Mesenchymal Stromal Cells Adapt to Chronic Tendon Disease Environment with an Initial Reduction in Matrix Remodeling.
Abstract: Tendon lesions are common sporting injuries in humans and horses alike. The healing process of acute tendon lesions frequently results in fibrosis and chronic disease. In horses, local mesenchymal stromal cell (MSC) injection is an accepted therapeutic strategy with positive influence on acute lesions. Concerning the use of MSCs in chronic tendon disease, data are scarce but suggest less therapeutic benefit. However, it has been shown that MSCs can have a positive effect on fibrotic tissue. Therefore, we aimed to elucidate the interplay of MSCs and healthy or chronically diseased tendon matrix. Equine MSCs were cultured either as cell aggregates or on scaffolds from healthy or diseased equine tendons. Higher expression of tendon-related matrix genes and tissue inhibitors of metalloproteinases (TIMPs) was found in aggregate cultures. However, the tenogenic transcription factor scleraxis was upregulated on healthy and diseased tendon scaffolds. Matrix metalloproteinase (MMPs) expression and activity were highest in healthy scaffold cultures but showed a strong transient decrease in diseased scaffold cultures. The release of glycosaminoglycan and collagen was also higher in scaffold cultures, even more so in those with tendon disease. This study points to an early suppression of MSC matrix remodeling activity by diseased tendon matrix, while tenogenic differentiation remained unaffected.
Publication Date: 2021-11-26 PubMed ID: 34884602PubMed Central: PMC8657831DOI: 10.3390/ijms222312798Google Scholar: Lookup
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- Journal Article
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 article explores how mesenchymal stromal cells (MSCs), used as a treatment strategy due to its positive influence on acute lesions, interact with the environment of chronic tendon disease. Findings suggest that the matrix remodeling process is initially suppressed in MSCs within a diseased tendon matrix, while tenogenic differentiation is unaffected.
Objective of the Research
- The main objective of the research was to understand how Mesenchymal Stromal Cells (MSCs) behave within the environment of chronic tendon disease – a condition commonly seen in athletes and horses, often resulting in fibrosis.
- The researchers aimed to explain the interplay between MSCs and either healthy or chronically diseased tendon matrix.
Methods Used in the Research
- The researchers conducted the study using equine MSCs, which were cultured either as standalone cell aggregates or on scaffolds formed from healthy or diseased equine tendons.
Key Findings
- The study revealed that cell aggregate cultures show higher expression of tendon-related matrix genes and higher levels of tissue inhibitors of metalloproteinases (TIMPs).
- The tenogenic transcription factor scleraxis was seen to be upregulated on both healthy and diseased tendon scaffolds.
- Expression of Matrix metalloproteinase (MMPs) was highest in healthy scaffold cultures. In diseased scaffold cultures, expression and activity of MMPs showcased a transient decrease, suggesting early suppression of the MSC matrix remodeling process when in the presence of diseased tendon matrix.
- Scaffold cultures also demonstrated higher release of glycosaminoglycan and collagen when compared to standalone MSC aggregates, especially definitive in those of diseased tendon scaffolds.
Implication of the Findings
- The findings indicate that the use of MSCs in the treatment of chronic tendon disease may not yield the same benefits as seen in acute lesions, given the observed initial reduction in the remodeling process within a diseased tendon environment.
- However, the unaffected tenogenic differentiation following MSC treatment suggests that it still holds potential therapeutic benefits that can help in chronic tendon disease, and further research could explore this in greater detail.
Cite This Article
APA
Doll CU, Niebert S, Burk J.
(2021).
Mesenchymal Stromal Cells Adapt to Chronic Tendon Disease Environment with an Initial Reduction in Matrix Remodeling.
Int J Mol Sci, 22(23), 12798.
https://doi.org/10.3390/ijms222312798 Publication
Researcher Affiliations
- Equine Clinic (Surgery, Orthopedics), Justus-Liebig-University Giessen, Frankfurter Straße 108, 35390 Giessen, Germany.
- Equine Clinic (Surgery, Orthopedics), Justus-Liebig-University Giessen, Frankfurter Straße 108, 35390 Giessen, Germany.
- Equine Clinic (Surgery, Orthopedics), Justus-Liebig-University Giessen, Frankfurter Straße 108, 35390 Giessen, Germany.
MeSH Terms
- Animals
- Bone Morphogenetic Proteins / metabolism
- Cellular Microenvironment
- Chronic Disease
- Extracellular Matrix / metabolism
- Extracellular Matrix / pathology
- Horse Diseases / metabolism
- Horse Diseases / pathology
- Horses
- Mesenchymal Stem Cells / metabolism
- Mesenchymal Stem Cells / pathology
- Tendinopathy / metabolism
- Tendinopathy / pathology
- Tendons / metabolism
- Tendons / pathology
- Tissue Scaffolds / chemistry
Grant Funding
- BU 3110/1-2 / Deutsche Forschungsgemeinschaft
Conflict of Interest Statement
The authors declare no conflict of interest.
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Citations
This article has been cited 5 times.- Schulze-Tanzil GG. Healing of Ligaments and Tendons: Tissue Engineering and Models. Int J Mol Sci 2022 Dec 7;23(24).
- Doll CU, von Pueckler K, Offhaus J, Berner D, Burk J. Characterization of Equine Chronic Tendon Lesions in Low- and High-Field Magnetic Resonance Imaging. Vet Sci 2022 Jun 15;9(6).
- Roth SP, Burk J, Brehm W, Troillet A. MSC in Tendon and Joint Disease: The Context-Sensitive Link Between Targets and Therapeutic Mechanisms. Front Bioeng Biotechnol 2022;10:855095.
- Burk J, Sassmann A, Kasper C, Nimptsch A, Schubert S. Extracellular Matrix Synthesis and Remodeling by Mesenchymal Stromal Cells Is Context-Sensitive. Int J Mol Sci 2022 Feb 3;23(3).
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