Evidence map›Paper›PMID 29784586›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2018

Ultrasound-Mediated Gene Delivery Enhances Tendon Allograft Integration in Mini-Pig Ligament Reconstruction.

Maxim Bez, Thomas J Kremen, Wafa Tawackoli, Pablo Avalos, Dmitriy Sheyn, Galina Shapiro, Joseph C Giaconi, Shiran Ben David, Jess G Snedeker, Zulma Gazit and 3 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
4.3field-weighted citation impact, top 6% 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

17 citing papers in PubMed, 39 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Advanced Gene Therapy Strategies for the Repair of ACL Injuries.International journal of molecular sciences · 2022
    Review
  5. Article
  6. Review
  7. Review
  8. Article
  9. Recent Advances in Stimulus-Responsive Nanocarriers for Gene Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021
    Review
  10. Article
  11. Article
  12. Review
  13. Low-frequency ultrasound-mediated cytokine transfection enhances T cell recruitment at local and distant tumor sites.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  14. Article
  15. Article
  16. Article
  17. 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

13 authors at 4 institutions in 3 countries.

Maxim BezSkeletal Biotech Laboratory, The Hebrew University-Hadassah Faculty of Dental Medicine, Ein Kerem, Jerusalem 91120, Israel; Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Thomas J KremenDepartment of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Orthopedics, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Wafa TawackoliDepartment of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Pablo AvalosBoard of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Dmitriy SheynDepartment of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Galina ShapiroSkeletal Biotech Laboratory, The Hebrew University-Hadassah Faculty of Dental Medicine, Ein Kerem, Jerusalem 91120, Israel.
Joseph C GiaconiDepartment of Imaging, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Shiran Ben DavidDepartment of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Jess G SnedekerDepartment of Orthopedics, University of Zurich, Zurich 8008, Switzerland.
Zulma GazitSkeletal Biotech Laboratory, The Hebrew University-Hadassah Faculty of Dental Medicine, Ein Kerem, Jerusalem 91120, Israel; Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Orthopedics, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Katherine W FerraraDepartment of Biomedical Engineering, University of California, Davis, Davis, CA 95616, USA.
Dan GazitSkeletal Biotech Laboratory, The Hebrew University-Hadassah Faculty of Dental Medicine, Ein Kerem, Jerusalem 91120, Israel; Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Orthopedics, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Gadi PelledSkeletal Biotech Laboratory, The Hebrew University-Hadassah Faculty of Dental Medicine, Ein Kerem, Jerusalem 91120, Israel; Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. Electronic address: gadi.pelled@cshs.org.
Cedars-Sinai Medical Center · USHebrew University of Jerusalem · ILUniversity of California, Davis · USUniversity of Zurich · CH

Funding

UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1M
UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
Specific and high-resolution ultrasound cancer imagingR01CA112356 · NCI · UNIVERSITY OF CALIFORNIA DAVIS · PI FERRARA, KATHERINE W, FOIRET, JOSQUIN · 2005 to 2022
$6.1M
NCATS NIH HHS UL1 TR000124NCATS NIH HHS UL1 TR001881NCI NIH HHS R01 CA112356
6 · The paper itself

Abstract

Ligament injuries occur frequently, substantially hindering routine daily activities and sports participation in patients. Surgical reconstruction using autogenous or allogeneic tissues is the gold standard treatment for ligament injuries. Although surgeons routinely perform ligament reconstructions, the integrity of these reconstructions largely depends on adequate biological healing of the interface between the ligament graft and the bone. We hypothesized that localized ultrasound-mediated, microbubble-enhanced therapeutic gene delivery to endogenous stem cells would lead to significantly improved ligament graft integration. To test this hypothesis, an anterior cruciate ligament reconstruction procedure was performed in Yucatan mini-pigs. A collagen scaffold was implanted in the reconstruction sites to facilitate recruitment of endogenous mesenchymal stem cells. Ultrasound-mediated reporter gene delivery successfully transfected 40% of cells recruited to the reconstruction sites. When BMP-6 encoding DNA was delivered, BMP-6 expression in the reconstruction sites was significantly enhanced. Micro-computed tomography and biomechanical analyses showed that ultrasound-mediated BMP-6 gene delivery led to significantly enhanced osteointegration in all animals 8 weeks after surgery. Collectively, these findings demonstrate that ultrasound-mediated gene delivery to endogenous mesenchymal progenitor cells can effectively improve ligament reconstruction in large animals, thereby addressing a major unmet orthopedic need and offering new possibilities for translation to the clinical setting.

Indexed as

AllograftsAnimalsAnterior Cruciate Ligament ReconstructionBone Morphogenetic Protein 6CollagenGene Transfer TechniquesLigamentsMesenchymal Stem CellsMesenchymal Stem Cell TransplantationStem CellsSwineSwine, MiniatureTendonsTransplantation, HomologousUltrasonographyX-Ray MicrotomographyBone Morphogenetic Protein 6Collagengene therapyregenerative medicinetissue engineering

Identifiers

PMID29784586
PMCPMC6035740
OpenAlexW2802184214

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.