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Theses

Caractérisation et étude des potentialités chondrogéniques des cellules souches mésenchymateuses d’origine synoviale pour le traitement des lésions focales et diffuses du cartilage

Abstract : Joint cartilage is avascular and not innervated, which gives it very limited repair capabilities. Current surgical treatments do not provide repair tissue similar to native cartilage. For many years, research has been focused on cellular and tissue engineering of cartilage depending on the type of lesions to be treated, focal or diffuse. Mesenchymal stem cells (MSCs) are an interesting cellular source for cartilage engineering. They are easily accessible and have the potential for chondrogenic differentiation. MSCs from bone marrow are the most studied and are the gold-standard. Other MSCs sources of are also very promising. We chose MSCs from the synovial membrane and synovial fluid. These both joint tissues have the advantage of being easily retrievable during arthroscopic examination and their MSCs are adapted to the microenvironment (hypoxia, inflammation) of the joint. This thesis work focused on the study of two cellular sources of synovial origin in the treatment of focal and diffuse cartilage lesions. These synovial-derived MSCs were first characterized according to their phenotypes and their ability to differentiate to the osteogenic, adipogenic and chondrogenic pathways, compared to bone marrow derived MSCs. Then, the chondrogenic capacities of these synovial MSCs to produce a cartilage substitute for the treatment of focal lesions of joint cartilage were studied. The MSCs were seeded in a collagenic biomaterial and different environmental conditions (growth factors and oximetry) were evaluated to define the most appropriate culture conditions. Chondrogenesis has been induced with success by the use of growth factors such as TGF-β1 or TGF-β3 alone or in combination with BMP-2. Hypoxia has not exerted a beneficial effect on matrix synthesis in cartilage substitutes.Finally, we evaluated the ability of CSMs from human synovial fluid to treat diffuse cartilage lesions induced by an anterior cruciate ligament section model in athymic rats. The two intra-articular injections of synovial fluid MSCs, 1 and 2 weeks after surgery did not prevent osteoarthritic lesions.
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Theses
File URL :
http://docnum.univ-lorraine.fr/ulprive/DDOC_T_2019_0122_NEYBECKER.pdf
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https://hal.univ-lorraine.fr/tel-02461239
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Submitted on : Thursday, January 30, 2020 - 3:23:05 PM
Last modification on : Tuesday, October 13, 2020 - 10:45:47 AM

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  • HAL Id : tel-02461239, version 1

Citation

Paul Neybecker. Caractérisation et étude des potentialités chondrogéniques des cellules souches mésenchymateuses d’origine synoviale pour le traitement des lésions focales et diffuses du cartilage. Ingénierie biomédicale. Université de Lorraine, 2019. Français. ⟨NNT : 2019LORR0122⟩. ⟨tel-02461239⟩

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