Evidence map›Paper›PMID 31992369›Full record

ArticleStem cell research & therapy2020

Exosomes from bone marrow mesenchymal stem cells enhance fracture healing through the promotion of osteogenesis and angiogenesis in a rat model of nonunion.

Lu Zhang, Guangjun Jiao, Shanwu Ren, Xiaoqian Zhang, Ci Li, Wenliang Wu, Hongliang Wang, Haichun Liu, Hongming Zhou, Yunzhen Chen

Open access · goldAbstract read
In one paragraph

Article in Stem cell research & therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 204 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
204citing papers in PubMed, 3 pooled it
15.4field-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

204 citing papers in PubMed, 3 syntheses or guidelines pooled it, 356 citations in OpenAlex.

  1. Pooled it
  2. Consequences of Aging on Bone.Aging and disease · 2023
    Pooled it
  3. Pooled it
  4. Article
  5. Review
  6. Extracellular Vesicles and Their Role in Osteogenesis.Bioengineering (Basel, Switzerland) · 2026
    Review
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  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
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  15. Article
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  18. Article
  19. Clinical Applications of Extracellular Vesicles: Promises and Pitfalls.International journal of molecular sciences · 2026
    Review
  20. Review

144 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

10 authors at 2 institutions in 1 country.

Lu ZhangDepartment of Spine Surgery, Shandong University Qilu Hospital, Jinan, China.
Guangjun JiaoDepartment of Spine Surgery, Shandong University Qilu Hospital, Jinan, China.
Shanwu RenDepartment of Spine Surgery, Shandong University Qilu Hospital, Jinan, China.
Xiaoqian ZhangDepartment of Radiology, Shandong University Qilu Hospital, Qingdao, Qingdao, China.
Ci LiDepartment of Spine Surgery, Shandong University Qilu Hospital, Jinan, China.
Wenliang WuDepartment of Spine Surgery, Shandong University Qilu Hospital, Jinan, China.
Hongliang WangDepartment of Spine Surgery, Shandong University Qilu Hospital, Jinan, China.
Haichun LiuDepartment of Spine Surgery, Shandong University Qilu Hospital, Jinan, China.
Hongming ZhouDepartment of Spine Surgery, Shandong University Qilu Hospital, Jinan, China.
Yunzhen ChenDepartment of Spine Surgery, Shandong University Qilu Hospital, Jinan, China. qilucyz@yeah.net.ORCID 0000-0001-8447-9001
Qilu Hospital of Shandong University · CNLinyi People's Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAs important players in cell-to-cell communication, exosomes (exo) are believed to play a similar role in promoting fracture healing. This study investigated whether exosomes derived from bone marrow mesenchymal stem cells (BMMSC-Exos) could improve fracture healing of nonunion.

methodsBMMSC-Exos were isolated and transplanted into the fracture site in a rat model of femoral nonunion (Exo group) every week. Moreover, equal volumes of phosphate-buffered saline (PBS) and exosome-depleted conditioned medium (CM-Exo) were injected into the femoral fracture sites of the rats in the control and CM-Exo groups. Bone healing processes were recorded and evaluated by radiographic methods on weeks 8, 14 and 20 after surgery. Osteogenesis and angiogenesis at the fracture sites were evaluated by radiographic and histological methods on postoperative week 20. The expression levels of osteogenesis- or angiogenesis-related genes were evaluated in vitro by western blotting and immunohistochemistry. The ability to internalize exosomes was assessed using the PKH26 assay. Altered proliferation and migration of human umbilical vein endothelial cells (HUVECs) and mouse embryo osteoblast precursor cells (MC3TE-E1s) treated with BMMSC-Exos were determined by utilizing EdU incorporation, immunofluorescence staining, and scratch wound assay. The angiogenesis ability of HUVECs was evaluated through tube formation assays. Finally, to explore the effect of exosomes in osteogenesis via the BMP-2/Smad1/RUNX2 signalling pathway, the BMP-2 inhibitors noggin and LDN193189 were utilized, and their subsequent effects were observed.

resultsBMMSC-Exos were observed to be spherical with a diameter of approximately 122 nm. CD9, CD63 and CD81 were expressed. Transplantation of BMMSC-Exos obviously enhanced osteogenesis, angiogenesis and bone healing processes in a rat model of femoral nonunion. BMMSC-Exos were taken up by HUVECs and MC3T3-E1 in vitro, and their proliferation and migration were also improved. Finally, experiments with BMP2 inhibitors confirmed that the BMP-2/Smad1/RUNX2 signalling pathway played an important role in the pro-osteogenesis induced by BMMSC-Exos and enhanced fracture healing of nonunion.

conclusionsOur findings suggest that transplantation of BMMSC-Exos exerts a critical effect on the treatment of nonunion by promoting osteogenesis and angiogenesis. This promoting effect might be ascribed to the activation of the BMP-2/Smad1/RUNX2 and the HIF-1α/VEGF signalling pathways.

Indexed as

AnimalsDisease Models, AnimalExosomesFracture HealingHumansMaleMesenchymal Stem CellsOsteogenesisRatsAngiogenesisExosomesNonunionOsteogenesis

Identifiers

PMID31992369
PMCPMC6986095
OpenAlexW3007395396

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.