Evidence map›Paper›PMID 31848365›Full record

ArticleScientific reports2019

Tissue-type plasminogen activator-primed human iPSC-derived neural progenitor cells promote motor recovery after severe spinal cord injury.

Yasuhiro Shiga, Akina Shiga, Pinar Mesci, HyoJun Kwon, Coralie Brifault, John H Kim, Jacob J Jeziorski, Chanond Nasamran, Seiji Ohtori, Alysson R Muotri and 2 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
0.9field-weighted citation impact, top 30% 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

9 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Review
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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

12 authors at 3 institutions in 2 countries.

Yasuhiro ShigaDepartment of Anesthesiology, University of California San Diego, La Jolla, CA, 92093, USA.
Akina ShigaDepartment of Orthopaedic Surgery and Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan.
Pinar MesciDepartments of Pediatrics and Cellular and Molecular Medicine, and the Stem Cell Program, University of California, San Diego, CA, 92037-0695, USA.
HyoJun KwonDepartment of Anesthesiology, University of California San Diego, La Jolla, CA, 92093, USA.
Coralie BrifaultDepartment of Anesthesiology, University of California San Diego, La Jolla, CA, 92093, USA.
John H KimDepartment of Anesthesiology, University of California San Diego, La Jolla, CA, 92093, USA.
Jacob J JeziorskiDepartments of Pediatrics and Cellular and Molecular Medicine, and the Stem Cell Program, University of California, San Diego, CA, 92037-0695, USA.
Chanond NasamranCenter for Computational Biology & Bioinformatics (CCBB), University of California, San Diego, La Jolla, CA, 92093, USA.
Seiji OhtoriDepartment of Orthopaedic Surgery and Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan.
Alysson R MuotriDepartments of Pediatrics and Cellular and Molecular Medicine, and the Stem Cell Program, University of California, San Diego, CA, 92037-0695, USA.
Steven L GoniasDepartment of Pathology, University of California San Diego, La Jolla, CA, 92093, USA.
Wendy M CampanaDepartment of Anesthesiology, University of California San Diego, La Jolla, CA, 92093, USA. wcampana@health.ucsd.edu.
University of California, San Diego · USChiba University · JPVA San Diego Healthcare System · US

Funding

UC San Diego Clinical and Translational Research InstituteUL1TR001442 · NCATS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FIRESTEIN, GARY S, HOGARTH, MICHAEL · 2015 to 2024
$88.3M
Single-cell approaches to deconvolution of disease-associated signalsU19MH107367 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MUOTRI, ALYSSON R. · 2015 to 2019
$15.0M
Proteogenetics of Autism Spectrum DisordersR01MH100175 · NIMH · SCRIPPS RESEARCH INSTITUTE, THE · PI MUOTRI, ALYSSON R., YATES III, JOHN R · 2013 to 2025
$7.4M
Regulation of Inflammation by the Fibrinolytic SystemR01HL136395 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GONIAS, STEVEN L. · 2017 to 2025
$3.5M
Integrative functional genomic study of pathways impacted by recurrent autism CNVR01MH108528 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI IAKOUCHEVA, LILIA M, MUOTRI, ALYSSON R. · 2016 to 2020
$2.6M
Evaluating the effect of splicing mutations on isoform networks in autismR01MH109885 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI IAKOUCHEVA, LILIA M, MUOTRI, ALYSSON R. · 2016 to 2020
$2.5M
The Impact of L1retrotransposition in the nervous systemR01MH094753 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MUOTRI, ALYSSON R. · 2011 to 2015
$1.9M
Schwann Cell NMDA Receptor in PNS InjuryR01NS097590 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CAMPANA, WENDY M., GONIAS, STEVEN L. · 2017 to 2020
$1.4M
NHLBI NIH HHS R01 HL136395NIMH NIH HHS R01 MH094753NIMH NIH HHS R01 MH100175NIMH NIH HHS R01 MH108528NIMH NIH HHS R01 MH109885NIMH NIH HHS U19 MH107367NINDS NIH HHS R01 NS097590U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) UL1TR001442
6 · The paper itself

Abstract

The goal of stem cell therapy for spinal cord injury (SCI) is to restore motor function without exacerbating pain. Induced pluripotent stem cells (iPSC) may be administered by autologous transplantation, avoiding immunologic challenges. Identifying strategies to optimize iPSC-derived neural progenitor cells (hiNPC) for cell transplantation is an important objective. Herein, we report a method that takes advantage of the growth factor-like and anti-inflammatory activities of the fibrinolysis protease, tissue plasminogen activator tPA, without effects on hemostasis. We demonstrate that conditioning hiNPC with enzymatically-inactive tissue-type plasminogen activator (EI-tPA), prior to grafting into a T3 lesion site in a clinically relevant severe SCI model, significantly improves motor outcomes. EI-tPA-primed hiNPC grafted into lesion sites survived, differentiated, acquired markers of motor neuron maturation, and extended βIII-tubulin-positive axons several spinal segments below the lesion. Importantly, only SCI rats that received EI-tPA primed hiNPC demonstrated significantly improved motor function, without exacerbating pain. When hiNPC were treated with EI-tPA in culture, NMDA-R-dependent cell signaling was initiated, expression of genes associated with stemness (Nestin, Sox2) was regulated, and thrombin-induced cell death was prevented. EI-tPA emerges as a novel agent capable of improving the efficacy of stem cell therapy in SCI.

Indexed as

AnimalsCell DifferentiationHumansInduced Pluripotent Stem CellsMotor NeuronsNeural Stem CellsNeurogenesisRatsRecovery of FunctionSpinal CordSpinal Cord InjuriesStem CellsStem Cell TransplantationTissue Plasminogen ActivatorTissue Plasminogen Activator

Identifiers

PMID31848365
PMCPMC6917728
OpenAlexW2996592615

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.