Evaluation of cartilage biomechanics and knee joint microenvironment after different cell-based treatments in a sheep model of early osteoarthritis

Veronesi, Francesca; Berni, Matteo; Marchiori, Gregorio; Cassiolas, Giorgio; Muttini, Aurelio; Barboni, Barbara; Martini, Lúcia; Fini, Milena; Lopomo, N.; Marcacci, Maurilio; Kon, Elizaveta

doi:10.1007/s00264-020-04701-y

Cited by 20 publications

(22 citation statements)

References 35 publications

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“…Among these, 12 studies (86%) reported positive changes with a decrease in the SF concentration of lymphocytes and inflammatory biomarkers, such as interleukin-1β (IL1-β), IL-6, TNF-α, and prostaglandin E2 (PGE2) [ε]. Moreover, they provided a reduction of SF matrix-degrading enzymes (MMP-3 and MMP-13) and C-terminal telopeptide of type II collagen (CTX2) [ 21 , 22 ], as well as the serum levels of inflammatory markers, such as IL-6, TNFα, S100 Calcium Binding Protein A9 (S100A9), and monocyte chemoattractant protein 1 (MCP-1), the serum levels of cartilage oligomeric matrix protein (COMP), and those of osteoprotegerin (OPG) [ζ].…”

Section: Resultsmentioning

confidence: 99%

Cell-based therapies have disease-modifying effects on osteoarthritis in animal models. A systematic review by the ESSKA Orthobiologic Initiative. Part 1: adipose tissue-derived cell-based injectable therapies

Orfei

Boffa

Sourugeon

et al. 2022

Knee Surg Sports Traumatol Arthrosc

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Purpose The aim of this systematic review was to determine if adipose tissue-derived cell-based injectable therapies can induce disease-modifying effects in joints affected by osteoarthritis (OA). Methods A systematic review was performed on three electronic databases (PubMed, Web of Science, Embase) according to PRISMA guidelines. A synthesis of the results was performed investigating disease-modifying effects in preclinical studies comparing injectable adipose-derived products with OA controls or other products, different formulations or injection intervals, and the combination with other products. The risk of bias was assessed according to the SYRCLE’s tool. Results Seventy-one studies were included (2,086 animals) with an increasing publication trend over time. Expanded cells were used in 65 studies, 3 studies applied point of care products, and 3 studies investigated both approaches. Overall, 48 out of 51 studies (94%) reported better results with adipose-derived products compared to OA controls, with positive findings in 17 out of 20 studies (85%) in macroscopic, in 37 out of 40 studies (93%) in histological, and in 22 out of 23 studies (96%) in immunohistochemical evaluations. Clinical and biomarker evaluations showed positive results in 14 studies out of 18 (78%) and 12 studies out of 14 (86%), while only 9 studies out of 17 (53%) of the imaging evaluations were able to detect differences versus controls. The risk of bias was low in 38% of items, unclear in 51%, and high in (11%). Conclusion The current preclinical models document consistent evidence of disease-modifying effects of adipose-derived cell-based therapies for the treatment of OA. The high heterogeneity of the published studies highlights the need for further targeted research to provide recommendations on the optimal methodologies for a more effective application of these injective therapies for the treatment of OA in clinical practice. Level of evidence II. Graphical Abstract

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Section: Resultsmentioning

confidence: 99%

Cell-based therapies have disease-modifying effects on osteoarthritis in animal models. A systematic review by the ESSKA Orthobiologic Initiative. Part 1: adipose tissue-derived cell-based injectable therapies

Orfei

Boffa

Sourugeon

et al. 2022

Knee Surg Sports Traumatol Arthrosc

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“…To the best of our knowledge, only a pioneering study on bovine cortical bone performed nanomechanical mapping measuring tens of GPa in moduli [ 18 ]. Investigating the small-scale biomechanics of hard tissues is of primary importance to correlate structure and function when the development of regeneration/degeneration phenomena must be detailed in relation to healing, aging and, not least, the presence of biomaterials interfaces [ 19 , 20 , 21 , 22 ]. In these contexts, the richness of detail offered by the AFM topographic mode, when operated in tandem with force mapping, allows for, in principle, the quantitative comparison of local gradients of the mechanical response among different sample regions, as well as those within the same topographic area.…”

Section: Introductionmentioning

confidence: 99%

Nanomechanical Mapping of Hard Tissues by Atomic Force Microscopy: An Application to Cortical Bone

et al. 2022

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Force mapping of biological tissues via atomic force microscopy (AFM) probes the mechanical properties of samples within a given topography, revealing the interplay between tissue organization and nanometer-level composition. Despite considerable attention to soft biological samples, constructing elasticity maps on hard tissues is not routine for standard AFM equipment due to the difficulty of interpreting nanoindentation data in light of the available models of surface deformation. To tackle this issue, we proposed a protocol to construct elasticity maps of surfaces up to several GPa in moduli by AFM nanoindentation using standard experimental conditions (air operation, nanometrically sharp spherical tips, and cantilever stiffness below 30 N/m). We showed how to process both elastic and inelastic sample deformations simultaneously and independently and quantify the degree of elasticity of the sample to decide which regime is more suitable for moduli calculation. Afterwards, we used the frequency distributions of Young’s moduli to quantitatively assess differences between sample regions different for structure and composition, and to evaluate the presence of mechanical inhomogeneities. We tested our method on histological sections of sheep cortical bone, measuring the mechanical response of different osseous districts, and mapped the surface down to the single collagen fibril level.

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“…All mice were euthanized at the designed time points for the harvest of the knee joints. The tibia plateaus were photographed with a Zoom-stereoscopic microscope (Leica, Germany) and evaluated according to the grading system ( Table S1 ) [ 18 ].…”

Section: Methodsmentioning

confidence: 99%

Teriparatide ameliorates articular cartilage degradation and aberrant subchondral bone remodeling in DMM mice

Liu

Chen

et al. 2023

Journal of Orthopaedic Translation

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Evaluation of cartilage biomechanics and knee joint microenvironment after different cell-based treatments in a sheep model of early osteoarthritis

Cited by 20 publications

References 35 publications

Cell-based therapies have disease-modifying effects on osteoarthritis in animal models. A systematic review by the ESSKA Orthobiologic Initiative. Part 1: adipose tissue-derived cell-based injectable therapies

Cell-based therapies have disease-modifying effects on osteoarthritis in animal models. A systematic review by the ESSKA Orthobiologic Initiative. Part 1: adipose tissue-derived cell-based injectable therapies

Nanomechanical Mapping of Hard Tissues by Atomic Force Microscopy: An Application to Cortical Bone

Teriparatide ameliorates articular cartilage degradation and aberrant subchondral bone remodeling in DMM mice

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