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Multipotential stromal cells in the talus and distal tibia in ankle osteoarthritis – Presence,potency and relationships to subchondral bone changes
Authors:William G Jones  Jehan J El-Jawhari  C L Brockett  Lekha Koria  Ioannis Ktistakis  Elena Jones
Institution:1. Faculty of Medicine and Health, Leeds Institute of Rheumatoid and Musculoskeletal Medicine, University of Leeds, Leeds, UK;2. Faculty of Medicine and Health, Leeds Institute of Rheumatoid and Musculoskeletal Medicine, University of Leeds, Leeds, UK

Department of Biosciences, School of Science and Technology, Nottingham Trent University, Nottingham, UK

Clinical Pathology Department, Mansoura University, Mansoura, Egypt

Contribution: Conceptualization (equal), Data curation (equal), Resources (supporting), Supervision (equal), Writing - review & editing (lead);3. School of Mechanical Engineering, Institute of Medical and Biological Engineering, University of Leeds, Leeds, UK

Contribution: Conceptualization (equal), Data curation (supporting), Funding acquisition (supporting), Project administration (supporting), Resources (supporting), Supervision (supporting);4. School of Mechanical Engineering, Institute of Medical and Biological Engineering, University of Leeds, Leeds, UK

Contribution: Methodology (supporting), Software (supporting), Validation (supporting), Writing - review & editing (supporting);5. Hull and East Yorkshire Teaching Hospital, Hull, UK

Contribution: Resources (equal), Writing - review & editing (supporting)

Abstract:A large proportion of ankle osteoarthritis (OA) has an early onset and is post-traumatic. Surgical interventions have low patient satisfaction and relatively poor clinical outcome, whereas joint-preserving treatments, which rely on endogenous multipotential stromal cells (MSCs), result in suboptimal repair. This study investigates MSC presence and potency in OA-affected talocrural osteochondral tissue. Bone volume fraction (BV/TV) changes for the loading region trabecular volume and subchondral bone plate (SBP) thickness in OA compared with healthy tissue were investigated using microcomputed tomography. CD271-positive MSC topography was related to bone and cartilage damage in OA tissue, and in vitro MSC potency was compared with control healthy iliac crest (IC) MSCs. A 1.3- to 2.5-fold SBP thickening was found in both OA talus and tibia, whereas BV/TV changes were depth-dependent. MSCs were abundant in OA talus and tibia, with similar colony characteristics. Tibial and talar MSCs were tripotential, but talar MSCs had 10-fold lower adipogenesis and twofold higher chondrogenesis than IC MSCs (P = .01 for both). Cartilage damage in both OA tibia and talus correlated with SBP thickening and CD271+ MSCs was 1.4- to twofold more concentrated near the SBP. This work shows multipotential MSCs are present in OA talocrural subchondral bone, with their topography suggesting ongoing involvement in SBP thickening. Potentially, biomechanical stimulation could augment the chondrogenic differentiation of MSCs for joint-preserving treatments.
Keywords:ankle  multipotential stromal cells  osteoarthritis  regenerative medicine
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