Evidence map›Paper›PMID 37502943›Full record

ArticleResearch square2023

Multichannel bridges and NSC synergize to enhance axon regeneration, myelination, synaptic reconnection, and recovery after SCI.

Usha Nekanti, Pooja Sakthivel, Atena Zahedi, Dana A Creasman, Rebecca A Nishi, Courtney M Dumont, Katja M Piltti, Glenn L Guardamondo, Norbert Hernandez, Xingyuan Chen and 13 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in Research square, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed, 3 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors at 6 institutions in 2 countries.

Usha NekantiSue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA, USA.
Pooja SakthivelSue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA, USA.
Atena ZahediSue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA, USA.
Dana A CreasmanSue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA, USA.
Rebecca A NishiSue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA, USA.
Courtney M DumontDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.
Katja M PilttiSue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA, USA.
Glenn L GuardamondoSue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA, USA.
Norbert HernandezSue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA, USA.
Xingyuan ChenSue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA, USA.
Hui SongSue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA, USA.
Xiaoxiao LinDepartment of Anatomy and Neurobiology, University of California, Irvine, CA, USA.
Joshua MartinezSue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA, USA.
Lillian OnSue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA, USA.
Anita LakatosSue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA, USA.
Kiran PawarDepartment of Medicine, University of British Columbia - Vancouver, Canada.ORCID 0000-0001-7475-6570
Brian T DavidDepartment of Neurosurgery, Rush University Medical Center, Chicago, Illinois, USA.
Zhiling GuoDepartment of Medicine & Susan Samueli Integrative Health Institute, University of California, Irvine, CA, USA.
Stephanie K SeidlitsDepartment of Biomedical Engineering, The University of Texas at Austin, TX, USA.
Xiangmin XuDepartment of Anatomy and Neurobiology, University of California, Irvine, CA, USA.
Lonnie D SheaDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0002-9296-9673
Brian J CummingsSue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA, USA.
Aileen J AndersonSue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA, USA.
University of California, Irvine · USRush University Medical Center · USThe University of Texas at Austin · USUniversity of British Columbia · CAUniversity of Miami · USUniversity of Michigan · US

Funding

Controlled Release Scaffolds for Nerve RegenerationR01EB005678 · NIBIB · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ANDERSON, AILEEN J, SHEA, LONNIE D · 2007 to 2018
$6.0M
NIBIB NIH HHS R01 EB005678
6 · The paper itself

Abstract

Regeneration in the injured spinal cord is limited by physical and chemical barriers. Acute implantation of a multichannel poly(lactide-co-glycolide) (PLG) bridge mechanically stabilizes the injury, modulates inflammation, and provides a permissive environment for rapid cellularization and robust axonal regrowth through this otherwise inhibitory milieu. However, without additional intervention, regenerated axons remain largely unmyelinated (<10%), limiting functional repair. While transplanted human neural stem cells (hNSC) myelinate axons after spinal cord injury (SCI), hNSC fate is highly influenced by the SCI inflammatory microenvironment, also limiting functional repair. Accordingly, we investigated the combination of PLG scaffold bridges with hNSC to improve histological and functional outcome after SCI. In vitro, hNSC culture on a PLG scaffold increased oligodendroglial lineage selection after inflammatory challenge. In vivo, acute PLG bridge implantation followed by chronic hNSC transplantation demonstrated a robust capacity of donor human cells to migrate into PLG bridge channels along regenerating axons and integrate into the host spinal cord as myelinating oligodendrocytes and synaptically integrated neurons. Axons that regenerated through the PLG bridge formed synaptic circuits that connected ipsilateral forelimb muscle to contralateral motor cortex. hNSC transplantation significantly enhanced the total number of regenerating and myelinated axons identified within the PLG bridge. Finally, the combination of acute bridge implantation and hNSC transplantation exhibited robust improvement in locomotor recovery vs. control and hNSC transplant alone. These data identify a successful novel strategy to enhance neurorepair through a temporally layered approach using acute bridge implantation and chronic cell transplantation to spare tissue, promote regeneration, and maximize the function of new axonal connections.

Identifiers

PMID37502943
PMCPMC10371146
OpenAlexW4384828943

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.