Evidence map›Paper›PMID 32924528›Full record

ArticleThe American journal of sports medicine2020

A Translational Porcine Model for Human Cell-Based Therapies in the Treatment of Posttraumatic Osteoarthritis After Anterior Cruciate Ligament Injury.

Thomas J Kremen, Tina Stefanovic, Wafa Tawackoli, Khosrowdad Salehi, Pablo Avalos, Derek Reichel, Manuel J Perez, Juliane D Glaeser, Dmitriy Sheyn

Erratum issuedOpen access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The American journal of sports medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.8field-weighted citation impact, top 14% 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

8 citing papers in PubMed, 16 citations in OpenAlex.

  1. Review
  2. Article
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  4. Preclinical tendon and ligament models: Beyond the 3Rs (replacement, reduction, and refinement) to 5W1H (why, who, what, where, when, how).Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2023
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Thomas J KremenDepartment of Orthopaedic Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Tina StefanovicOrthopaedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Wafa TawackoliOrthopaedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Khosrowdad SalehiOrthopaedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Pablo AvalosBoard of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Derek ReichelBiomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Manuel J PerezBiomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Juliane D GlaeserOrthopaedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Dmitriy SheynOrthopaedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Cedars-Sinai Medical Center · USUniversity of California, Los Angeles · US

Funding

Induced pluripotent stem cell therapy for degenerated IVDK01AR071512 · NIAMS · CEDARS-SINAI MEDICAL CENTER · PI SHEYN, DMITRIY · 2018 to 2022
$595k
NIAMS NIH HHS K01 AR071512
6 · The paper itself

Abstract

backgroundThere is a high incidence of posttraumatic osteoarthritis (PTOA) after anterior cruciate ligament (ACL) injury, and these injuries represent an enormous health care economic burden. In an effort to address this unmet clinical need, there has been increasing interest in cell-based therapies. PURPOSE: To establish a translational large animal model of PTOA and demonstrate the feasibility of intra-articular human cell-based interventions. STUDY

designDescriptive laboratory study.

methodsNine Yucatan mini-pigs underwent unilateral ACL transection and were monitored for up to 12 weeks after injury. Interleukin 1 beta (IL-1β) levels and collagen breakdown were evaluated longitudinally using enzyme-linked immunosorbent assays of synovial fluid, serum, and urine. Animals were euthanized at 4 weeks (n = 3) or 12 weeks (n = 3) after injury, and injured and uninjured limbs underwent magnetic resonance imaging (MRI) and histologic analysis. At 2 days after ACL injury, an additional 3 animals received an intra-articular injection of 10

resultsPTOA was detected as early as 4 weeks after injury. At 12 weeks after injury, osteoarthritis could be detected grossly as well as on histologic analysis. Synovial fluid analysis showed elevation of IL-1β shortly after ACL injury, with subsequent resolution by 2 weeks after injury. Collagen type II protein fragments were elevated in the synovial fluid and serum after injury. hBM-MSCs-Luc were detected immediately after injection and at 2 weeks after injection using fluorescence imaging, MRI, and bioluminescence imaging.

conclusionThis study demonstrates the feasibility of reproducing the chondral changes, intra-articular cytokine alterations, and body fluid biomarker findings consistent with PTOA after ACL injury in a large animal model. Furthermore, we have demonstrated the ability of hBM-MSCs to survive and express transgene within the knee joint of porcine hosts without immunosuppression for at least 2 weeks. CLINICAL RELEVANCE: This model holds great potential to significantly contribute to investigations focused on the development of cell-based therapies for human ACL injury-associated PTOA in the future (see Appendix Figure A1, available online).

Indexed as

Cartilage, ArticularMesenchymal Stem Cell TransplantationAnimalsAnterior Cruciate Ligament InjuriesBiomarkersCytokinesDisease Models, AnimalHumansKnee JointOsteoarthritisSwineSwine, MiniatureSynovial FluidBiomarkersCytokinesACLbiology of cartilageknee articular cartilageposttraumatic osteoarthritisstem cell therapy

Identifiers

PMID32924528
PMCPMC7945314
OpenAlexW3086291086

What OpenQuestion holds

Textmetadata
LicenceTDM
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.