Evidence map›Paper›PMID 38321490›Full record

ArticleStem cell research & therapy2024

Osteogenic human MSC-derived extracellular vesicles regulate MSC activity and osteogenic differentiation and promote bone regeneration in a rat calvarial defect model.

Niyaz Al-Sharabi, Samih Mohamed-Ahmed, Siddharth Shanbhag, Carina Kampleitner, Rammah Elnour, Shuntaro Yamada, Neha Rana, Even Birkeland, Stefan Tangl, Reinhard Gruber and 1 more

Abstract read
In one paragraph

Article in Stem cell research & therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing 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

31 citing papers in PubMed.

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  8. Craniofacial Fracture and Secretome: A Systematic Review.Plastic and reconstructive surgery. Global open · 2026
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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

11 authors.

Niyaz Al-SharabiDepartment of Clinical Dentistry, Faculty of Medicine, Center for Translational Oral Research (TOR), University of Bergen, 5009, Bergen, Norway. N.Al-Sharabi@uib.no.ORCID 0000-0001-5526-5995
Samih Mohamed-AhmedDepartment of Clinical Dentistry, Faculty of Medicine, Center for Translational Oral Research (TOR), University of Bergen, 5009, Bergen, Norway.
Siddharth ShanbhagDepartment of Clinical Dentistry, Faculty of Medicine, Center for Translational Oral Research (TOR), University of Bergen, 5009, Bergen, Norway.
Carina KampleitnerKarl Donath Laboratory for Hard Tissue and Biomaterial Research, University Clinic of Dentistry, Medical University of Vienna, 1090, Vienna, Austria.
Rammah ElnourDepartment of Clinical Medicine, Faculty of Medicine, University of Bergen, 5009, Bergen, Norway.
Shuntaro YamadaDepartment of Clinical Dentistry, Faculty of Medicine, Center for Translational Oral Research (TOR), University of Bergen, 5009, Bergen, Norway.
Neha RanaDepartment of Clinical Dentistry, Faculty of Medicine, Center for Translational Oral Research (TOR), University of Bergen, 5009, Bergen, Norway.
Even BirkelandThe Proteomics Facility of the University of Bergen (PROBE), University of Bergen, 5021, Bergen, Norway.
Stefan TanglKarl Donath Laboratory for Hard Tissue and Biomaterial Research, University Clinic of Dentistry, Medical University of Vienna, 1090, Vienna, Austria.
Reinhard GruberAustrian Cluster for Tissue Regeneration, 1200, Vienna, Austria.
Kamal MustafaDepartment of Clinical Dentistry, Faculty of Medicine, Center for Translational Oral Research (TOR), University of Bergen, 5009, Bergen, Norway.

Funding

International Team for Implantology (Swiss) 2019International Team for Implantology (Swiss) 417L. Meltzers Høyskolefond 13190000/ 103517129L. Meltzers Høyskolefond 2022Trond Mohn stiftelse 2021TMT08Trond Mohn stiftelse 2022
6 · The paper itself

Abstract

backgroundThere is growing evidence that extracellular vesicles (EVs) play a crucial role in the paracrine mechanisms of transplanted human mesenchymal stem cells (hMSCs). Little is known, however, about the influence of microenvironmental stimuli on the osteogenic effects of EVs. This study aimed to investigate the properties and functions of EVs derived from undifferentiated hMSC (Naïve-EVs) and hMSC during the early stage of osteogenesis (Osteo-EVs). A further aim was to assess the osteoinductive potential of Osteo-EVs for bone regeneration in rat calvarial defects.

methodsEVs from both groups were isolated using size-exclusion chromatography and characterized by size distribution, morphology, flow cytometry analysis and proteome profiling. The effects of EVs (10 µg/ml) on the proliferation, migration, and osteogenic differentiation of cultured hMSC were evaluated. Osteo-EVs (50 µg) or serum-free medium (SFM, control) were combined with collagen membrane scaffold (MEM) to repair critical-sized calvarial bone defects in male Lewis rats and the efficacy was assessed using µCT, histology and histomorphometry.

resultsAlthough Osteo- and Naïve-EVs have similar characteristics, proteomic analysis revealed an enrichment of bone-related proteins in Osteo-EVs. Both groups enhance cultured hMSC proliferation and migration, but Osteo-EVs demonstrate greater efficacy in promoting in vitro osteogenic differentiation, as evidenced by increased expression of osteogenesis-related genes, and higher calcium deposition. In rat calvarial defects, MEM with Osteo-EVs led to greater and more consistent bone regeneration than MEM loaded with SFM.

conclusionsThis study discloses differences in the protein profile and functional effects of EVs obtained from naïve hMSC and hMSC during the early stage of osteogenesis, using different methods. The significant protein profile and cellular function of EVs derived from hMSC during the early stage of osteogenesis were further verified by a calvarial bone defect model, emphasizing the importance of using differentiated MSC to produce EVs for bone therapeutics.

Indexed as

Extracellular VesiclesMesenchymal Stem CellsAnimalsBone RegenerationCell DifferentiationHumansMaleOsteogenesisProteomicsRatsRats, Inbred LewBone regenerationExtracellular vesiclesMesenchymal stem cellsNaïve-EVsOsteo-EVsRat calvarial defects

Identifiers

PMID38321490
PMCPMC10848378

What Socratic 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 Socratic graph.