Evaluation of the Effects of Synovial Multipotent Cells on Deep Digital Flexor Tendon Repair in a Large Animal Model of Intra‐Synovial Tendinopathy

Abstract

Intra‐synovial tendon injuries are a common orthopedic problem with limited treatment options. The synovium is a specialized connective tissue forming the inner encapsulating lining of diarthrodial joints and intra‐synovial tendons. It contains multipotent mesenchymal stromal cells that render it a viable source of progenitors for tendon repair. This study evaluated the effects of autologous implantation of cells derived from normal synovium (synovial membrane cells [SMCs]) in augmenting repair in an ovine model of intra‐synovial tendon injury. For this purpose, synovial biopsies were taken from the right digital flexor tendon sheath following creation of a defect to the lateral deep digital flexor tendon. Mononuclear cells were isolated by partial enzymatic digestion and assessed for MSC characteristics. Cell tracking and tendon repair were assessed by implanting 5 × 106 cells into the digital flexor tendon sheath under ultrasound guidance with the effects evaluated using magnetic resonance imaging and histopathology. Synovial biopsies yielded an average 4.0 × 105 ± 2.7 × 105 SMCs that exhibited a fibroblastic morphology, variable osteogenic, and adipogenic responses but were ubiquitously strongly chondrogenic. SMCs displayed high expression of CD29 with CD271NEGATIVE and MHC‐IILOW cell‐surface marker profiles, and variable expression of CD73, CD90, CD105, CD166, and MHC‐I. Implanted SMCs demonstrated engraftment within the synovium, though a lack of repair of the tendon lesion over 24 weeks was observed. We conclude healthy synovium is a viable source of multipotent cells, but that the heterogeneity of synovium underlies the variability between different SMC populations, which while capable of engraftment and persistence within the synovium exhibit limited capacity of influencing tendon repair. © 2019 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society J Orthop Res 38:128–138, 2020

Impact of Electrospun Piezoelectric Core–Shell PVDFhfp/PDMS Mesh on Tenogenic and Inflammatory Gene Expression in Human Adipose-Derived Stem Cells: Comparison of Static Cultivation with Uniaxial Cyclic Tensile Stretching

“…The transcription factor MKX is a central factor regulating tendon-related gene expression; an overexpression of MKX was reported to elevate tendon-related markers in MSCs [ 55 ] and MKX knockout models were shown to exhibit heterotopic ossification of the Achilles tendon in Mkx(−/−) mice and rats [ 56 ]. Given these facts, a prominent induction of in ASCs that are in contact with random PVDFhfp/PDMS holds great promise to act beneficially with regard to induce tenogenic commitment, e.g., for mesenchymal stem cells present in the synovial fluid [ 35 , 57 ].…”

“…The advantage of developing fibers with a PDMS core and a PVDFhfp shell resides in the possibility to obtain highly elastic fibers whose interface with the external environment is controlled by a very stable and biocompatible material. Indeed, the hydrophobic nature of PVDFhfp hinders proper cell attachment, which enlarges the value of a good physical barrier function to prevent tendon adhesion and optimize the gliding capacity in the tendon sheath of intrasynovial tendons [ 32 , 33 , 34 , 35 ].…”

Regenerative medicine in equine orthopaedics: what and when?

“…Mesenchymal stem cells coat the surface of tendon explants in vitro and modulate the release of matrix proteins (Garvican et al, 2014b), hence intra-thecal delivery of MSCs might offer a therapeutic benefit for an injury that is currently managed by debridement but carries a low success rate. However both an experimental study in sheep using both bone marrow-derived and synovium-derived MSCs (Khan et al, 2018;Khan et al, 2020), and a clinical trial in horses, failed to show any benefit in healing of tendon defects inside the digital sheath. Labelling of the cells showed that implanted MSCs engraft ed into the sheath synovium without any cells being present in the tendon defect (Khan et al, 2018;Khan et al, 2020), hence the intra-thecal injection of MSCs is currently not recommended for the treatment of intra-thecal tendon disease.…”

Species variations in tenocytes’ response to inflammation require careful selection of animal models for tendon research

“…39,51,52 Sheep are included because features of clinical tendinopathy of horses could be emulated also in ovine induced models. 51,[53][54][55][56][57] In particular, the ovine intra-synovial tendon lesion model mimics the clinical intra-synovial tendon disease of humans and horses more accurately than small animal extra-synovial models, e.g., with respect to histology and gene expression, to similarities in the biomechanical environment and to failure of lesions to heal. 51,[53][54][55][56][57]…”