Evidence map›Paper›PMID 29566057›Full record

Trial reportPloS one2018

Development of an in vitro potency assay for human skeletal muscle derived cells.

Marco Thurner, Faheem Asim, Dorota Garczarczyk-Asim, Katrin Janke, Martin Deutsch, Eva Margreiter, Jakob Troppmair, Rainer Marksteiner

Open access · goldAbstract readClinical Trial, Phase IIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.6field-weighted citation impact, top 32% 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

7 citing papers in PubMed, 15 citations in OpenAlex.

  1. Trial
  2. Article
  3. Potency Assay Development: A Keystone for Clinical Use.Advances in experimental medicine and biology · 2023
    Article
  4. Article
  5. Article
  6. Article
  7. Article
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

8 authors at 2 institutions in 1 country.

Marco ThurnerInnovacell Biotechnologie AG, Science Park, Innsbruck, Austria.ORCID 0000-0002-4702-9551
Faheem AsimInnovacell Biotechnologie AG, Science Park, Innsbruck, Austria.
Dorota Garczarczyk-AsimInnovacell Biotechnologie AG, Science Park, Innsbruck, Austria.
Katrin JankeInnovacell Biotechnologie AG, Science Park, Innsbruck, Austria.
Martin DeutschInnovacell Biotechnologie AG, Science Park, Innsbruck, Austria.
Eva MargreiterInnovacell Biotechnologie AG, Science Park, Innsbruck, Austria.
Jakob TroppmairDaniel Swarovski Research Laboratory, Department of Visceral, Transplant, and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria.
Rainer MarksteinerInnovacell Biotechnologie AG, Science Park, Innsbruck, Austria.
Innovacell Biotechnologie (Austria) · ATInnsbruck Medical University · AT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPotency is a quantitative measure of the desired biological function of an advanced therapy medicinal product (ATMP) and is a prerequisite for market approval application (MAA). To assess the potency of human skeletal muscle-derived cells (SMDCs), which are currently investigated in clinical trials for the regeneration of skeletal muscle defects, we evaluated acetylcholinesterase (AChE), which is expressed in skeletal muscle and nervous tissue of all mammals.

methodsCD56+ SMDCs were separated from CD56- SMDCs by magnetic activated cell sorting (MACS) and both differentiated in skeletal muscle differentiation medium. AChE activity of in vitro differentiated SMDCs was correlated with CD56 expression, fusion index, cell number, cell doubling numbers, differentiation markers and compared to the clinical efficacy in patients treated with SMDCs against fecal incontinence.

resultsCD56- SMDCs did not form multinucleated myotubes and remained low in AChE activity during differentiation. CD56+ SMDCs generated myotubes and increased in AChE activity during differentiation. AChE activity was found to accurately reflect the number of CD56+ SMDCs in culture, their fusion competence, and cell doubling number. In patients with fecal incontinence responding to SMDCs treatment, the improvement of clinical symptoms was positively linked with the AChE activity of the SMDCs injected. DISCUSSION: AChE activity was found to truly reflect the in vitro differentiation status of SMDCs and to be superior to the mere use of surface markers as it reflects not only the number of myogenic SMDCs in culture but also their fusion competence and population doubling number, thus combining cell quality and quantification of the expected mode of action (MoA) of SMDCs. Moreover, the successful in vitro validation of the assay proves its suitability for routine use. Most convincingly, our results demonstrate a link between clinical efficacy and the AChE activity of the SMDCs preparations used for the treatment of fecal incontinence. Thus, we recommend using AChE activity of in vitro differentiated SMDCs as a potency measure in end stage (phase III) clinical trials using SMDCs for skeletal muscle regeneration and subsequent market approval application (MAA).

Indexed as

AcetylcholinesteraseAnal CanalBiopsyCD56 AntigenCell CountCell DifferentiationCells, CulturedCell SeparationCell TransplantationConsumer Product SafetyDouble-Blind MethodEnzyme AssaysFecal IncontinenceFemaleFlow CytometryGPI-Linked ProteinsAcetylcholinesteraseACHE protein, humanCD56 AntigenGPI-Linked ProteinsNCAM1 protein, humanPlacebos

Identifiers

PMID29566057
PMCPMC5864011
OpenAlexW2791116289

What OpenQuestion holds

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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.