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Evaluation of intra-articular mesenchymal stem cells to augment healing of microfractured chondral defects.

Abstract: This study evaluated intra-articular injection of bone marrow-derived mesenchymal stem cells (BMSCs) to augment healing with microfracture compared with microfracture alone. Methods: Ten horses (aged 2.5 to 5 years) had 1-cm2 defects arthroscopically created on both medial femoral condyles of the stifle joint (analogous to the human knee). Defects were debrided to subchondral bone followed by microfracture. One month later, 1 randomly selected medial femorotibial joint in each horse received an intra-articular injection of either 20 × 10(6) BMSCs with 22 mg of hyaluronan or 22 mg of hyaluronan alone. Horses were confined for 4 months, with hand walking commencing at 2 weeks and then increasing in duration and intensity. At 4 months, horses were subjected to strenuous treadmill exercise simulating race training until completion of the study at 12 months. Horses underwent musculoskeletal and radiographic examinations bimonthly and second-look arthroscopy at 6 months. Horses were euthanized 12 months after the defects were made, and the affected joints underwent magnetic resonance imaging and gross, histologic, histomorphometric, immunohistochemical, and biochemical examinations. Results: Although there was no evidence of any clinically significant improvement in the joints injected with BMSCs, arthroscopic and gross evaluation confirmed a significant increase in repair tissue firmness and a trend for better overall repair tissue quality (cumulative score of all arthroscopic and gross grading criteria) in BMSC-treated joints. Immunohistochemical analysis showed significantly greater levels of aggrecan in repair tissue treated with BMSC injection. There were no other significant treatment effects. Conclusions: Although there was no significant difference clinically or histologically in the 2 groups, this study confirms that intra-articular BMSCs enhance cartilage repair quality with increased aggrecan content and tissue firmness. Conclusions: Clinical use of BMSCs in conjunction with microfracture of cartilage defects may be potentially beneficial.
Publication Date: 2011-08-20 PubMed ID: 21862278DOI: 10.1016/j.arthro.2011.06.002Google Scholar: Lookup
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  • Comparative Study
  • Evaluation Study
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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This research evaluates the impact of using bone marrow-derived stem cells to assist in the healing process of microfractured bones, specifically in the knee, when compared to healing with microfracture alone. The results suggest that while there isn’t a significant clinical difference between the two groups, using stem cells does enhance the quality of cartilage repair, showing potential benefits for clinical use.

Research Methodology

  • The researchers conducted this experiment using ten horses. They created defects on both medial femoral condyles of the horse’s stifle joint (a structure similar to the human knee).
  • The defects were then cleaned and microfractured. After one month, one randomly chosen medial femorotibial joint in each horse was injected with either a combination of 20 × 10(6) bone marrow-derived mesenchymal stem cells (BMSCs) and 22 mg of hyaluronan, or 22 mg of hyaluronan alone.
  • Post-treatment, the horses were confined for 4 months, with a progressively increasing exercise regime starting two weeks post-injection. This included strenuous treadmill exercise designed to simulate race training up until the end of the study at 12 months.
  • Horses underwent clinical and radiographic examinations every two months and a second-look arthroscopy at 6 months.
  • The experimentation concluded at 12 months, with further analysis of the affected joints via magnetic resonance imaging and a variety of examinations including gross, histologic, histomorphometric, immunohistochemical, and biochemical analysis.

Findings

  • While there were no significant clinical improvements observed in the joints injected with BMSCs, the researchers noted a significant increase in the firmness of the repair tissue and a possible improvement in the overall repair tissue quality in these joints compared to those treated with hyaluronan alone.
  • Immunohistochemical analysis revealed significantly greater levels of aggrecan (a proteoglycan that plays an essential role in cartilage structure and function) in the repair tissue that was treated with BMSCs.
  • No other significant treatment effects were found by the researchers.

Conclusion

  • Although no clear clinical or histological differences were determined between the two groups, this study confirms that the use of intra-articular BMSCs can improve the quality of cartilage repair due to increased aggrecan content and tissue firmness.
  • The results of the study suggest that clinical use of BMSCs in conjunction with microfracture of cartilage defects could potentially be beneficial.

Cite This Article

APA
McIlwraith CW, Frisbie DD, Rodkey WG, Kisiday JD, Werpy NM, Kawcak CE, Steadman JR. (2011). Evaluation of intra-articular mesenchymal stem cells to augment healing of microfractured chondral defects. Arthroscopy, 27(11), 1552-1561. https://doi.org/10.1016/j.arthro.2011.06.002

Publication

ISSN: 1526-3231
NlmUniqueID: 8506498
Country: United States
Language: English
Volume: 27
Issue: 11
Pages: 1552-1561

Researcher Affiliations

McIlwraith, C Wayne
  • Orthopaedic Research Center, Colorado State University, Fort Collins, Colorado 80523, USA.
Frisbie, David D
    Rodkey, William G
      Kisiday, John D
        Werpy, Natasha M
          Kawcak, Christopher E
            Steadman, J Richard

              MeSH Terms

              • Animals
              • Arthroplasty, Subchondral
              • Arthroscopy
              • Bone Marrow Transplantation
              • Cartilage / injuries
              • Cartilage / pathology
              • Cartilage / physiology
              • Cartilage / surgery
              • Combined Modality Therapy
              • Horses
              • Hyaluronic Acid / therapeutic use
              • Injections, Intra-Articular
              • Intra-Articular Fractures
              • Knee Injuries / diagnostic imaging
              • Knee Injuries / pathology
              • Knee Injuries / surgery
              • Magnetic Resonance Imaging
              • Mesenchymal Stem Cell Transplantation
              • Models, Animal
              • Orthopedic Procedures / methods
              • Radiography
              • Random Allocation
              • Single-Blind Method
              • Stifle / injuries
              • Stifle / physiology
              • Synovial Membrane / pathology
              • Treatment Outcome
              • Viscosupplements / therapeutic use
              • Wound Healing

              Citations

              This article has been cited 95 times.