Intra-Articular Injection of Umbilical Cord Mesenchymal Stem Cells Loaded With Graphene Oxide Granular Lubrication Ameliorates Inflammatory Responses and Osteoporosis of the Subchondral Bone in Rabbits of Modified Papain-Induced Osteoarthritis

AimThis study is to investigate the effects of umbilical cord mesenchymal stem cells (UCMSCs) loaded with the graphene oxide (GO) granular lubrication on ameliorating inflammatory responses and osteoporosis of the subchondral bone in knee osteoarthritis (KOA) animal models.MethodsThe KOA animal models were established using modified papain joint injection. 24 male New Zealand rabbits were classified into the blank control group, GO group, UCMSCs group, and GO + UCMSCs group, respectively. The concentration in serum and articular fluid nitric oxide (NO), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), type II collagen (COL-II), and glycosaminoglycan (GAG) was detected using ELISA, followed by the dissection of femoral condyles and staining of HE and Micro-CT for observation via the microscope.ResultsGO granular lubrication and UCMSCs repaired the KOA animal models. NO, IL-6, TNF-α, GAG, and COL-II showed optimal improvement performance in the GO + UCMSCs group, with statistical significance in contrast to the blank group (P <0.01). Whereas, there was a great difference in levels of inflammatory factors in serum and joint fluid. Micro-CT scan results revealed the greatest efficacy of the GO + UCMSCs group in improving joint surface damage and subchondral bone osteoporosis. HE staining pathology for femoral condyles revealed that the cartilage repair effect in GO + UCMSCs, UCMSCs, GO, and blank groups were graded down.ConclusionUCMSCs loaded with graphene oxide granular lubrication can promote the secretion of chondrocytes, reduce the level of joint inflammation, ameliorate osteoporosis of the subchondral bone, and facilitate cartilage repair.

Application Effect of Different Concentrations of Platelet-Rich Plasma Combined with Quadriceps Training on Cartilage Repair of Knee Osteoarthritis

We investigated the application effect of different concentrations of platelet-rich plasma (PRP) combined with quadriceps training on cartilage repair of knee osteoarthritis. Data of 37 patients with knee osteoarthritis (KOA) treated in our hospital (November 2019–February 2021) were retrospectively analyzed and the patients were divided into low concentration group (LCG) (n = 12), medium concentration group (MCG) (n = 12), and high concentration group (HCG) (n = 13) according to the order of admission. All patients received quadriceps training. Three groups above received knee injection of PRP, and the platelet concentrations were 1000–1400 × 109/L, 1400–1800 × 109/L, and 1800–2100 × 109/L, respectively. Articular cartilage thickness of the medial and lateral femur, knee joint function scores, inflammatory factor levels, and matrix metalloproteinases (MMPs) levels were compared. After treatment, compared with the MCG and HCG, articular cartilage thickness of the medial and lateral femur of the diseased side in the LCG was obviously lower ( P < 0.05 ). At 2 months after treatment (T3), compared with the HCG, articular cartilage thickness of the medial and lateral femur of the diseased side in the MCG was obviously higher ( P < 0.05 ), without remarkable difference in articular cartilage thickness of the medial and lateral femur of the healthy side among three groups ( P > 0.05 ). After treatment, compared with the LCG, knee joint function scores of the MCG and HCG were obviously better ( P < 0.001 ). Compared with the HCG, the knee function score at T3 in the MCG was obviously better ( P < 0.001 ). After treatment, compared with the LCG, inflammatory factor levels and levels of MMPs in the MCG and HCG were obviously lower ( P < 0.05 ). Compared with the HCG, inflammatory factor levels and levels of MMPs at T3 in the MCG were obviously lower ( P < 0.05 ). PRP combined with quadriceps training can accelerate cartilage repair of patients with KOA and reduce inflammatory factor levels and levels of MMPs, but the treatment effect of PRP depends on platelet concentration, with the best range of 1400–1800 × 109/L. Too high or too low platelet concentrations will affect recovery of knee function.

