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FASEB journal : official publication of the Federation of American Societies for Experimental Biology2019; 33(12); 14337-14353; doi: 10.1096/fj.201901684RR

Autologous bone marrow mononuclear cells modulate joint homeostasis in an equine in vivo model of synovitis.

Abstract: Osteoarthritis (OA) is characterized by macrophage-driven synovitis. Macrophages promote synovial health but become inflammatory when their regulatory functions are overwhelmed. Bone marrow mononuclear cells (BMNCs) are a rich source of macrophage progenitors used for treating chronic inflammation and produce essential molecules for cartilage metabolism. This study investigated the response to autologous BMNC injection in normal and inflamed joints. Synovitis was induced in both radiocarpal joints of 6 horses. After 8 h, 1 inflamed radiocarpal and 1 normal tarsocrural joint received BMNC injection. Contralateral joints were injected with saline. Synovial fluid was collected at 24, 96, and 144 h for cytology, cytokine quantification, and flow cytometry. At 144 h, horses were euthanatized, joints were evaluated, and synovium was harvested for histology and immunohistochemistry. Four days after BMNC treatment, inflamed joints had 24% higher macrophage counts with 10% more IL-10 cells than saline-treated controls. BMNC-treated joints showed gross and analytical improvements in synovial fluid and synovial membrane, with increasing regulatory macrophages and synovial fluid IL-10 concentrations compared with saline-treated controls. BMNC-treated joints were comparable to healthy joints histologically, which remained abnormal in saline-treated controls. Autologous BMNCs are readily available, regulate synovitis through macrophage-associated effects, and can benefit thousands of patients with OA.-Menarim, B. C., Gillis, K. H., Oliver, A., Mason, C., Ngo, Y., Werre, S. R., Barrett, S. H., Luo, X., Byron, C. R., Dahlgren, L. A. Autologous bone marrow mononuclear cells modulate joint homeostasis in an equine model of synovitis.
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Publication Date: 2019-10-30 PubMed ID: 31665925DOI: 10.1096/fj.201901684RRGoogle Scholar: Lookup
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  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research investigates how autologous bone marrow mononuclear cells (BMNCs), a rich source of macrophage progenitors, can help in treating osteoarthritis by regulating synovitis. The study showed that the injection of BMNCs in both normal and inflamed joints of horses resulted in the improvement of synovial fluid and histological comparisons to healthy joints.

Research Objective

The main objective of this research was to examine the effects of bone marrow mononuclear cells (BMNCs) on synovitis – inflammation of the joint lining, often occurring in osteoarthritis (OA) patients. Specifically, the study aimed to investigate:

  • How autologous BMNC injection would affect normal and inflamed joints
  • The role of BMNCs in joint homeostasis regulation

Methodology

The study was conducted on six horses where synovitis was artificially induced in both their radiocarpal joints – equivalent to the human wrist. Post eight hours, one of the inflamed joints, along with a normal tarsocrural joint – equivalent to the human ankle, was injected with autologous BMNCs. For comparison, the remaining joints were injected with saline. Synovial fluid was collected at multiple time points for further analysis, which included cytology, cytokine quantification, and flow cytometry. Finally, the horses were euthanized to allow the joints to be evaluated in depth, with the synovium – a thin layer of tissue lining the joints/spaces that secrete synovial fluid – harvested for histology and immunohistochemistry.

Findings

The results showed that four days after BMNC treatment, the inflamed joints had a 24% higher macrophage count, with a 10% increase in interleukin-10 (IL-10) cells compared to the saline control group. The macrophages, derived from the injected BMNCs, were presumably helping to regulate the inflammation. BMNC-treated joints illustrated visible and analytical enhancements both in the synovial fluid and synovial membrane, with increased regulatory macrophages and increased synovial fluid IL-10 concentrations, compared to the saline-treated controls. Histologically, the BMNC-treated joints were similar to healthy joints, in contrast to the saline-treated joints, suggesting BMNCs can help restore joint health.

Conclusion

The study concludes that BMNCs, which are easily available, can potentially manage synovitis through effects related to macrophages. These findings are crucial in advancing potential treatment options for OA, a common and debilitating condition. The use of BMNCs has the potential to benefit thousands of patients afflicted with osteoarthritis.

Cite This Article

APA
Menarim BC, Gillis KH, Oliver A, Mason C, Ngo Y, Werre SR, Barrett SH, Luo X, Byron CR, Dahlgren LA. (2019). Autologous bone marrow mononuclear cells modulate joint homeostasis in an equine in vivo model of synovitis. FASEB J, 33(12), 14337-14353. https://doi.org/10.1096/fj.201901684RR

Publication

FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
NlmUniqueID: 8804484
Country: United States
Language: English
Volume: 33
Issue: 12
Pages: 14337-14353

Researcher Affiliations

Menarim, Bruno C
  • Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA.
Gillis, Kiersten H
  • Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA.
Oliver, Andrea
  • Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA.
Mason, Caitlin
  • Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA.
Ngo, Ying
  • Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA.
Werre, Stephen R
  • Laboratory for Study Design and Statistical Analysis, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA.
Barrett, Sarah H
  • Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA.
Luo, Xin
  • Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA.
Byron, Christopher R
  • Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA.
Dahlgren, Linda A
  • Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA.

MeSH Terms

  • Animals
  • Bone Marrow Cells
  • Bone Marrow Transplantation
  • Female
  • Hematopoietic Stem Cell Transplantation / veterinary
  • Hematopoietic Stem Cells / physiology
  • Horse Diseases / therapy
  • Horses
  • Injections, Intra-Articular
  • Joints / metabolism
  • Joints / pathology
  • Leukocytes, Mononuclear
  • Male
  • Synovitis / therapy
  • Synovitis / veterinary

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Citations

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