Osteochondral regeneration of the femoral medial condyle by using a scaffold-free 3D construct of synovial membrane-derived mesenchymal stem cells in horses.
Abstract: Medical interventions for subchondral bone cysts in horses have been extensively studied. This study investigated the regeneration of articular cartilage and subchondral bone with scaffold-free three-dimensional (3D) constructs of equine synovial membrane-derived mesenchymal stem cells (SM-MSCs) isolated from three ponies and expanded until over 1.0 × 10 cells at passage 2 (P2). Results: SM-MSCs were strongly positive for CD11a/CD18, CD44, and major histocompatibility complex (MHC) class I; moderately positive for CD90, CD105, and MHC class II; and negative for CD34 and CD45 on flow cytometry and differentiated into osteogenic, chondrogenic, and adipogenic lineages in the tri-lineage differentiation assay. After culturing SM-MSCs until P3, we prepared a construct (diameter, 6.3 mm; height, 5.0 mm) comprising approximately 1920 spheroids containing 3.0 × 10 cells each. This construct was confirmed to be positive for type I collagen and negative for type II collagen, Alcian blue, and Safranin-O upon histological analysis and was subsequently implanted into an osteochondral defect (diameter, 6.8 mm; depth, 5.0 mm) at the right femoral medial condyle. The contralateral (left femoral) defect served as the control. At 3 and 6 months after surgery, the radiolucent volume (RV, mm) of the defects was calculated based on multiplanar reconstruction of computed tomography (CT) images. Magnetic resonance (MR) images were evaluated using a modified two-dimensional MR observation of cartilage repair tissue (MOCART) grading system, while macroscopic (gross) and microscopic histological characteristics were scored according to the International Cartilage Repair Society (ICRS) scale. Compared to the control sites, the implanted defects showed lower RV percentages, better total MOCART scores, higher average gross scores, and higher average histological scores. Conclusions: Implantation of a scaffold-free 3D-construct of SM-MSCs into an osteochondral defect could regenerate the original structure of the cartilage and subchondral bone over 6 months post-surgery in horses, indicating the potential of this technique in treating equine subchondral bone cysts.
© 2022. The Author(s).
Publication Date: 2022-01-22 PubMed ID: 35065631PubMed Central: PMC8783486DOI: 10.1186/s12917-021-03126-yGoogle Scholar: Lookup
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- Journal Article
- Articular Cartilage
- Cell Culture
- Clinical Study
- Computed Tomography
- Disease Treatment
- Equine Diseases
- Equine Health
- Flow Cytometry
- Horses
- In Vivo
- Magnetic Resonance Imaging
- Major Histocompatibility Complex (MHC)
- Mesenchymal Cells
- Orthopedics
- Radiology
- Regeneration
- Stem Cells
- Subchondral Bone
- Surgery
- Veterinary Medicine
Summary
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The research investigates the regeneration of joint cartilage and underlying bone in horses, using a scaffold-free 3D structure of equine synovial membrane-derived mesenchymal stem cells. The study demonstrated that this technique could restore the original structure of the cartilage and bone over a six-month post-surgical period, which opens up a potential treatment for equine subchondral bone cysts.
Study Design
- The study used mesenchymal stem cells (SM-MSCs) derived from the synovial membranes of three ponies. These cells were expanded until they reached a significant count.
- These SM-MSCs were confirmed to express certain cell surface markers and have the capacity to differentiate into bone, cartilage, and fat cell lineages.
- A scaffold-free 3D construct was prepared using these stem cells. This construct was confirmed to express type I collagen, which is a major component of the extracellular matrix in various tissues.
- This structure was then implanted into an osteochondral defect (a joint injury affecting both the cartilage and underlying bone) in the right femoral medial condyle of the horse. The equivalent defect on the left side was left untreated to serve as a control.
Measurements and Results
- The treatment’s effect was assessed at 3 and 6 months post-surgery through a variety of methods. This included computed tomography (CT) scans, magnetic resonance (MR) imaging, and both macroscopic (visible to the naked eye) and microscopic (requiring magnification) inspection of the tissue.
- The CT images allowed for the calculation of the volume of the defects, whilst the MR images were evaluated using a specific grading system for cartilage repair assessment.
- The overall assessment demonstrated that the treated defects showed lower radiolucent volume (indicating denser tissue), better cartilage repair scores, and higher average histological scores when compared to the control sites.
Conclusion
- The results of this study signify the potential of using a scaffold-free 3D construct of SM-MSCs to regenerate osteochondral defects in horses.
- This technique could possibly serve as a treatment approach for equine subchondral bone cysts – fluid-filled holes in the subchondral bone under the joint cartilage. This disorder is common in horses and can lead to persistent lameness and potentially end a horse’s competitive career.
Cite This Article
APA
Murata D, Ishikawa S, Sunaga T, Saito Y, Sogawa T, Nakayama K, Hobo S, Hatazoe T.
(2022).
Osteochondral regeneration of the femoral medial condyle by using a scaffold-free 3D construct of synovial membrane-derived mesenchymal stem cells in horses.
BMC Vet Res, 18(1), 53.
https://doi.org/10.1186/s12917-021-03126-y Publication
Researcher Affiliations
- Department of Veterinary Clinical Science, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima, Japan. daiki_net_official@yahoo.co.jp.
- Department of Regenerative Medicine and Biomedical Engineering, Center for Regenerative Medicine Research, Faculty of Medicine, Saga University, Saga, Japan. daiki_net_official@yahoo.co.jp.
- Department of Veterinary Clinical Science, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima, Japan.
- Division of Veterinary Science, Graduate School of Life and Environmental Biosciences, Osaka Prefecture University, Izumi-Sano, Japan.
- Veterinary Teaching Hospital, Faculty of Veterinary Medicine, Kagoshima University, Kagoshima, Japan.
- Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
- Veterinary Teaching Hospital, Faculty of Veterinary Medicine, Kagoshima University, Kagoshima, Japan.
- Veterinary Teaching Hospital, Faculty of Veterinary Medicine, Kagoshima University, Kagoshima, Japan.
- Department of Regenerative Medicine and Biomedical Engineering, Center for Regenerative Medicine Research, Faculty of Medicine, Saga University, Saga, Japan.
- Department of Veterinary Clinical Science, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima, Japan.
- Department of Veterinary Clinical Science, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima, Japan.
MeSH Terms
- Animals
- Bone Cysts / veterinary
- Cartilage, Articular
- Femur
- Horse Diseases
- Horses
- Mesenchymal Stem Cells
- Regeneration
- Synovial Membrane / cytology
- Tissue Scaffolds
Conflict of Interest Statement
Koichi Nakayama is a co-founder and shareholder of Cyfuse Biomedical KK. The other authors do not declare any conflict of interest.
References
This article includes 30 references
Citations
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