Evidence map›Paper›PMID 27343168›Full record

ArticleStem cells translational medicine2016

Differentiation and Characterization of Dopaminergic Neurons From Baboon Induced Pluripotent Stem Cells.

Douglas A Grow, DeNard V Simmons, Jorge A Gomez, Matthew J Wanat, John R McCarrey, Carlos A Paladini, Christopher S Navara

Open access · goldAbstract read
In one paragraph

Article in Stem cells translational medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.4field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 18 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 1 country.

Douglas A GrowDepartment of Biology, University of Texas at San Antonio, San Antonio, Texas, USA; San Antonio Cellular Therapeutics Institute, San Antonio, Texas, USA; University of Texas at San Antonio Neurosciences Institute, San Antonio, Texas, USA.
DeNard V SimmonsDepartment of Biology, University of Texas at San Antonio, San Antonio, Texas, USA; University of Texas at San Antonio Neurosciences Institute, San Antonio, Texas, USA.
Jorge A GomezDepartment of Biology, University of Texas at San Antonio, San Antonio, Texas, USA; University of Texas at San Antonio Neurosciences Institute, San Antonio, Texas, USA.
Matthew J WanatDepartment of Biology, University of Texas at San Antonio, San Antonio, Texas, USA; University of Texas at San Antonio Neurosciences Institute, San Antonio, Texas, USA.
John R McCarreyDepartment of Biology, University of Texas at San Antonio, San Antonio, Texas, USA; San Antonio Cellular Therapeutics Institute, San Antonio, Texas, USA;
Carlos A PaladiniDepartment of Biology, University of Texas at San Antonio, San Antonio, Texas, USA; University of Texas at San Antonio Neurosciences Institute, San Antonio, Texas, USA.
Christopher S NavaraDepartment of Biology, University of Texas at San Antonio, San Antonio, Texas, USA; San Antonio Cellular Therapeutics Institute, San Antonio, Texas, USA; Christopher.navara@utsa.edu.
The University of Texas at San Antonio · USNeurosciences Institute · USSouth Texas Accelerated Research Therapeutics · US

Funding

The Southwest National Primate Research Center Supplement- Infrastructure improvements of ABSL2 holding areasP51OD011133 · OD · TEXAS BIOMEDICAL RESEARCH INSTITUTE · PI Larry S. Schlesinger · 2012 to 2026
$129.7M
UTSA RISE Research Training ProgramR25GM060655 · NIGMS · UNIVERSITY OF TEXAS SAN ANTONIO · PI BAREA-RODRIGUEZ, EDWIN J · 2000 to 2022
$21.6M
Cellular mechanisms of dopamine neuron burstingR01MH107229 · NIMH · UNIVERSITY OF TEXAS SAN ANTONIO · PI HSIEH, JENNY · 2016 to 2020
$1.8M
The Synaptic Origin of Reward Prediction Error Signal in Dopaminergic NeuronsR01DA030530 · NIDA · UNIVERSITY OF TEXAS SAN ANTONIO · PI PALADINI, CARLOS ANTONIO · 2011 to 2015
$1.4M
Cellular Mechanisms of Dopamine Neuron BurstingR01MH079276 · NIMH · UNIVERSITY OF TEXAS SAN ANTONIO · PI PALADINI, CARLOS ANTONIO · 2007 to 2011
$1.2M
CRF and Stress Modulation of Phasic Dopamine Release and BehaviorR00DA033386 · NIDA · UNIVERSITY OF TEXAS SAN ANTONIO · PI WANAT, MATTHEW J. · 2014 to 2016
$724k
CRF and Stress Modulation of Phasic Dopamine Release and BehaviorK99DA033386 · NIDA · UNIVERSITY OF WASHINGTON · PI WANAT, MATTHEW J. · 2013 to 2013
$108k
NIDA NIH HHS K99 DA033386NIDA NIH HHS R00 DA033386NIDA NIH HHS R01 DA030530NIGMS NIH HHS R25 GM060655NIH HHS P51 OD011133NIMH NIH HHS R01 MH079276NIMH NIH HHS R01 MH107229
6 · The paper itself

Abstract

unlabelled: The progressive death of dopamine producing neurons in the substantia nigra pars compacta is the principal cause of symptoms of Parkinson's disease (PD). Stem cells have potential therapeutic use in replacing these cells and restoring function. To facilitate development of this approach, we sought to establish a preclinical model based on a large nonhuman primate for testing the efficacy and safety of stem cell-based transplantation. To this end, we differentiated baboon fibroblast-derived induced pluripotent stem cells (biPSCs) into dopaminergic neurons with the application of specific morphogens and growth factors. We confirmed that biPSC-derived dopaminergic neurons resemble those found in the human midbrain based on cell type-specific expression of dopamine markers TH and GIRK2. Using the reverse transcriptase quantitative polymerase chain reaction, we also showed that biPSC-derived dopaminergic neurons express PAX6, FOXA2, LMX1A, NURR1, and TH genes characteristic of this cell type in vivo. We used perforated patch-clamp electrophysiology to demonstrate that biPSC-derived dopaminergic neurons fired spontaneous rhythmic action potentials and high-frequency action potentials with spike frequency adaption upon injection of depolarizing current. Finally, we showed that biPSC-derived neurons released catecholamines in response to electrical stimulation. These results demonstrate the utility of the baboon model for testing and optimizing the efficacy and safety of stem cell-based therapeutic approaches for the treatment of PD. SIGNIFICANCE: Functional dopamine neurons were produced from baboon induced pluripotent stem cells, and their properties were compared to baboon midbrain cells in vivo. The baboon has advantages as a clinically relevant model in which to optimize the efficacy and safety of stem cell-based therapies for neurodegenerative diseases, such as Parkinson's disease. Baboons possess crucial neuroanatomical and immunological similarities to humans, and baboon pluripotent stem cells can be differentiated into functional neurons that mimic those in the human brain, thus laying the foundation for the utility of the baboon model for evaluating stem cell therapies.

Indexed as

AnimalsCell Culture TechniquesCell DifferentiationDopaminergic NeuronsImmunohistochemistryInduced Pluripotent Stem CellsModels, AnimalNeural Stem CellsPapioPatch-Clamp TechniquesPolymerase Chain ReactionBaboonDopaminergic neuronsInduced pluripotent stem cellsNeural differentiationParkinson’s disease

Identifiers

PMID27343168
PMCPMC4996432
OpenAlexW2462216989

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.