Inflammation affects the viability and plasticity of equine mesenchymal stem cells: possible implications in intra-articular treatments.
Abstract: Mesenchymal stem cells (MSCs) are gaining relevance for treating equine joint injuries because of their ability to limit inflammation and stimulate regeneration. Because inflammation activates MSC immunoregulatory function, proinflammatory priming could improve MSC efficacy. However, inflammatory molecules present in synovial fluid or added to the culture medium might have deleterious effects on MSCs. Therefore, this study was conducted to investigate the effects of inflammatory synovial fluid and proinflammatory cytokines priming on viability and plasticity of equine MSCs. Equine bone marrow derived MSCs (eBM-MSCs) from three animals were cultured for 72 h in media supplemented with: 20% inflammatory synovial fluid (SF); 50 ng/mL IFN-γ and TNF-α (CK50); and 20 ng/mL IFN-γ and TNF-α (CK20). Proliferation assay and expression of proliferation and apoptosis-related genes showed that SF exposed-eBM-MSCs maintained their viability, whereas the viability of CK primed-eBM-MSCs was significantly impaired. Tri-lineage differentiation assay revealed that exposure to inflammatory synovial fluid did not alter eBM-MSCs differentiation potential; however, eBM-MSCs primed with cytokines did not display osteogenic, adipogenic or chondrogenic phenotype. The inflammatory synovial environment is well tolerated by eBM-MSCs, whereas cytokine priming negatively affects the viability and differentiation abilities of eBM-MSCs, which might limit their in vivo efficacy.
Publication Date: 2016-06-15 PubMed ID: 27297420PubMed Central: PMC5366301DOI: 10.4142/jvs.2017.18.1.39Google Scholar: Lookup
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- Journal Article
Summary
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This study explores how inflammation affects the survival and the ability of equine mesenchymal stem cells (MSCs) to change, with a focus on the implications for treatments inside the joints. The research found that an inflammatory joint environment is tolerable for equine MSCs, but priming with inflammatory substances can harm these stem cells, potentially limiting their effectiveness in treatment.
Introduction
- The research focuses on understanding the impact of inflammation on equine Mesenchymal Stem Cells (MSCs). MSCs are important in treating joint injuries in horses due to their ability to control inflammation and stimulate tissue regeneration.
- The role of inflammation is paradoxical. On one hand, it is known to trigger the immunoregulatory function of MSCs, suggesting that ‘priming’ the cells with proinflammatory substances might enhance their therapeutic efficacy. On the other hand, inflammatory substances in the joint fluid or those added to the cells’ culture environment might be harmful to the MSCs. This forms the crux of the research problem.
Methodology
- The study used equine MSCs sourced from bone marrow (eBM-MSCs) and cultured them for 72 hours in different conditions to assess how MSC behavior is affected.
- Some MSCs were exposed to 20% inflammatory synovial fluid (SF), while others were primed with 50 ng/mL or 20 ng/mL of two pro-inflammatory cytokines (IFN-γ and TNF-α, labelled as CK50 and CK20 respectively).
- The researchers conducted cell proliferation assays and gene expression studies to evaluate the impact on cell viability. They also carried out differentiation assays to check the ability of MSCs to transform into different cell types – a crucial aspect of their regeneration-promoting function.
Findings
- The research found that MSCs exposed to the inflammatory SF maintained their viability, indicating that they can survive in an inflamed joint environment.
- However, MSCs primed with cytokines (both CK50 and CK20) showed significantly reduced viability – a finding that challenges the idea that proinflammatory priming could enhance MSC efficacy in treating inflammatory joint problems.
- While SF exposure did not alter the MSCs’ ability to differentiate into multiple lineages, the cytokines-primed MSCs failed to show osteogenic, adipogenic, or chondrogenic phenotype – severely undermining their potential therapeutic value for joint injuries.
Implication
- The study suggests that while MSCs can survive in an inflamed joint microenvironment, the use of proinflammatory priming with cytokines might have a detrimental effect on their survival and therapeutic potential. This impacts the approach to MSC-based therapy for equine joint injuries.
Cite This Article
APA
Barrachina L, Remacha AR, Romero A, Vázquez FJ, Albareda J, Prades M, Ranera B, Zaragoza P, Martín-Burriel I, Rodellar C.
(2016).
Inflammation affects the viability and plasticity of equine mesenchymal stem cells: possible implications in intra-articular treatments.
J Vet Sci, 18(1), 39-49.
https://doi.org/10.4142/jvs.2017.18.1.39 Publication
Researcher Affiliations
- Laboratory of Biochemical Genetics LAGENBIO, Veterinary Hospital, University of Zaragoza, 50013 Zaragoza, Spain.
- Service of Equine Surgery and Medicine, Veterinary Hospital, University of Zaragoza, 50013 Zaragoza, Spain.
- Laboratory of Biochemical Genetics LAGENBIO, Veterinary Hospital, University of Zaragoza, 50013 Zaragoza, Spain.
- Laboratory of Biochemical Genetics LAGENBIO, Veterinary Hospital, University of Zaragoza, 50013 Zaragoza, Spain.
- Service of Equine Surgery and Medicine, Veterinary Hospital, University of Zaragoza, 50013 Zaragoza, Spain.
- Laboratory of Biochemical Genetics LAGENBIO, Veterinary Hospital, University of Zaragoza, 50013 Zaragoza, Spain.
- Service of Equine Surgery and Medicine, Veterinary Hospital, University of Zaragoza, 50013 Zaragoza, Spain.
- Laboratory of Biochemical Genetics LAGENBIO, Veterinary Hospital, University of Zaragoza, 50013 Zaragoza, Spain.
- Service of Orthopedic Surgery and Traumatology, University Clinical Hospital Lozano Blesa, 50009 Zaragoza, Spain.
- Laboratory of Biochemical Genetics LAGENBIO, Veterinary Hospital, University of Zaragoza, 50013 Zaragoza, Spain.
- Service of Equine Surgery, Veterinary Hospital, Autonomous University of Barcelona, 08193 Barcelona, Spain.
- Laboratory of Biochemical Genetics LAGENBIO, Veterinary Hospital, University of Zaragoza, 50013 Zaragoza, Spain.
- Laboratory of Biochemical Genetics LAGENBIO, Veterinary Hospital, University of Zaragoza, 50013 Zaragoza, Spain.
- Laboratory of Biochemical Genetics LAGENBIO, Veterinary Hospital, University of Zaragoza, 50013 Zaragoza, Spain.
- Laboratory of Biochemical Genetics LAGENBIO, Veterinary Hospital, University of Zaragoza, 50013 Zaragoza, Spain.
MeSH Terms
- Animals
- Horse Diseases / immunology
- Horse Diseases / metabolism
- Horses
- Inflammation / immunology
- Inflammation / metabolism
- Inflammation / veterinary
- Injections, Intra-Articular / veterinary
- Interferon-gamma / metabolism
- Male
- Mesenchymal Stem Cells / cytology
- Synovial Fluid / cytology
- Tumor Necrosis Factor-alpha / metabolism
Conflict of Interest Statement
Conflict of Interest: The authors declare no conflict of interest.
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