Evidence map›Paper›PMID 33377628›Full record

ArticleStem cells translational medicine2021

Systemic DKK1 neutralization enhances human adipose-derived stem cell mediated bone repair.

Stefano Negri, Yiyun Wang, Takashi Sono, Qizhi Qin, Ginny Ching-Yun Hsu, Masnsen Cherief, Jiajia Xu, Seungyong Lee, Robert J Tower, Victoria Yu and 5 more

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

Article in Stem cells translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
1.3field-weighted citation impact, top 19% 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

14 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Stem Cells and Bone Tissue Engineering.Life (Basel, Switzerland) · 2024
    Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. STAT6 Blockade AbrogatesFrontiers in immunology · 2022
    Article
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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

15 authors at 3 institutions in 2 countries.

Stefano NegriDepartment of Pathology, Johns Hopkins University, Baltimore, Maryland, USA.ORCID 0000-0003-2218-6654
Yiyun WangDepartment of Pathology, Johns Hopkins University, Baltimore, Maryland, USA.ORCID 0000-0003-0775-4377
Takashi SonoDepartment of Pathology, Johns Hopkins University, Baltimore, Maryland, USA.
Qizhi QinDepartment of Pathology, Johns Hopkins University, Baltimore, Maryland, USA.
Ginny Ching-Yun HsuDepartment of Pathology, Johns Hopkins University, Baltimore, Maryland, USA.
Masnsen CheriefDepartment of Pathology, Johns Hopkins University, Baltimore, Maryland, USA.
Jiajia XuDepartment of Pathology, Johns Hopkins University, Baltimore, Maryland, USA.
Seungyong LeeDepartment of Pathology, Johns Hopkins University, Baltimore, Maryland, USA.
Robert J TowerDepartment of Orthopaedic Surgery, Johns Hopkins University, Baltimore, Maryland, USA.
Victoria YuDepartment of Pathology, Johns Hopkins University, Baltimore, Maryland, USA.
Abhi PiplaniDepartment of Pathology, Johns Hopkins University, Baltimore, Maryland, USA.
Carolyn A MeyersDepartment of Pathology, Johns Hopkins University, Baltimore, Maryland, USA.
Kristen BroderickDepartment of Plastic Surgery, Johns Hopkins University, Baltimore, Maryland, USA.
Min LeeSchool of Dentistry, University of California Los Angeles, Los Angeles, California, USA.
Aaron W JamesDepartment of Pathology, Johns Hopkins University, Baltimore, Maryland, USA.
Johns Hopkins University · USUniversity of California, Los Angeles · USUniversity of Verona · IT

Funding

Direct and indirect contributions of perivascular stem cells to bone healingR01AR070773 · NIAMS · JOHNS HOPKINS UNIVERSITY · PI JAMES, AARON W · 2017 to 2021
$1.4M
NELL-1 isoforms for the systemic treatment of osteoporosisK08AR068316 · NIAMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI JAMES, AARON W · 2015 to 2019
$534k
Role of sensory nerves in cranial bone repairR21DE027922 · NIDCR · JOHNS HOPKINS UNIVERSITY · PI CLEMENS, THOMAS L, JAMES, AARON W · 2018 to 2019
$450k
NIAMS NIH HHS K08 AR068316NIAMS NIH HHS R01 AR070773NIDCR NIH HHS R21 DE027922
6 · The paper itself

Abstract

Progenitor cells from adipose tissue are able to induce bone repair; however, inconsistent or unreliable efficacy has been reported across preclinical and clinical studies. Soluble inhibitory factors, such as the secreted Wnt signaling antagonists Dickkopf-1 (DKK1), are expressed to variable degrees in human adipose-derived stem cells (ASCs), and may represent a targetable "molecular brake" on ASC mediated bone repair. Here, anti-DKK1 neutralizing antibodies were observed to increase the osteogenic differentiation of human ASCs in vitro, accompanied by increased canonical Wnt signaling. Human ASCs were next engrafted into a femoral segmental bone defect in NOD-Scid mice, with animals subsequently treated with systemic anti-DKK1 or isotype control during the repair process. Human ASCs alone induced significant but modest bone repair. However, systemic anti-DKK1 induced an increase in human ASC engraftment and survival, an increase in vascular ingrowth, and ultimately improved bone repair outcomes. In summary, anti-DKK1 can be used as a method to augment cell-mediated bone regeneration, and could be particularly valuable in the contexts of impaired bone healing such as osteoporotic bone repair.

Indexed as

Adipose TissueAntibodies, NeutralizingCell DifferentiationIntercellular Signaling Peptides and ProteinsOsteogenesisAnimalsHumansMiceMice, Inbred NODMice, SCIDStem CellsAntibodies, NeutralizingDKK1 protein, humanIntercellular Signaling Peptides and Proteinsadipose stem celladipose stromal cellbone healingbone repairbone tissue engineeringmesenchymal stem cellWnt signaling

Identifiers

PMID33377628
PMCPMC7980212
OpenAlexW3114574027

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.