AbstractMusculoskeletal disorders are the main cause for severe long-term pain and physical disability. Degeneration of the joint leads to injury to tissues from the joint, including articular cartilage and tendons. Cartilage injuries are very common, and form a risk factor for the development of osteoarthritis (OA), which is a degenerative and inflammatory condition of synovial joints with irreversible loss of supportive cartilage matrix. Moreover, tendon lesions represent 30% of all musculoskeletal consultations. Unfortunately, both OA and tendinopathy involve tissues that are characterized by a low intrinsic healing capacity and current treatment options are not able to provide full and stable recovery of the damaged tissue. Therefore, there is a growing need for the development of new treatment options for OA, cartilage defects and tendon injuries. Autologous chondrocyte implantation or the transplantation of tendon-derived stem cells have been proposed as efficient cell-based therapies for treating chondral lesions or OA and tendon injuries respectively. However, the usage of adult autologous tissue-specific cells requires a two-step surgery and is associated with several other drawbacks.
For stem cell-based strategies for OA or tendinopathies, mesenchymal stem cells (MSCs) are of particular interest. Most studies using a MSC-based cell therapy focus on bone marrow-derived MSCs (BM-MSCs). However, this type of MSC is associated with several downsides, such as an invasive isolation procedure and hypertrophic differentiation. A promising alternative stem cell niche can be found in tooth-associated tissues, such as the dental pulp or the periodontal ligament tissue. In contrast to BM-MSCs, DPSCs showed a higher proliferative rate and have an easy isolation procedure by which they can be obtained. Additionally, the immunomodulatory properties of DPSCs emphasize their promise as cell-based therapies for immune-related diseases. Periodontal ligament stem cells (PDLSCs) are isolated from the periodontal ligament tissue and have been described to be a promising cell source for tendon-regenerative applications because of their inherent ligamentous nature and their native expression pattern of tendon-associated markers.
In addition to MSCs, platelet concentrates are emerging as promising treatment possibilities because of their high amount in growth factors and cytokines, which have been described to play crucial roles in wound healing and immunomodulation. However, since the well-studied platelet derivative; platelet rich plasma, requires the supplementation of anti-coagulants and biochemical handling before preparation, the use of leukocyte- and platelet-rich fibrin (L-PRF), a second generation platelet concentrate, is encouraged.
The current dissertation evaluated the chondrogenic potential of two completely different biological approaches to treat cartilage lesions or have paracrine-mediated effects in OA. While L-PRF was not able to enhance chondrogenesis or to counteract the cytokine-induced inflammatory state of chondrocytes in vitro, DPSCs showed different beneficial effects including the formation of cartilage-like GAG-rich spheres and anti-inflammatory or anti-catabolic effects in vitro in OA-mimicked chondrocytes. Secondly, DPSCs and PDLSCs were compared to BM-MSCs as a promising therapeutic option for tendon engineering. We indicated that PDLSCs might be a more appropriate cell source over DPSCs and BM-MSCs for tendon regeneration. Finally, as the sheep is emerging as a suitable large animal model for preclinical cartilage research, and ovine DPSCs can be easily isolated, testing their therapeutic efficiency in preclinical studies should be encouraged.
|Date of Award||28 Oct 2020|
|Sponsors||FONDS SPECIAL DE RECHERCHE (FSR)|
|Supervisor||Jean-Michel Vandeweerd (Supervisor), Ivo Lambrichts (Supervisor), Peter D. Clegg (Co-Supervisor), Pascal Gervois (Co-Supervisor), Charles Nicaise (President), Marcel Ameloot (President), Annelies Bronckaers (Jury), Esther Wolfs (Jury), Jean-Francois NISOLLE (Jury), Debby Gawlitta (Jury) & Marc Quirynen (Jury)|