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Cited by 38Tendon Structure and TreatmentMesenchymal stem cell researchPeriodontal Regeneration and Treatments

Enhanced medial collateral ligament healing using mesenchymal stem cells: Dosage effects on cellular response and cytokine profile

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Saether, Erin E., Chamberlain, Connie S., Leiferman, Ellen M., Kondratko-Mittnacht, Jaclyn R., Li, Wan Ju, Brickson, Stacey L., Vanderby, Ray·2014·Stem Cell Reviews and Reports
DOI 10.1007/s12015-013-9479-7PMC PMC3946728
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Abstract

Mesenchymal stem cells (MSCs) have potential therapeutic applications for musculoskeletal injuries due to their ability to differentiate into several tissue cell types and modulate immune and inflammatory responses. These immune-modulatory properties were examined in vivo during early stage rat medial collateral ligament healing. Two different cell doses (low dose 1 × 10(6) or high dose 4 × 10(6) MSCs) were administered at the time of injury and compared with normal ligament healing at days 5 and 14 post-injury. At both times, the high dose MSC group demonstrated a significant decrease in M2 macrophages compared to controls. At day 14, fewer M1 macrophages were detected in the low dose group compared to the high dose group. These results, along with significant changes in procollagen I, proliferating cells, and endothelialization suggest that MSCs can alter the cellular response during healing in a dose-dependent manner. The higher dose ligaments also had increased expression of several pro-inflammatory cytokines at day 5 (IL-1β, IFNγ, IL-2) and increased expression of IL-12 at day 14. Mechanical testing at day 14 revealed increased failure strength and stiffness in low dose ligaments compared to controls. Based on these improved mechanical properties, MSCs enhanced functional healing when applied at a lower dose. Different doses of MSCs uniquely affected the cellular response and cytokine expression in healing ligaments. Interestingly, the lower dose of cells proved to be most effective in improving functional properties.

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  • In a rat model of MCL injury, the high-dose MSC group showed a significant decrease in M2 macrophages on days 5 and 14 postinjury and increased levels of several proinflammatory cytokines at day 5.

    “The high-dose group showed a significant decrease in M2 macrophages on days 5 and 14 postinjury and increased levels of several proinflammatory cytokines at day 5.”

    From Mesenchymal Stem Cells for Enhanced Healing of the Medial Collateral Ligament of the Knee Joint (2023) · cites this paper as [63]

  • In a rat model of MCL injury, mechanical tests demonstrated increased failure strength and stiffness in the low-dose MSC group on day 14.

    “In addition, mechanical tests demonstrated increased failure strength and stiffness in the low-dose group on day 14, suggesting that a lower dose of cells might be more effective in improving the functional properties of the injured MCL.”

    From Mesenchymal Stem Cells for Enhanced Healing of the Medial Collateral Ligament of the Knee Joint (2023) · cites this paper as [63]

  • In a rat model of MCL injury, the low-dose MSC group revealed fewer M1 macrophages than the high-dose group on day 14, implying the immunomodulatory ability of MSCs on cellular response during MCL healing in a dose-dependent manner.

    “The low-dose group revealed fewer M1 macrophages than the high-dose group on day 14, implying the immunomodulatory ability of MSCs on cellular response during MCL healing in a dose-dependent manner.”

    From Mesenchymal Stem Cells for Enhanced Healing of the Medial Collateral Ligament of the Knee Joint (2023) · cites this paper as [63]

  • A lower dose of MSCs might be more effective in improving the functional properties of the injured MCL.

    “In addition, mechanical tests demonstrated increased failure strength and stiffness in the low-dose group on day 14, suggesting that a lower dose of cells might be more effective in improving the functional properties of the injured MCL.”

    From Mesenchymal Stem Cells for Enhanced Healing of the Medial Collateral Ligament of the Knee Joint (2023) · cites this paper as [63]

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Research works printed but not linked: 33

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Authors
Saether, E. E., Chamberlain, C. S., Leiferman, E. M., Kondratko-Mittnacht, J. R., Li, W. J., Brickson, S. L., & Vanderby, R.
Affiliations
University of Wisconsin–Madison (US)
Corresponding author
Vanderby, Ray
ORCID
Venue
Stem Cell Reviews and Reports
Publisher
Springer Science and Business Media LLC
Published
2013-10-31
Volume
10
Issue
1
Pages
86-96
ISSN
  • 1550-8943 (ISSN-L)
  • 1558-6804
DOI
10.1007/s12015-013-9479-7
PMC
PMC3946728
OpenAlex
W1987119410
Cited by
38
References
37
Citations by year
2026: 5 · 2025: 1 · 2024: 1 · 2023: 3 · 2022: 4 · 2021: 5 · 2020: 2 · 2019: 4 · 2018: 2 · 2017: 1 · 2016: 4 · 2015: 5 · 2014: 1
FWCI
3.42
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Stem Cell Reviews and Reports (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR059916, AR059916)
Topics
  • Health Sciences › Medicine › Orthopedics and Sports Medicine › Tendon Structure and Treatment
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Health Sciences › Medicine › Urology › Periodontal Regeneration and Treatments
Keywords
mesenchymal stem cells, cell dose, M2 macrophages, M1 macrophages, inflammatory cytokines, IL-12, type I procollagen, endothelialization, ligament mechanical properties, ligament stiffness, rat model
MeSH terms
Animals, Cells, Cultured, Male, Wound Healing, Cytokines, Rats, Wistar, Medial Collateral Ligament, Knee, Mesenchymal Stem Cell Transplantation, Rats, Mesenchymal Stem Cells

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