Multiple sclerosis patient-specific primary neurons differentiated from urinary renal epithelial cells via induced pluripotent stem cells

Megan G. Massa, Barbara Gisevius, Sarah Hirschberg, Lisa Hinz, Matthias Schmidt, Ralf Gold, Nora Prochnow, Aiden Haghikia

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Article numbere0155274
JournalPLoS ONE
Volume11
Issue number5
DOIs
Publication statusPublished - 1 May 2016

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Induced Pluripotent Stem Cells
sclerosis
kidney cells
Stem cells
Neurons
Multiple Sclerosis
epithelial cells
neurons
Epithelial Cells
Kidney
Screening
Animals
Embryoid Bodies
drugs
Proximal Kidney Tubule
Preclinical Drug Evaluations
proximal tubules
Neural Tube
Nerve Growth Factors
Medical Genetics

Cite this

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. In: PLoS ONE. 2016 ; Vol. 11, No. 5.
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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.

In: PLoS ONE, Vol. 11, No. 5, e0155274, 01.05.2016.

Research output: Contribution to JournalArticleAcademicpeer-review

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