Evidence map›Paper›PMID 29467016›Full record

ArticleStem cell research & therapy2018

Advancing osteochondral tissue engineering: bone morphogenetic protein, transforming growth factor, and fibroblast growth factor signaling drive ordered differentiation of periosteal cells resulting in stable cartilage and bone formation in vivo.

L F Mendes, H Katagiri, W L Tam, Y C Chai, L Geris, S J Roberts, F P Luyten

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stem cell research & therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed, 2 pooled it
7.7field-weighted citation impact, top 2% 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

33 citing papers in PubMed, 2 syntheses or guidelines pooled it, 63 citations in OpenAlex.

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  8. Recapitulation ofJournal of orthopaedic translation · 2025
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  13. Frontiers in bioengineering and biotechnology · 2024
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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 2 institutions in 2 countries.

L F MendesTissue Engineering Laboratory, Skeletal Biology and Engineering Research Center, KU Leuven, Campus Gasthuisberg O&N 1, Herestraat 49, bus 813, 3000, Leuven, Belgium.
H KatagiriTissue Engineering Laboratory, Skeletal Biology and Engineering Research Center, KU Leuven, Campus Gasthuisberg O&N 1, Herestraat 49, bus 813, 3000, Leuven, Belgium.
W L TamTissue Engineering Laboratory, Skeletal Biology and Engineering Research Center, KU Leuven, Campus Gasthuisberg O&N 1, Herestraat 49, bus 813, 3000, Leuven, Belgium.
Y C ChaiTissue Engineering Laboratory, Skeletal Biology and Engineering Research Center, KU Leuven, Campus Gasthuisberg O&N 1, Herestraat 49, bus 813, 3000, Leuven, Belgium.
L GerisTissue Engineering Laboratory, Skeletal Biology and Engineering Research Center, KU Leuven, Campus Gasthuisberg O&N 1, Herestraat 49, bus 813, 3000, Leuven, Belgium.
S J RobertsTissue Engineering Laboratory, Skeletal Biology and Engineering Research Center, KU Leuven, Campus Gasthuisberg O&N 1, Herestraat 49, bus 813, 3000, Leuven, Belgium.
F P LuytenTissue Engineering Laboratory, Skeletal Biology and Engineering Research Center, KU Leuven, Campus Gasthuisberg O&N 1, Herestraat 49, bus 813, 3000, Leuven, Belgium. frank.luyten@uzleuven.be.
KU Leuven · BEUniversity College London · GB

Funding

European Research Council 279100
6 · The paper itself

Abstract

backgroundChondrogenic mesenchymal stem cells (MSCs) have not yet been used to address the clinical demands of large osteochondral joint surface defects. In this study, self-assembling tissue intermediates (TIs) derived from human periosteum-derived stem/progenitor cells (hPDCs) were generated and validated for stable cartilage formation in vivo using two different animal models.

methodshPDCs were aggregated and cultured in the presence of a novel growth factor (GF) cocktail comprising of transforming growth factor (TGF)-β1, bone morphogenetic protein (BMP)2, growth differentiation factor (GDF)5, BMP6, and fibroblast growth factor (FGF)2. Quantitative polymerase chain reaction (PCR) and immunohistochemistry were used to study in vitro differentiation. Aggregates were then implanted ectopically in nude mice and orthotopically in critical-size osteochondral defects in nude rats and evaluated by microcomputed tomography (µCT) and immunohistochemistry.

resultsGene expression analysis after 28 days of in vitro culture revealed the expression of early and late chondrogenic markers and a significant upregulation of NOGGIN as compared to human articular chondrocytes (hACs). Histological examination revealed a bilayered structure comprising of chondrocytes at different stages of maturity. Ectopically, TIs generated both bone and mineralized cartilage at 8 weeks after implantation. Osteochondral defects treated with TIs displayed glycosaminoglycan (GAG) production, type-II collagen, and lubricin expression. Immunostaining for human nuclei protein suggested that hPDCs contributed to both subchondral bone and articular cartilage repair.

conclusionOur data indicate that in vitro derived osteochondral-like tissues can be generated from hPDCs, which are capable of producing bone and cartilage ectopically and behave orthotopically as osteochondral units.

Indexed as

Tissue EngineeringAnimalsAntigens, DifferentiationBone Morphogenetic Protein 2Bone Morphogenetic Protein 6CartilageCell DifferentiationFibroblast Growth Factor 2HeterograftsHumansMiceMice, NudePeriosteumSignal TransductionStem CellsStem Cell TransplantationAntigens, DifferentiationBMP2 protein, humanBMP6 protein, humanBone Morphogenetic Protein 2Bone Morphogenetic Protein 6Fibroblast Growth Factor 2TGFB1 protein, humanTransforming Growth Factor beta1Cartilage tissue engineeringGrowth factorsOsteochondral defectPeriosteal cellsSubchondral bone regeneration

Identifiers

PMID29467016
PMCPMC5822604
OpenAlexW2807611965

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.