Evidence map›Paper›PMID 34563248›Full record

ArticleStem cell research & therapy2021

Human pluripotent stem cell-derived cartilaginous organoids promote scaffold-free healing of critical size long bone defects.

Wai Long Tam, Luís Freitas Mendes, Xike Chen, Raphaëlle Lesage, Inge Van Hoven, Elke Leysen, Greet Kerckhofs, Kathleen Bosmans, Yoke Chin Chai, Akihiro Yamashita and 4 more

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

Article in Stem cell research & therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed
9.6field-weighted citation impact, top 1% 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

63 citing papers in PubMed, 98 citations in OpenAlex.

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  19. Bone organoid construction and evolution.Journal of orthopaedic translation · 2025
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3 more citing papers are in PubMed but not listed here.

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

14 authors at 7 institutions in 4 countries.

Wai Long Tam *Laboratory for Developmental and Stem Cell Biology (DSB), Skeletal Biology and Engineering Research Center (SBE), KU Leuven, O&N1, Herestraat 49, Onderwijs en Navorsing 8th floor, bus 813, 3000, Leuven, Belgium.
Luís Freitas Mendes *Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, O&N 1 Herestraat 49 Bus 813, 3000, Leuven, Belgium.
Xike ChenPrometheus, Division of Skeletal Tissue Engineering, KU Leuven, O&N 1 Herestraat 49 Bus 813, 3000, Leuven, Belgium.
Raphaëlle LesagePrometheus, Division of Skeletal Tissue Engineering, KU Leuven, O&N 1 Herestraat 49 Bus 813, 3000, Leuven, Belgium.
Inge Van HovenLaboratory for Developmental and Stem Cell Biology (DSB), Skeletal Biology and Engineering Research Center (SBE), KU Leuven, O&N1, Herestraat 49, Onderwijs en Navorsing 8th floor, bus 813, 3000, Leuven, Belgium.
Elke LeysenLaboratory for Developmental and Stem Cell Biology (DSB), Skeletal Biology and Engineering Research Center (SBE), KU Leuven, O&N1, Herestraat 49, Onderwijs en Navorsing 8th floor, bus 813, 3000, Leuven, Belgium.
Greet KerckhofsPrometheus, Division of Skeletal Tissue Engineering, KU Leuven, O&N 1 Herestraat 49 Bus 813, 3000, Leuven, Belgium.
Kathleen BosmansPrometheus, Division of Skeletal Tissue Engineering, KU Leuven, O&N 1 Herestraat 49 Bus 813, 3000, Leuven, Belgium.
Yoke Chin ChaiPrometheus, Division of Skeletal Tissue Engineering, KU Leuven, O&N 1 Herestraat 49 Bus 813, 3000, Leuven, Belgium.
Akihiro YamashitaCenter for iPS Cell Research and Application (CiRA), Kyoto University, Kawahara-cho 53, Kyoto, 606-8507, Japan.
Noriyuki TsumakiCenter for iPS Cell Research and Application (CiRA), Kyoto University, Kawahara-cho 53, Kyoto, 606-8507, Japan.
Liesbet GerisPrometheus, Division of Skeletal Tissue Engineering, KU Leuven, O&N 1 Herestraat 49 Bus 813, 3000, Leuven, Belgium.
Scott J Roberts *Laboratory for Developmental and Stem Cell Biology (DSB), Skeletal Biology and Engineering Research Center (SBE), KU Leuven, O&N1, Herestraat 49, Onderwijs en Navorsing 8th floor, bus 813, 3000, Leuven, Belgium.
Frank P Luyten *Laboratory for Developmental and Stem Cell Biology (DSB), Skeletal Biology and Engineering Research Center (SBE), KU Leuven, O&N1, Herestraat 49, Onderwijs en Navorsing 8th floor, bus 813, 3000, Leuven, Belgium. frank.luyten@kuleuven.be.ORCID 0000-0003-3186-0276
KU Leuven · BEKyoto University · JPBekaert (Belgium) · BEHôpital Civil de Charleroi · BEPrometheus Research (United States) · USRega Institute for Medical Research · BERoyal Veterinary College · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundBones have a remarkable capacity to heal upon fracture. Yet, in large defects or compromised conditions healing processes become impaired, resulting in delayed or non-union. Current therapeutic approaches often utilize autologous or allogeneic bone grafts for bone augmentation. However, limited availability of these tissues and lack of predictive biological response result in limitations for clinical demands. Tissue engineering using viable cell-based implants is a strategic approach to address these unmet medical needs.

methodsHerein, the in vitro and in vivo cartilage and bone tissue formation potencies of human pluripotent stem cells were investigated. The induced pluripotent stem cells were specified towards the mesodermal lineage and differentiated towards chondrocytes, which subsequently self-assembled into cartilaginous organoids. The tissue formation capacity of these organoids was then challenged in an ectopic and orthotopic bone formation model.

resultsThe derived chondrocytes expressed similar levels of collagen type II as primary human articular chondrocytes and produced stable cartilage when implanted ectopically in vivo. Upon targeted promotion towards hypertrophy and priming with a proinflammatory mediator, the organoids mediated successful bridging of critical size long bone defects in immunocompromised mice.

conclusionsThese results highlight the promise of induced pluripotent stem cell technology for the creation of functional cartilage tissue intermediates that can be explored for novel bone healing strategies.

Indexed as

OrganoidsPluripotent Stem CellsAnimalsBone and BonesCartilageChondrocytesChondrogenesisHumansMiceTissue EngineeringBoneBone tissue engineeringCartilageEndochondral ossificationInduced pluripotent stem cellsOrganoid biologyPluripotent stem cellsStem cell technology

Identifiers

PMID34563248
PMCPMC8466996
OpenAlexW3202404851

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.