Assessment of the Efficacy of Bone Marrow-Derived Mesenchymal Stem Cells against a Monoiodoacetate-Induced Osteoarthritis Model in Wistar Rats

Abstract

Osteoarthritis (OA) of the knee is a debilitating condition that can severely limit an individual’s mobility and quality of life. This study was designed to evaluate the efficacy of bone marrow-derived mesenchymal stem cell (BM-MSC) treatment in cartilage repair using a rat model of monoiodoacetate- (MIA-) induced knee OA. OA was induced in the knee joint of rats by an intracapsular injection of MIA (2 mg/50 μL) on day zero. The rats were divided into three groups ( n = 6 ): a normal control group, an osteoarthritic control group, and an osteoarthritic group receiving a single intra-articular injection of BM-MSCs ( 5 × 10 6 cells/rat). The knee diameter was recorded once per week. By the end of the performed experiment, X-ray imaging and enzyme-linked immunosorbent assay analysis of serum inflammatory cytokines interleukin-1beta (IL-β), IL-6, and tumor necrosis factor-α (TNF-α) and anti-inflammatory cytokines interleukin-10 and transforming growth factor-beta (TGF-β) were carried out. In addition, RT-PCR was used to measure nuclear factor-kappa B (NF-κB), inducible nitric oxide synthase (iNOS), and type II collagen mRNA levels and Western blot analysis was used to determine caspase-3 protein levels in all treated groups. Finally, hematoxylin/and eosin stains were used for histopathological investigation. Administration of BM-MSCs significantly downregulated knee joint swelling and MIA-induced (IL-1β, IL-6, and TNF-α) and upregulated IL-10 and TGF-β as well. Moreover, BM-MSC-treated osteoarthritic rats exhibited decreased expression of NF-κB, iNOS, and apoptotic mediator (caspase-3) and increased expression of type II collagen when compared to rats treated with MIA alone. The hematoxylin/eosin-stained sections revealed that BM-MSC administration ameliorated the knee joint alterations in MIA-injected rats. BM-MSCs could be an effective treatment for inflamed knee joints in the MIA-treated rat model of osteoarthritis, and the effect may be mediated via its anti-inflammatory and antioxidant potential.

Ameliorative Effects of Bone Marrow-derived Mesenchymal Stem Cells and Hyaluronic Acid on Monosodium Iodoacetate-Induced Ankle Osteoarthritis in Wistar Rats: Roles of Th1/Th2/Th17 cytokines, MMP-13, TGF-β1 and antioxidant defense system

“…The osteoarthritic group had a substantial drop in serum GSH content in the current investigation. This is consistent with other previous publications [70,71].…”

Two Amnion-Derived Mesenchymal Stem-Cells Injections to Osteoarthritic Elbows in Dogs—Pilot Study

“…Additionally, MSCs are also able to avoid T-cell proliferation and ensure macrophage polarization [ 244 , 245 , 246 ]. Similarly to our study, other researchers described the up-regulation of IL-10 and down-regulation of IL-1β, IL-6, and TNF-α in OA joint by MSCs exposition [ 247 , 248 ]. Nevertheless, the efficacy of cell-based treatment is affected by many factors including joint state and etiology of the degenerative process.…”

Advances in Stem Cell-Based Therapies in the Treatment of Osteoarthritis

“…C57BL, DBA1, and FVBN mice express the SCA-1 surface marker [ 39 ], while BALB/C mice express SCA-1 [ 40 ]. MSCs are readily accessible and can be isolated from the stroma of almost all organs, with a relatively straight forward isolation process [ 41 ]. MSCs have demonstrated notable efficacy in the treatment of autoimmune diseases and tissue/organ repair.…”

“…Hamdalla HM et al found that BM-MSCs significantly alleviated inflammation in a monosodium iodoacetate (MIA)-induced KOA rat model, improving knee joint swelling. A single intra-articular injection of BM-MSCs markedly downregulated IL-1β, IL-6, and TNF-α while upregulating IL-10 and TGF-β [ 41 ]. Chahal J et al observed a reduction in the levels of the proinflammatory factors IL-12 and p40, decreased proinflammatory monocyte and macrophage subpopulations, and decreased synovial inflammation in late-stage KOA patients after BM-MSC injection, leading to improved passive joint mobility [ 60 ].…”