Evidence map›Paper›PMID 28917625›Full record

ArticleCytotherapy2018

Reduced neuroprotective potential of the mesenchymal stromal cell secretome with ex vivo expansion, age and progressive multiple sclerosis.

Pamela Sarkar, Juliana Redondo, Kevin Kemp, Mark Ginty, Alastair Wilkins, Neil J Scolding, Claire M Rice

Open access · hybridAbstract read
In one paragraph

Article in Cytotherapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
2.2field-weighted citation impact, top 12% 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

23 citing papers in PubMed, 49 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 1 institution in 1 country.

Pamela SarkarSchool of Clinical Sciences, University of Bristol, Bristol, UK.
Juliana RedondoSchool of Clinical Sciences, University of Bristol, Bristol, UK.
Kevin KempSchool of Clinical Sciences, University of Bristol, Bristol, UK.
Mark GintySchool of Clinical Sciences, University of Bristol, Bristol, UK.
Alastair WilkinsSchool of Clinical Sciences, University of Bristol, Bristol, UK.
Neil J ScoldingSchool of Clinical Sciences, University of Bristol, Bristol, UK.
Claire M RiceSchool of Clinical Sciences, University of Bristol, Bristol, UK. Electronic address: c.m.rice@bristol.ac.uk.
University of Bristol · GB

Funding

Medical Research Council MR/K004166/1
6 · The paper itself

Abstract

backgroundClinical trials using ex vivo expansion of autologous mesenchymal stromal cells (MSCs) are in progress for several neurological diseases including multiple sclerosis (MS). Given that environment alters MSC function, we examined whether in vitro expansion, increasing donor age and progressive MS affect the neuroprotective properties of the MSC secretome.

methodsComparative analyses of neuronal survival in the presence of MSC-conditioned medium (MSCcm) isolated from control subjects (C-MSCcm) and those with MS (MS-MSCcm) were performed following (1) trophic factor withdrawal and (2) nitric oxide-induced neurotoxicity.

resultsReduced neuronal survival following trophic factor withdrawal was seen in association with increasing expansion of MSCs in vitro and MSC donor age. Controlling for these factors, there was an independent, negative effect of progressive MS. In nitric oxide neurotoxicity, MSCcm-mediated neuroprotection was reduced when C-MSCcm was isolated from higher-passage MSCs and was negatively associated with increasing MSC passage number and donor age. Furthermore, the neuroprotective effect of MSCcm was lost when MSCs were isolated from patients with MS. DISCUSSION: Our findings have significant implications for MSC-based therapy in neurodegenerative conditions, particularly for autologous MSC therapy in MS. Impaired neuroprotection mediated by the MSC secretome in progressive MS may reflect reduced reparative potential of autologous MSC-based therapy in MS and it is likely that the causes must be addressed before the full potential of MSC-based therapy is realized. Additionally, we anticipate that understanding the mechanisms responsible will contribute new insights into MS pathogenesis and may also be of wider relevance to other neurodegenerative conditions.

Indexed as

Disease ProgressionAgingCell ProliferationCell SurvivalCulture Media, ConditionedHumansMesenchymal Stem CellsMiddle AgedMultiple SclerosisNeuronsNeuroprotectionNeuroprotective AgentsNitric OxideCulture Media, ConditionedNeuroprotective AgentsNitric Oxidecell therapymesenchymal stromal cellsmultiple sclerosisneuroprotection

Identifiers

PMID28917625
PMCPMC5758344
OpenAlexW2751352478

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.