Mixed cell therapy of bone marrow-derived mesenchymal stem cells and articular cartilage chondrocytes ameliorates osteoarthritis development

Abstract

Of the many cell-based treatments that have been tested in an effort to regenerate osteoarthritic articular cartilage, none have ever produced cartilage that compare with native hyaline cartilage. Studies show that different cell types lead to inconsistent results and for cartilage regeneration to be considered successful, there must be an absence of fibrotic tissue. Here we report of a series of experiments in which bone marrow-derived stem cells (BMSCs) and articular cartilage chondrocytes (ACCs) were mixed in a 1:1 ratio and tested for their ability to enhance cartilage regeneration in three different conditions: (1) in an in vitro differentiation model; (2) in an ex vivo cartilage defect model implanted subcutaneously in mice; and (3) as an intra-articular injection in a meniscectomy-induced OA model in rats. The mixed cells were compared with monocultures of BMSCs and ACCs. In all three experimental models there was significantly enhanced cartilage regeneration and decreased fibrosis in the mixed BMSCs+ACCs group compared with the monocultures. Molecular analysis showed a reduction in vascularization and hypertrophy, coupled with higher chondrogenic gene expression resulting from the BMSCs+ACCs treatment. Together, our data suggest that mixed BMSCs+ACCs treatment is highly chondro-protective and is more effective in regenerating damaged cartilage in both the ex vivo cartilage defect and post-trauma OA disease models. The results from this approach could potentially be used for regeneration of cartilage in OA patients.

Ameliorative effects of ginseng and ginsenosides on rheumatic diseases

“…Knee replacement surgery using titanium can relieve pain and disability. However, there are ongoing studies to develop disease-modifying agents for OA to target disease processes, not symptoms [43], [44], [45], [46], such as cell-mediated therapy with intraarticular injection [47], [48], [49], [50].…”

Current Advances in the Regeneration of Degenerated Articular Cartilage: A Literature Review on Tissue Engineering and Its Recent Clinical Translation

“…A similar injectable was also tested by Qu et al (2021), and the aim was to deliver BM-MSCs using open-porous PLGA microspheres via alkaline treatment, and the results of both in vitro studies and in vivo studies using Sprague-Dawley rat osteochondral defect models confirmed improved articular cartilage regeneration [54]. In a previous study by Prasadam et al (2018), authors aimed to deliver a co-culture of MSCs and chondrocytes as an injectable. For evaluating this co-culture system, in vitro studies, ex vivo studies using a cartilage defect model implanted subcutaneously in NOD-SCID mice, as well as in vivo studies using Wistar rat models with knee OA were performed.…”

“…Microfracture ± HA ± haMPCs [55] AD-MSCs ± allogeneic cartilage from fresh cadavers [56] Intra-articular injection of autologous SVF [57] Intra-articular injections of allogeneic haMPCs [58]…”

Combating Osteoarthritis through Stem Cell Therapies by Rejuvenating Cartilage: A Review

“…However, in a study, the coculture of human infrapatellar fat pad-derived stem cells (IPF-ASCs) and chondrons was unable to promote chondrogenic differentiation [ 58 ]. BMSCs and articular chondrocytes were cocultured in 1 : 1 ratio in different models and injected in OA-induced rats; as a consequence, the reduced vascularization and hypertrophy along with increased expression of chondrogenic gene was found [ 59 ]. Further, in an interesting study, the suspension coculture of hMSCs and hACs was used, which yielded 4.74-fold increase in 3-dimensional aggregates of chondrocytes till 16 days [ 60 ].…”

“…This suggests that SMSCs not only retain their MSC characteristics but might also inhibit the advancement of OA through genetic machinery. Further, SMSCs have demonstrated the ability to enhance the repair of longitudinally torn menisci in avascular areas in a miniature pig model [ 59 ]. In 2014, Hatsushika et al further demonstrated that intra-articularly injected MSCs in pig knee joint regenerated cartilage in resected medial meniscus [ 101 ].…”