Evidence map›Paper›PMID 30098570›Full record

ArticleBiomaterials2018

Optimal electrical stimulation boosts stem cell therapy in nerve regeneration.

Jian Du, Gehua Zhen, Huanwen Chen, Shuming Zhang, Liming Qing, Xiuli Yang, Gabsang Lee, Hai-Quan Mao, Xiaofeng Jia

Erratum issuedOpen access · greenAbstract read
In one paragraph

Article in Biomaterials, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 68 papers.

0numbers the graph read from it
0cells of the map it votes in
68citing papers in PubMed
5.4field-weighted citation impact, top 3% 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

68 citing papers in PubMed, 144 citations in OpenAlex.

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8 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 1 country.

Jian DuDepartment of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Gehua ZhenDepartment of Orthopaedics, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
Huanwen ChenDepartment of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Shuming ZhangDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA; Department of Materials Science and Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
Liming QingDepartment of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Xiuli YangDepartment of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Gabsang LeeDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
Hai-Quan MaoDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA; Department of Materials Science and Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
Xiaofeng JiaDepartment of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, 21201, USA; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA; Department of Orthopedics, University of Maryland School of Medicine, Baltimore, MD, 21201, USA; Department of Anatomy Neurobiology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA; Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. Electronic address: xjia@som.umaryland.edu.
Johns Hopkins University · USUniversity of Maryland, Baltimore · USJohns Hopkins Medicine · US

Funding

Brain Monitoring and Therapeutic Hypothermia after Cardiac ArrestR01HL118084 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI JIA, XIAOFENG · 2013 to 2018
$1.9M
Brain Recovery after Cardiac Arrest with Metabolic Glycoengineered Stem CellsR01NS110387 · NINDS · UNIVERSITY OF MARYLAND BALTIMORE · PI JIA, XIAOFENG · 2018 to 2022
$1.7M
NHLBI NIH HHS R01 HL118084NINDS NIH HHS R01 NS110387
6 · The paper itself

Abstract

Peripheral nerve injuries often lead to incomplete recovery and contribute to significant disability to approximately 360,000 people in the USA each year. Stem cell therapy holds significant promise for peripheral nerve regeneration, but maintenance of stem cell viability and differentiation potential in vivo are still major obstacles for translation. Using a made-in-house 96-well vertical electrical stimulation (ES) platform, we investigated the effects of different stimulating pulse frequency, duration and field direction on human neural crest stem cell (NCSC) differentiation. We observed dendritic morphology with enhanced neuronal differentiation for NCSCs cultured on cathodes subject to 20 Hz, 100μs pulse at a potential gradient of 200 mV/mm. We further evaluated the effect of a novel cell-based therapy featuring optimized pulsatile ES of NCSCs for in vivo transplantation following peripheral nerve regeneration. 15 mm critical-sized sciatic nerve injuries were generated with subsequent surgical repair in sixty athymic nude rats. Injured animals were randomly assigned into five groups (N = 12 per group): blank control, ES, NCSC, NCSC + ES, and autologous nerve graft. The optimized ES was applied immediately after surgical repair for 1 h in ES and NCSC + ES groups. Recovery was assessed by behavioral (CatWalk gait analysis), wet muscle-mass, histomorphometric, and immunohistochemical analyses at either 6 or 12 weeks after surgery (N = 6 per group). Gastrocnemius muscle wet mass measurements in ES + NCSC group were comparable to autologous nerve transplantation and significantly higher than other groups (p < 0.05). Quantitative histomorphometric analysis and catwalk gait analysis showed similar improvements by ES on NCSCs (p < 0.05). A higher number of viable NCSCs was shown via immunochemical analysis, with higher Schwann cell (SC) differentiation in the NCSC + ES group compared to the NCSC group (p < 0.05). Overall, ES on NCSC transplantation significantly enhanced nerve regeneration after injury and repair, and was comparable to autograft treatment. Thus, ES can be a potent alternative to biochemical and physical cues for modulating stem cell survival and differentiation. This novel cell-based intervention presents an effective and safe approach for improved outcomes after peripheral nerve repair.

Indexed as

AnimalsCell DifferentiationCells, CulturedElectric StimulationHumansImmunohistochemistryNerve RegenerationNeural CrestNeural Stem CellsNeurogenesisPeripheral Nerve InjuriesRatsStem Cell TransplantationElectrical stimulationHuman neural crest stem cellNerve regenerationPeripheral nerve injuryPluripotent stem cells

Identifiers

PMID30098570
PMCPMC6201278
OpenAlexW2884614177

What OpenQuestion holds

Textmetadata
LicenceTDM
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.