentiatedfromurinaryrenalepithelialcellsviainducedpluripotentstemcells
AT schmidtmatthias multiplesclerosispatientspecificprimaryneuronsdifferentiatedfromurinaryrenalepithelialcellsviainducedpluripotentstemcells
AT goldralf multiplesclerosispatientspecificprimaryneuronsdifferentiatedfromurinaryrenalepithelialcellsviainducedpluripotentstemcells
AT prochnownora multiplesclerosispatientspecificprimaryneuronsdifferentiatedfromurinaryrenalepithelialcellsviainducedpluripotentstemcells
AT haghikiaaiden multiplesclerosispatientspecificprimaryneuronsdifferentiatedfromurinaryrenalepithelialcellsviainducedpluripotentstemcells