Evidence map›Paper›PMID 27075768›Full record

ArticleStem cells translational medicine2016

Using miRNA-mRNA Interaction Analysis to Link Biologically Relevant miRNAs to Stem Cell Identity Testing for Next-Generation Culturing Development.

Marian A E Crabbé, Kristel Gijbels, Aline Visser, David Craeye, Sara Walbers, Jef Pinxteren, Robert J Deans, Wim Annaert, Bart L T Vaes

Open access · goldAbstract read
In one paragraph

Article in Stem cells translational medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.8field-weighted citation impact, top 29% 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, 14 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

9 authors at 2 institutions in 2 countries.

Marian A E CrabbéReGenesys BVBA, Heverlee, Belgium Center for Human Genetics, KU Leuven, Leuven, Belgium VIB Center for the Biology of Disease, KU Leuven, Leuven, Belgium.
Kristel GijbelsReGenesys BVBA, Heverlee, Belgium.
Aline VisserReGenesys BVBA, Heverlee, Belgium.
David CraeyeReGenesys BVBA, Heverlee, Belgium.
Sara WalbersReGenesys BVBA, Heverlee, Belgium.
Jef PinxterenReGenesys BVBA, Heverlee, Belgium.
Robert J DeansRegenerative Medicine, Athersys Inc., Cleveland, Ohio, USA Rubius Therapeutics, Cambridge, Massachusetts, USA.
Wim AnnaertCenter for Human Genetics, KU Leuven, Leuven, Belgium VIB Center for the Biology of Disease, KU Leuven, Leuven, Belgium.
Bart L T VaesReGenesys BVBA, Heverlee, Belgium bvaes@regenesys.eu.
VIB-KU Leuven Center for Cancer Biology · BERubius Therapeutics (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

unlabelledTherapeutic benefit of stem cells has been demonstrated in multiple disease models and clinical trials. Robust quality assurance is imperative to make advancements in culturing procedures to enable large-scale cell manufacturing without hampering therapeutic potency. MicroRNAs (miRNAs or miRs) are shown to be master regulators of biological processes and are potentially ideal quality markers. We determined miRNA markers differentially expressed under nonclinical multipotent adult progenitor cell (MAPC) and mesenchymal stem cell (MSC) culturing conditions that regulate important stem cell features, such as proliferation and differentiation. These bone marrow-derived stem cell types were selected because they both exert therapeutic functions, but have different proliferative and regenerative capacities. To determine cell-specific marker miRNAs and assess their effects on stem cell qualities, a miRNA and mRNA profiling was performed on MAPCs and MSCs isolated from three shared donors. We applied an Ingenuity Pathway Analysis-based strategy that combined an integrated RNA profile analysis and a biological function analysis to determine the effects of miRNA-mRNA interactions on phenotype. This resulted in the identification of important miRNA markers linked to cell-cycle regulation and development, the most distinctive being MAPC marker miR-204-5p and MSC marker miR-335-5p, for which we provide in vitro validation of its function in differentiation and cell cycle regulation, respectively. Importantly, marker expression is maintained under xeno-free conditions and during bioreactor isolation and expansion of MAPC cultures. In conclusion, the identified biologically relevant miRNA markers can be used to monitor stem cell stability when implementing variations in culturing procedures. SIGNIFICANCE: Human adult marrow stromal stem cells have shown great potential in addressing unmet health care needs. Quality assurance is imperative to make advancements in large-scale manufacturing procedures. MicroRNAs are master regulators of biological processes and potentially ideal quality markers. MicroRNA and mRNA profiling data of two human adult stem cell types were correlated to biological functions in silico. Doing this provided evidence that differentially expressed microRNAs are involved in regulating specific stem cell features. Furthermore, expression of a selected microRNA panel was maintained in next-generation culturing platforms, demonstrating the robustness of microRNA profiling in stem cell comparability testing.

Indexed as

Bone Marrow CellsCell DifferentiationGene Expression ProfilingHumansMesenchymal Stem CellsMicroRNAsRNA, MessengerMicroRNAsRNA, MessengerBioreactorCell comparability testingMesenchymal stem cellMicroRNA profilingMultipotent adult progenitor cellXenobiotic-free

Identifiers

PMID27075768
PMCPMC4878327
OpenAlexW2336489823

What Socratic holds

Textmetadata
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 Socratic graph.