Osteoarthritis Prevention Through Meniscal Regeneration Induced by Intra-Articular Injection of Meniscus Stem Cells

Abstract

Meniscus injury is frequently encountered in clinical practice. Current surgical therapy involving partial or complete meniscectomy relieves pain in the short-term but often leads to osteoarthritis (OA) in the long-term. Here, this study aimed to identify and characterize a novel population of meniscus-derived stem cells (MeSCs) and develop a new strategy of articular cartilage protection by intra-articular injection of these cells. The ''stemness'' and immune properties of MeSCs were investigated in vitro, while the efficacy of intra-articular injection of MeSCs for meniscus regeneration and OA prevention were investigated in vivo at 4, 8, and 12 weeks postsurgery. MeSCs displayed typical stem cell characteristics such as low immunogenicity and even possessed immunosuppressive function. In a rabbit meniscus injury model, transplantation of allogenous MeSCs did not elicit immunological rejection, but promoted neo-tissue formation with better-defined shape and more matured extracellular matrix. In a rabbit experimental OA model, transplantation of MeSCs further protected joint surface cartilage and maintained joint space at 12 weeks postsurgery, whereas extensive joint surface irregularities and joint space stenosis were observed in the control group. This study thus evoked a new strategy for articular cartilage protection and meniscus regeneration by intra-articular injection of MeSCs for patients undergoing meniscectomy.

Isolation, Characterization, and Multipotent Differentiation of Mesenchymal Stem Cells Derived from Meniscal Debris

“…Whatever the origin of the MSCs in our meniscal debris samples, their properties are similar to those previously reported for human meniscus stem/progenitor cells, which displayed characteristics of MSCs and expressed high levels of Col-II [38, 39]. Those cells promoted meniscus regeneration and ameliorated osteoarthritis through SDF-1/CXCR4-mediated homing in a rat model of meniscus injury.…”

A study to identify and characterize the stem/progenitor cell in rabbit meniscus

“…However, they only tested the expression of CD34, CD45, CD44, CD90, CD105, and CD166 in human meniscus stem cells by flow cytometer without testing other stem cell markers, such as SSEA4, Nanog, Strol-1, nucleostemin, and CD73 (Shen et al 2013(Shen et al , 2014. To our knowledge, there is no such a report on investigation of the characterizations of meniscusderived stem cells with both flow cytometer and immunostaining.…”

Safety Studies for Use of Adipose Tissue-Derived Mesenchymal Stromal/Stem Cells in a Rabbit Model for Osteoarthritis to Support a Phase I Clinical Trial

“…Radiological examination of these same joints did not reveal major areas of joint space narrowing, sclerosis, or osteophyte formation, and we did not find indications for structural cartilage degeneration by H&E staining or safranin O‐fast green staining. Hence, the meniscectomy procedure carried out in our study generated mild preclinical OA symptoms that were far less pronounced than the radiological and/or histological signs of OA that have been previously reported at 8–24 weeks after surgery in models of ACLT [, , ] and meniscal injury [, , ].…”

“…Current treatments for OA are not able to restore normal articular cartilage integrity []. Because of their differentiation capacity, as well as anti‐inflammatory and regenerative trophic functions, stem cells represent a novel treatment option for OA that warrants further investigation in human clinical trials []. Our focus on AMSCs as a resource is primarily driven by their ease of isolation in large quantities as a clinical‐grade product that is expanded in human platelet lysate and used in autologous cell transplantation [].…”