Evidence map›Paper›PMID 40461558›Full record

ArticleNPJ Regenerative medicine2025

Engineered BMP2/BMP7 extracellular vesicles induce autocrine BMP release driving SMAD phosphorylation to promote bone formation.

Zeji Du, Skylar A Rizzo, Tiffany L Sarrafian, Monique S Bagwell, Ryan C Mahlberg, Ashley Amontree, Paige Schiebel, Dinah M Tauferner, Zoe S LeBrasseur, Tyra A Witt and 8 more

Abstract read
In one paragraph

Article in NPJ Regenerative medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
–field-weighted citation impact
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

13 citing papers in PubMed.

  1. Extracellular Vesicles and Their Role in Osteogenesis.Bioengineering (Basel, Switzerland) · 2026
    Review
  2. Article
  3. Review
  4. Review
  5. Article
  6. Review
  7. Review
  8. Bone matrix proteins: regulators of skeletal remodeling and repair.Journal of bone and mineral metabolism · 2026
    Review
  9. Review
  10. Article
  11. Review
  12. Review
  13. 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

18 authors.

Zeji Du *Van Cleve Cardiac Regenerative Medicine Program, Mayo Clinic Center for Regenerative Medicine, Rochester, MN, USA.
Skylar A Rizzo *Van Cleve Cardiac Regenerative Medicine Program, Mayo Clinic Center for Regenerative Medicine, Rochester, MN, USA.
Tiffany L SarrafianVan Cleve Cardiac Regenerative Medicine Program, Mayo Clinic Center for Regenerative Medicine, Rochester, MN, USA.
Monique S BagwellVan Cleve Cardiac Regenerative Medicine Program, Mayo Clinic Center for Regenerative Medicine, Rochester, MN, USA.ORCID http://orcid.org/0000-0003-4971-1180
Ryan C MahlbergVan Cleve Cardiac Regenerative Medicine Program, Mayo Clinic Center for Regenerative Medicine, Rochester, MN, USA.
Ashley AmontreeVan Cleve Cardiac Regenerative Medicine Program, Mayo Clinic Center for Regenerative Medicine, Rochester, MN, USA.
Paige SchiebelVan Cleve Cardiac Regenerative Medicine Program, Mayo Clinic Center for Regenerative Medicine, Rochester, MN, USA.
Dinah M TaufernerVan Cleve Cardiac Regenerative Medicine Program, Mayo Clinic Center for Regenerative Medicine, Rochester, MN, USA.
Zoe S LeBrasseurVan Cleve Cardiac Regenerative Medicine Program, Mayo Clinic Center for Regenerative Medicine, Rochester, MN, USA.
Tyra A WittVan Cleve Cardiac Regenerative Medicine Program, Mayo Clinic Center for Regenerative Medicine, Rochester, MN, USA.
Mary NagelVan Cleve Cardiac Regenerative Medicine Program, Mayo Clinic Center for Regenerative Medicine, Rochester, MN, USA.
Kyla A BoydMayo Clinic Department of Virology and Gene Therapy, Mayo Clinic, Rochester, MN, USA.ORCID http://orcid.org/0000-0002-5750-3624
Humberto De VittoVan Cleve Cardiac Regenerative Medicine Program, Mayo Clinic Center for Regenerative Medicine, Rochester, MN, USA.
Matthew L HillestadVan Cleve Cardiac Regenerative Medicine Program, Mayo Clinic Center for Regenerative Medicine, Rochester, MN, USA.
Paul G StalboergerVan Cleve Cardiac Regenerative Medicine Program, Mayo Clinic Center for Regenerative Medicine, Rochester, MN, USA.
Matthew T HoudekMayo Clinic Department of Orthopedic Medicine, Rochester, MN, USA.ORCID http://orcid.org/0000-0003-0390-1018
Rafael J SierraMayo Clinic Department of Orthopedic Medicine, Rochester, MN, USA.
Atta BehfarVan Cleve Cardiac Regenerative Medicine Program, Mayo Clinic Center for Regenerative Medicine, Rochester, MN, USA. behfar.atta@mayo.edu.

Funding

PhD Training Program in Virology and Gene TherapyT32AI132165 · NIAID · MAYO CLINIC ROCHESTER · PI ROBERTO B. CATTANEO · 2018 to 2026
$1.3M
NIAID NIH HHS T32 AI132165
6 · The paper itself

Abstract

In the United States, impaired bone healing impacts ~600,000 patients annually. Bone morphogenetic protein 2 (rhBMP2) therapy is impeded by low bone quality and adverse effects. Here, mesenchymal stem cells, engineered to produce BMP2 and BMP2/7 containing extracellular vesicles (BMP2-EV and BMP2/7-EV), provided an alternative means of stimulating bone formation. BMP2-EV and BMP2/7-EV drove increased calcium deposition and alkaline phosphatase activity; with increase in osterix, RUNX2, osteocalcin, and osteopontin documenting osteoblast differentiation. BMP2/7-EV induced SMAD phosphorylation and calcium deposition, was inhibited by DMH1, a BMP I receptor inhibitor, demonstrating BMP receptor dependence. BMP2 and BMP7 extracellular vesicle encapsulation was confirmed with preserved potency following treatment with BMP antagonist, Noggin. Application of BMP2/7-EV in a rat calvarial defect model demonstrated enhanced bone formation on micro-computed tomography and histopathologic analysis, equaling rhBMP2. BMP2/7-EV mediated bone formation here highlights EVs as a unique modality for delivery of tailored polyvalent regenerative biotherapies.

Identifiers

PMID40461558
PMCPMC12134205

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.