The effectiveness of allogeneic mesenchymal stem cells therapy for knee osteoarthritis in pigs

Abstract

Background: Intraarticular injection of the mesenchymal stem cells (MSCs) has shown to be successful for treating osteoarthritis (OA). Nevertheless, many studies have been focusing on autologous MSCs. The following study investigates the safety and effectiveness of intraarticular injection of allogenic MSCs in a pig OA model. Methods: Superparamagnetic iron oxide (SPIO) nanoparticles were labelled with bone marrow-derived mesenchymal stem cells (BM-MSCs) to allow cells tracking using magnetic resonance imaging (MRI). A pig OA model was established by bilateral medial meniscectomy. Next, SPIO-BM-MSCs were injected into the right knee, while the left knee was left untreated. MRI and radiography were used to assess the degree of OA and to evaluate the effectiveness of allogenic MSCs. Hematoxylin and eosin (H&E), safranin-o fast green staining, toluidine blue, and immunohistochemical staining were used to evaluate the therapeutic effect of the injections. Results: At concentration of ≤20 μg/mL, SPIO caused no toxicity to BM-MSCs. Four weeks after surgery, OA changes were observed on MRI scan. The SPIO labeled BM-MSCs were found moving towards the impaired part of the cartilage 8 to 24 h after injections. In addition, no significant differences between the right side (therapeutic side) and the left side (untreated side) were observed following histological and immunohistochemistry analysis. Conclusions: The suitable concentration of SPIO for labelling BMSCs was 20 μg/mL, while the allogenic MSCs could move towards and accumulate around the impaired cartilage. No significant difference was found between treatment and control group.

Conditioned medium of mesenchymal stem cells delays osteoarthritis progression in a rat model by protecting subchondral bone, maintaining matrix homeostasis, and enhancing autophagy

“…In the recent years, mesenchymal stem/stromal cell-based therapy (MSCT) has become a promising way in treating OA. Several studies proved the effect of MSCT in cartilage repair in animal models and even clinical studies (de Windt et al, 2017;Hsu et al, 2018;Koh, Kwon, Kim, Choi, & Tak, 2016;Xia et al, 2018). However, concerning the risk of tumourigenicity (Deng, Zhang, Xie, Zhang, & Tang, 2018), genomic stability, and immunogenicity when using viable cells , there is still a long way before popularization of MSCT in clinical practice.…”

Mesenchymal stromal cells for articular cartilage repair: preclinical studies

“…Likewise, no consistency has been observed for the provided benefit in the two OA studies reported in pigs (Table 2). In a well-defined OA model, Xia et al (2018b) found no difference in BM-MSC-treated lesions relative to controls. However, it is unclear whether the labelling of the MSCs with magnetic nanoparticles affect their protective functions (Xia et al, 2018b).…”

“…In a well-defined OA model, Xia et al (2018b) found no difference in BM-MSC-treated lesions relative to controls. However, it is unclear whether the labelling of the MSCs with magnetic nanoparticles affect their protective functions (Xia et al, 2018b). In contrast, Wu et al (2019) observed improved cartilage repair at both macroscopic and histological levels after two pigs were subjected to a complex surgical intervention of cartilage injury followed by transplantation with UC-MSCs in hyaluronic acid.…”

Stem Cell Treatment for Knee Articular Cartilage Defects and Osteoarthritis

“…Knee degeneration can also be induced in animals through surgical means, such as iatrogenic anterior cruciate ligament transection [25], meniscectomy [26], osteochondral fragmentation [27], or tibial plateau fracture [28]. Studies have included and ranged from small animal models such as rats and rabbits to large animal models such as sheep, pigs, and dogs [26,[29][30][31][32].…”