The clinical potential of articular cartilage-derived progenitor cells: a systematic review

Over the past two decades, evidence has emerged for the existence of a distinct population of endogenous progenitor cells in adult articular cartilage, predominantly referred to as articular cartilage-derived progenitor cells (ACPCs). This progenitor population can be isolated from articular cartilage of a broad range of species, including human, equine, and bovine cartilage. In vitro, ACPCs possess mesenchymal stromal cell (MSC)-like characteristics, such as colony forming potential, extensive proliferation, and multilineage potential. Contrary to bone marrow-derived MSCs, ACPCs exhibit no signs of hypertrophic differentiation and therefore hold potential for cartilage repair. As no unique cell marker or marker set has been established to specifically identify ACPCs, isolation and characterization protocols vary greatly. This systematic review summarizes the state-of-the-art research on this promising cell type for use in cartilage repair therapies. It provides an overview of the available literature on endogenous progenitor cells in adult articular cartilage and specifically compares identification of these cell populations in healthy and osteoarthritic (OA) cartilage, isolation procedures, in vitro characterization, and advantages over other cell types used for cartilage repair. The methods for the systematic review were prospectively registered in PROSPERO (CRD42020184775).

Osteochondral Lesions of the Tibial Plafond and Ankle Instability With Ankle Cartilage Lesions: Proceedings of the International Consensus Meeting on Cartilage Repair of the Ankle

Background: An international consensus group of experts was convened to collaboratively advance toward consensus opinions based on the best available evidence on key topics within cartilage repair of the ankle. The purpose of this article is to present the consensus statements on osteochondral lesions of the tibial plafond (OLTP) and on ankle instability with ankle cartilage lesions developed at the 2019 International Consensus Meeting on Cartilage Repair of the Ankle. Methods: Forty-three experts in cartilage repair of the ankle were convened and participated in a process based on the Delphi method of achieving consensus. Questions and statements were drafted within 4 working groups focusing on specific topics within cartilage repair of the ankle, after which a comprehensive literature review was performed and the available evidence for each statement was graded. Discussion and debate occurred in cases where statements were not agreed on in unanimous fashion within the working groups. A final vote was then held. Results: A total of 11 statements on OLTP reached consensus. Four achieved unanimous support and 7 reached strong consensus (greater than 75% agreement). A total of 8 statements on ankle instability with ankle cartilage lesions reached consensus during the 2019 International Consensus Meeting on Cartilage Repair of the Ankle. One achieved unanimous support, and seven reached strong consensus (greater than 75% agreement). Conclusions: These consensus statements may assist clinicians in the management of these difficult clinical pathologies. Level of Evidence: Level V, mechanism-based reasoning.

Amniotic Fluid-derived MSC Secretome Halts Action of IL-1β and TNF-α Through ERK/MAPK and Returns Cartilage Repair Under OA Inflammatory Stimuli

Background: Osteoarthritis (OA) is a degenerative cartilage disease. OA cartilage has a limited repair capacity due to the effect of IL-1β and TNF-α on the chondrocyte progenitor cells (CPC) in an OA joint. Mesenchymal stem cells (MSC) therapy is a therapeutic option for osteoarthritis that initiated by the ability of secretory growth factors and mediator molecules to heal OA. Amniotic fluid MSC (AF-MSC), an interesting MSC source, has been shown to secrete various growth factors and anti-inflammatory molecules promoting tissue repair and regeneration. However, the effect of AF-MSC secretory factors to inflammation and cartilage repair is still limited. The current study aims to explore the action of AF-MSC secretome to IL-1β and TNF-α, and the CPC function that encourages cartilage repair.Methods: The effect of AF-MSC secretome to OA inflammatory cytokines was observed via the CPC migration using scratch assay. Inhibitory action of AF-MSC secretome to IL-1β and TNF-α was determined through NF-κB and MAPK signaling pathways by western blot. The repaired function of OA cartilage was analyzed via the cartilage outgrowth study and the expression of chondrogenic and anabolic genes using qRT-PCR.Results: AF-MSC secretome can arrest inflammatory action of IL-1β and TNF-α and reduces production of NF-κB, pNF-κB, p38, pp38, ERK, COX-2, and iNOS signaling proteins. It significantly reduced the production of pERK (P = 0.0434). For cartilage repair, AF-MSC secretome promotes CPC outgrowth and migration in human OA cartilage, even under inflammatory stimuli. By the action of AF-MSC secretome, the inflamed CPC can restore Col II and anabolic genes; IGF1 expression, indicating reactivation of cartilage regeneration.Conclusion: AF-MSC secretory factors have the ability to halt inflammatory actions of IL-1β and TNF-α via the ERK/MAPK pathway and motivate CPC function and anabolic property.