Evidence map›Paper›PMID 33413614›Full record

ArticleStem cell research & therapy2021

PDGF-BB and IL-4 co-overexpression is a potential strategy to enhance mesenchymal stem cell-based bone regeneration.

Ning Zhang, Chi-Wen Lo, Takeshi Utsunomiya, Masahiro Maruyama, Ejun Huang, Claire Rhee, Qi Gao, Zhenyu Yao, Stuart B Goodman

Open access · goldAbstract read
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 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
4.6field-weighted citation impact, top 4% 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, 46 citations in OpenAlex.

  1. Article
  2. Discovery of Obacunone as a TGR5 Agonist fromInternational journal of molecular sciences · 2026
    Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. Transduction of Lentiviral Vectors andInternational journal of molecular sciences · 2025
    Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Review
  14. Article
  15. A new osteogenic protein isolated fromBioactive materials · 2023
    Article
  16. Article
  17. Therapeutic effects of MSCs, genetically modified MSCs, and NFĸB-inhibitor on chronic inflammatory osteolysis in aged mice.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2023
    Article
  18. Review
  19. Review
  20. Article
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 1 country.

Ning ZhangDepartment of Orthopaedic Surgery, Stanford University, Stanford, CA, USA.
Chi-Wen LoDepartment of Orthopaedic Surgery, Stanford University, Stanford, CA, USA.
Takeshi UtsunomiyaDepartment of Orthopaedic Surgery, Stanford University, Stanford, CA, USA.
Masahiro MaruyamaDepartment of Orthopaedic Surgery, Stanford University, Stanford, CA, USA.
Ejun HuangDepartment of Orthopaedic Surgery, Stanford University, Stanford, CA, USA.
Claire RheeDepartment of Orthopaedic Surgery, Stanford University, Stanford, CA, USA.
Qi GaoDepartment of Orthopaedic Surgery, Stanford University, Stanford, CA, USA.
Zhenyu YaoDepartment of Orthopaedic Surgery, Stanford University, Stanford, CA, USA. zhenyuy@stanford.edu.ORCID 0000-0002-1144-0621
Stuart B GoodmanDepartment of Orthopaedic Surgery, Stanford University, Stanford, CA, USA. goodbone@stanford.edu.
Stanford University · USStanford Medicine · US

Funding

Wear Particle Disease and NF-kappa B SignalingR01AR063717 · NIAMS · STANFORD UNIVERSITY · PI GOODMAN, STUART B · 2012 to 2021
$3.5M
Tissue Engineering Approaches for Improved Treatment of Early Stage Osteonecrosis of the HipR01AR072613 · NIAMS · STANFORD UNIVERSITY · PI GOODMAN, STUART B, YANG, YUNZHI · 2018 to 2022
$2.2M
Training In Orthopaedic Team ScienceT32AR067708 · NIAMS · JOHNS HOPKINS UNIVERSITY · PI JONES, LYNNE C., SHAFIQ, BABAR · 2015 to 2024
$2.0M
Customized MSCs to Enhance Healing of Bone DefectsR01AR073145 · NIAMS · STANFORD UNIVERSITY · PI GOODMAN, STUART B · 2018 to 2021
$1.4M
Cell-Based Autogenous Grafting for the Treatment of Femoral Head OsteonecrosisR34AR073505 · NIAMS · JOHNS HOPKINS UNIVERSITY · PI GOODMAN, STUART B, JONES, LYNNE C. · 2019 to 2020
$470k
NIAMS NIH HHS R01 AR063717NIAMS NIH HHS R01 AR072613NIAMS NIH HHS R01 AR073145NIAMS NIH HHS R34 AR073505NIAMS NIH HHS T32 AR067708
6 · The paper itself

Abstract

backgroundMesenchymal stem cell (MSC)-based therapy has the potential for immunomodulation and enhancement of tissue regeneration. Genetically modified MSCs that over-express specific cytokines, growth factors, or chemokines have shown great promise in pre-clinical studies. In this regard, the anti-inflammatory cytokine interleukin (IL)-4 converts pro-inflammatory M1 macrophages into an anti-inflammatory M2 phenotype; M2 macrophages mitigate chronic inflammation and enhance osteogenesis by MSC lineage cells. However, exposure to IL-4 prematurely inhibits osteogenesis of MSCs in vitro; furthermore, IL-4 overexpressing MSCs inhibit osteogenesis in vivo during the acute inflammatory period. Platelet-derived growth factor (PDGF)-BB has been shown to enhance osteogenesis of MSCs with a dose-dependent effect.

methodsIn this study, we generated a lentiviral vector that produces PDGF-BB under a weak promoter (phosphoglycerate kinase, PGK) and lentiviral vector producing IL-4 under a strong promoter (cytomegalovirus, CMV). We infected MSCs with PDGF-BB and IL-4-producing lentiviral vectors separately or in combination to investigate cell proliferation and viability, protein expression, and the capability for osteogenesis.

resultsPDGF-BB and IL-4 co-overexpression was observed in the co-infected MSCs and shown to enhance cell proliferation and viability, and osteogenesis compared to IL-4 overexpressing MSCs alone.

conclusionsOverexpression of PDGF-BB together with IL-4 mitigates the inhibitory effect of IL-4 on osteogenesis by IL-4 overexpressing MSCS. PDGF-BB and IL-4 overexpressing MSCs may be a potential strategy to facilitate osteogenesis in scenarios of both acute and chronic inflammation.

Indexed as

Mesenchymal Stem CellsBecaplerminBone RegenerationInterleukin-4OsteogenesisBecaplerminInterleukin-4Bone regenerationCo-overexpressionGenetically modified mesenchymal stem cellsInterleukin-4Platelet-derived growth factor

Identifiers

PMID33413614
PMCPMC7792350
OpenAlexW3120468619

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.