Evidence map›Paper›PMID 34313927›Full record

SynthesisStem cell reviews and reports2022

MSC-Derived Extracellular Vesicles in Preclinical Animal Models of Bone Injury: A Systematic Review and Meta-Analysis.

Aidan M Kirkham, Adrian J M Bailey, Alvin Tieu, Harinad B Maganti, Joshua Montroy, Risa Shorr, T Mark Campbell, Dean A Fergusson, Manoj M Lalu, Heidi Elmoazzen and 1 more

Abstract readMeta-AnalysisSystematic Review
PubMed Publisher
In one paragraph

Synthesis in Stem cell reviews and reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 5 pooled it
1.1field-weighted citation impact, top 22% 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

16 citing papers in PubMed, 5 syntheses or guidelines pooled it, 21 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Review
  7. Review
  8. Review
  9. Review
  10. Anatomical implant region - a critical determinant for the osteogenic potency of small extracellular vesicles and rhBMP-2.European journal of trauma and emergency surgery : official publication of the European Trauma Society · 2025
    Article
  11. Review
  12. Review
  13. Review
  14. Article
  15. Review
  16. Review
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

11 authors at 4 institutions in 1 country.

Aidan M KirkhamStem Cells, Canadian Blood Services, Ottawa, ON, Canada.
Adrian J M BaileyStem Cells, Canadian Blood Services, Ottawa, ON, Canada.
Alvin TieuClinical Epidemiology, Ottawa Hospital Research Institute, 501 Smyth Rd, Box 704, Ottawa, ON, K1H 8L6, Canada.
Harinad B MagantiStem Cells, Canadian Blood Services, Ottawa, ON, Canada.
Joshua MontroyClinical Epidemiology, Ottawa Hospital Research Institute, 501 Smyth Rd, Box 704, Ottawa, ON, K1H 8L6, Canada.
Risa ShorrMedical Information and Education Services, The Ottawa Hospital, Ottawa, ON, Canada.
T Mark CampbellRegenerative Medicine, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
Dean A FergussonClinical Epidemiology, Ottawa Hospital Research Institute, 501 Smyth Rd, Box 704, Ottawa, ON, K1H 8L6, Canada.
Manoj M LaluClinical Epidemiology, Ottawa Hospital Research Institute, 501 Smyth Rd, Box 704, Ottawa, ON, K1H 8L6, Canada.
Heidi ElmoazzenStem Cells, Canadian Blood Services, Ottawa, ON, Canada.
David S AllanStem Cells, Canadian Blood Services, Ottawa, ON, Canada. daallan@toh.ca.
Ottawa Hospital Research InstituteCanadian Blood Services · CAOttawa Hospital · CAUniversity of Ottawa · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectiveMesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) are a promising treatment for bone injuries, although studies remain preclinical. A systematic review and meta-analysis can assess the efficacy of MSC-EVs and identify treatment aspects associated with enhanced bone repair.

methodsEnglish language, preclinical, controlled, in vivo studies identified in our systematic search (up to May 8, 2020) examining the use of MSC-EVs in bone healing were included. Risk of bias (ROB) was assessed using the SYRCLE tool. Aggregate Data Meta-Analysis was performed to determine the effect of MSC-EVs on Bone Volume/Total Volume (BV/TV) and New Bone Formation (NBF).

resultsThirteen studies were included. Twelve reported either BV/TV or NBF and were included in meta-analysis. ROB was unclear in all studies. Overall, MSC-EVs displayed benefit in terms of bone healing for both BV/TV (22.2% mean difference (MD); 95% CI: 15.8-28.5%, p < 0.001) and NBF (26.1% MD; 10.3-41.8%, p = 0.001) versus controls. Substantial heterogeneity, however, was observed between studies. MSC-EVs were reported to activate multiple signaling pathways including mTOR/AKT, AMPK and BMP2. Subgroup analysis indicated no significant difference in the improvement of BV/TV when using modified EVs isolated after gene transfection, preconditioning (p = 0.61), or using EVs in combination with a tissue scaffold and/or hydrogel versus other delivery methods (p = 0.20).

conclusionUse of MSC-EVs to promote healing of bone injury appears promising, however, heterogeneity between studies and the potential for reporting bias limits confidence in the extent of benefit. Reducing bias between studies and addressing aspects of potential reporting bias should augment confidence in future meta-analyses and propel the field towards clinical studies. Forest Plot analysis assessing the percentage change in bone volume (BV) / total volume (TV) in the presence (experimental) or absence (control) of MSC-EVs.

Indexed as

Extracellular VesiclesMesenchymal Stem CellsAnimalsModels, AnimalBoneExosomesExtracellular vesiclesFractureMesenchymal stromal cellsMicrovesiclesRegenerationRepair

Identifiers

PMID34313927
OpenAlexW3185700649

What OpenQuestion holds

Textmetadata
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.