Optimisation of a Tissue Engineering Product based on Mesenchymal Stromal Cells aiming to regenerate bony tissue
Bone is a highly organised and specialised connective tissue that provides a rigid, protective and supporting framework to the body. In addition to this, bone is unique in its capacity to self-regenerate without the formation of a fibrotic scar. Despite its natural healing potential, bone is not alw...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2018 |
| País: | España |
| Institución: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/664844 |
| Acceso en línea: | http://hdl.handle.net/10803/664844 |
| Access Level: | acceso abierto |
| Palabra clave: | Enginyeria de teixits Ingeniería de tejidos Tissue engineering Regeneració (Biologia) Regeneración (Biología) Regeneration (Biologia) Teixits ossis Tejido óseo Medicina regenerativa Regenerative medicine Bones Ciències de la Salut 577 |
| Sumario: | Bone is a highly organised and specialised connective tissue that provides a rigid, protective and supporting framework to the body. In addition to this, bone is unique in its capacity to self-regenerate without the formation of a fibrotic scar. Despite its natural healing potential, bone is not always able to repair large defects, which can result in permanent bone loss and fracture non-unions. Consequently, interventions such as bone grafting are required to replace damaged or diseased bone, accounting for more than two million grafted bones in the world annually. Currently, autografts are still qualified as the gold standard technique, but this option is not exempt of complications such as infections and donor site morbidity. Advanced therapies (AT), particularly regenerative medicine (RM) and tissue engineering (TE) approaches, provide valuable tools with broad applicability in the orthopaedic field with the aim of achieving bone regeneration. This PhD project was developed within the RM field aiming to optimise the formulation of tissue engineering products (TEPs) composed of mesenchymal stromal cells (MSCs) for bone regeneration. To date, MSC-based therapies have been demonstrated safe and some initial signs of efficacy have already been found in several clinical indications; that is why current major challenges rely on improving the efficacy of such therapies by modifying formulations paying special attention to the tissue source of MSCs as well as to the non-cellular components of the final TEPs. The proposal reported in this PhD project is based on the use of MSCs derived either from bone marrow (BM) or the Wharton’s jelly (WJ) of the umbilical cord (UC) as the osteogenic component of the TEP, decellularised bony particles providing osteoinductive and osteoconductive cues and a hydrogel made of fibrin which confers the ability of adapting to the architecture of each particular defect. The investigation has been performed in vitro and in vivo in an ectopic mice model (addressed in CHAPTER IV) and subsequently in two orthotopic ovine models (addressed in CHAPTER III and CHAPTER V) demonstrating an excellent safety profile and signs of efficacy. The new BM-derived MSCs-based clinical grade formulation developed in this work resulted feasible, effective and efficiently adapted to the architecture of simulated cylindrical bone defects. On the other hand, this work is a milestone in the non-clinical development of WJ-MSCs-derived TEPs prior to use in patients. Nonetheless, further investigations in order to trigger the osteogenic commitment of WJ-derived MSCs for specific bone regeneration indications are required. In addition, the outcomes relating to the injectable bone formulation make it an attractive alternative to be considered in future TE approaches regarding three dimensional (3D) bioprinting, as a potential MSC-based bioink. |
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