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Cartilage derived from equine induced pluripotent stem cells: an in vitro and ex vivo One Medicine approach for osteoarthritis

Descripción del proyecto

Terapia celular para la artrosis equina

La artrosis es una enfermedad degenerativa relacionada con la desintegración del cartílago que envuelve los huesos de las articulaciones. Esta enfermedad no se limita a las personas, sino que también se encuentra comúnmente en los caballos. La medicina regenerativa a través de la infiltración de células madre en la articulación afectada constituye un método atractivo para la autorregeneración. En el proyecto CAREQiPSC, financiado con fondos europeos, se proponen desarrollar células madre pluripotentes inducidas de caballos como fuente ilimitada de células con fines terapéuticos. Los investigadores caracterizarán dichas células y evaluarán su potencial para diferenciarse en condrocitos «in vitro» y en matrices tridimensionales. La información sobre su apoyo biomecánico y su potencial terapéutico determinará su futura aplicación en el tratamiento de la artrosis equina.

Objetivo

Osteoarthritis is a degenerative joint pathology that constitutes the first cause of disability in older adults and accounts for >80% of chronic lameness in horses. Effective treatments are not available while developing them is of utmost importance for the EU objective of translating knowledge into society’s benefit. Induced pluripotent stem cells (iPSCs) can provide unlimited cells for therapy with no ethical concerns. However, pre-clinical knowledge is limited to small animals with low translational potential. Larger species such as the horse better resembles human joint’s features and can also benefit from these therapies (One Medicine). To develop this approach, the first mandatory step is obtaining suitable cartilage from eqiPSCs. Thus, the goals of CAREQiPSC are: 1) establishing eqiPSCs from new sources with potential chondrogenic commitment, 2) derive mesenchymal-like cells with chondrogenic potential, 3) compare their chondrogenic ability under different conditions, 4) explore their therapeutic potential in an ex vivo cartilage explant system. To achieve these goals, eqiPSCs will be established from articular chondrocytes, umbilical cord mononuclear cells, and dermal fibroblasts, and their pluripotency will be studied. Mesenchymal cells derived from these lines will be characterised and induced to differentiate in the customary pellet system and in a 3D scaffold. The tissue obtained will be studied by histology, protein and gene expression, and its therapeutic potential will be investigated in cartilage explants, also including imaging and biomechanical assessment. The researcher’s previous experience in the equine model and the host’s expertise in iPSCs and infrastructure will ensure the achievement of these goals. The main outcome will be critical in vitro and ex vivo knowledge to facilitate in vivo application in the horse, which will generate preclinical information transferable to human therapy and will advance the veterinary medicine field.

Coordinador

UNIVERSITY OF GALWAY
Aportación neta de la UEn
€ 184 590,72
Dirección
UNIVERSITY ROAD
H91 Galway
Irlanda

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Región
Ireland Northern and Western West
Tipo de actividad
Higher or Secondary Education Establishments
Enlaces
Coste total
€ 184 590,72