Evidence map›Paper›PMID 30635031›Full record

ArticleStem cell research & therapy2019

Exosomes secreted by endothelial progenitor cells accelerate bone regeneration during distraction osteogenesis by stimulating angiogenesis.

Yachao Jia, Yu Zhu, Shuo Qiu, Jia Xu, Yimin Chai

Open access · goldAbstract read
In one paragraph

Article in Stem cell research & therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
106citing papers in PubMed, 2 pooled it
9.0field-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

106 citing papers in PubMed, 2 syntheses or guidelines pooled it, 180 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Extracellular Vesicles and Their Role in Osteogenesis.Bioengineering (Basel, Switzerland) · 2026
    Review
  5. Review
  6. Review
  7. Review
  8. Review
  9. Review
  10. Article
  11. Article
  12. Review
  13. Review
  14. Review
  15. Article
  16. Review
  17. Exosomes promise better bone regeneration.Regenerative therapy · 2025
    Review
  18. Roles of skeletal muscle-derived exosomes in osteoporosis.Journal of translational medicine · 2025
    Review
  19. Endothelial Progenitor Cells: Disease Markers and Potential Therapy in Kidney Disease.Journal of the American Society of Nephrology : JASN · 2025
    Review
  20. Review

46 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

5 authors at 1 institution in 1 country.

Yachao JiaDepartment of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Yishan Rd 600, Shanghai, 200233, People's Republic of China.
Yu ZhuDepartment of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Yishan Rd 600, Shanghai, 200233, People's Republic of China.
Shuo QiuDepartment of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Yishan Rd 600, Shanghai, 200233, People's Republic of China.
Jia XuDepartment of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Yishan Rd 600, Shanghai, 200233, People's Republic of China. xujia0117@126.com.
Yimin ChaiDepartment of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Yishan Rd 600, Shanghai, 200233, People's Republic of China. ymchai@sjtu.edu.cn.ORCID 0000-0002-1972-5971
Shanghai Jiao Tong University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDistraction osteogenesis (DO) is an effective but lengthy procedure to fully induce bone regeneration in large bone defects. Accumulating evidence supports the role of exosomes secreted by endothelial progenitor cells (EPC-Exos) in stimulating angiogenesis, which is closely coupled with osteogenesis. This study aimed to investigate whether EPC-Exos promote bone regeneration during DO in rats.

methodsExosomes were isolated from the supernatants of rat bone marrow EPCs via ultracentrifugation and characterized via transmission electron microscopy, tunable resistive pulse sensing analysis, and western blot analysis. Unilateral tibial DO models were generated using 68 Sprague-Dawley rats with a distraction rate of 0.5 mm per day for 10 days. After local injection of EPC-Exos into the distraction gaps after distraction, the therapeutic effects of EPC-Exos on bone regeneration and angiogenesis were assessed via X-ray, micro-computed tomography (micro-CT), and biomechanical and histological analyses. Pro-angiogenic effects and the potential mechanism underlying the effects of EPC-Exos on human umbilical vein endothelial cells were subsequently evaluated via in vitro assays including Cell Counting Kit-8, wound healing, tube formation, and western blot assays.

resultsEPC-Exos were spherical or cup-shaped vesicles ranging from 50 to 150 nm in diameter and expressed markers including CD9, Alix, and TSG101. X-ray, micro-CT, and histological analyses revealed that bone regeneration was markedly accelerated in rats treated with EPC-Exos. The distracted tibias from the Exos group also displayed enhanced mechanical properties. Moreover, vessel density was higher in the Exos group than in the control group. In addition, in vitro analyses revealed that EPC-Exos enhanced the proliferation, migration, and angiogenic capacity of endothelial cells in an miR-126-dependent manner. Further, EPC-Exos downregulated SPRED1 and activated Raf/ERK signaling.

conclusionsThe present results show that EPC-Exos accelerate bone regeneration during DO by stimulating angiogenesis, suggesting their use as a novel method to shorten the treatment duration of DO.

Indexed as

AnimalsBone RegenerationCell DifferentiationCell ProliferationEndothelial Progenitor CellsExosomesGene Expression Regulation, DevelopmentalHumansMesenchymal Stem CellsMicroRNAsNeovascularization, PhysiologicOsteogenesisOsteogenesis, Distractionraf KinasesRatsRepressor ProteinsMicroRNAsMIRN126 microRNA, ratraf KinasesRepressor ProteinsSpred1 protein, ratAngiogenesisBone regenerationDistraction osteogenesisEndothelial progenitor cellsExosomes

Identifiers

PMID30635031
PMCPMC6329174
OpenAlexW2911886552

What OpenQuestion holds

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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.