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Fetal Immunomodulatory Environment Following Cartilage Injury-The Key to CARTILAGE Regeneration?
Iris Ribitsch1, Andrea Bileck2, Monika Egerbacher3
1VETERM, Equine Surgery Unit, Department of Companion Animals and Horses, University of Veterinary Medicine Vienna, 1210 Vienna, Austria.
International Journal of Molecular Sciences
|December 10, 2021
Summary
Fetal cartilage regeneration differs from adult osteoarthritis. Researchers compared fetal and adult sheep cartilage injury responses, identifying key fetal regenerative factors and potential mesenchymal stem cell (MSC) therapies.
Area of Science:
- Regenerative medicine
- Comparative pathology
- Biomaterials science
Background:
- Articular cartilage in fetal mammals regenerates fully after injury, unlike in adult mammals where injury leads to osteoarthritis (OA).
- Understanding the molecular mechanisms underlying fetal cartilage regeneration is crucial for developing novel OA therapeutics.
Purpose of the Study:
- To compare the in vivo injury response of fetal and adult ovine articular cartilage histologically and proteomically.
- To identify key factors contributing to fetal cartilage regeneration.
- To compare the secretome of fetal ovine mesenchymal stem cells (MSCs) with injured fetal cartilage to identify potential MSC-derived therapeutic factors.
Main Methods:
- Histological analysis of ovine articular cartilage following injury.
- Proteomic analysis of injured fetal and adult ovine cartilage.
- In vitro secretome analysis of fetal ovine MSCs.
- Comparison of in vivo and in vitro proteomic data.
Main Results:
- Cartilage injury induced significant cellular changes in the synovial membrane, with distinct immune cell infiltrates (macrophages in fetuses, neutrophils in adults).
- Proteomics revealed differential regulation of inflammatory mediators and growth factors between fetal and adult joints post-injury.
- Adult cartilage showed upregulation of neutrophil-related and acute phase proteins, while fetal cartilage exhibited higher expression of immunomodulating proteins and growth factors.
- Seventeen proteins were commonly upregulated in both in vitro MSC secretomes and in vivo fetal regenerative cartilage, indicating therapeutic potential.
Conclusions:
- Fetal cartilage regeneration involves distinct immune responses and molecular signaling compared to adult OA.
- Fetal ovine MSCs possess a secretome with potential therapeutic factors for cartilage repair.
- Biomimicking the fetal regenerative signature, particularly its paracrine factors, offers a promising avenue for developing new OA therapeutics by modulating inflammation and reprogramming macrophages.
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