scholarly journals Joint Distraction Combined with Mesenchymal Stem Cell Intra-articular Injection Attenuates Osteoarthritis

Author(s):  
Yuanfeng Chen ◽  
Chuanwei Sun ◽  
Wenping Liu ◽  
Yuxin Sun ◽  
Sien Lin ◽  
...  

Abstract Background: Conservative treatments of osteoarthritis (OA) are limited to symptom relief and novel methods to attenuate OA progression are lacking.Objective: In this study, we investigated the effectiveness of knee joint distraction (KJD) combined with mesenchymal stem cells (MSCs) intra-articular injection (KJD+MSCs) in OA rat model.Methods: OA rat model was established by anterior cruciate ligament transection plus medial meniscus resection in right knee in SD rat. The KJD+MSCs treatment started 3 weeks after the OA surgery. There were two other groups as knee joint distraction only (KJD) and no treat (OA). Three weeks after the treatment, distraction external fixators were removed and rats were kept for further 3 weeks. The rats were then terminated, samples were subject to micro-CT and histology examinations to evaluate the changes of the articular cartilage tissues, subchondral bone and the secondary inflammation.Results: Safranin-O/fast green staining showed that articular cartilage injury was most obvious in the OA group than that in the KJD group and the least in the KJD+MSCs group. Immunohistochemistry examinations showed that the KJD+MSCs group had the lowest percentage of MMP13 or ColX positive chondrocytes comparing to other groups. Micro-CT data indicated that the abnormal change in the subchondral region of the tibia in the KJD+MSCs group was significantly less than that in the KJD group or OA group. Finally, immunohistochemistry result showed that the knee joint in the KJD+MSCs group had the least number of CD68-positive cells among all the groups.Conclusions: Joint distraction combined with mesenchymal stem cells injection alleviated cartilage degradation, reduced irregular ossification of subchondral bone and secondary inflammation, suggesting it could be a new method to halt the OA progression.

2022 ◽  
Vol 12 ◽  
Author(s):  
Aifeng Liu ◽  
Jixin Chen ◽  
Juntao Zhang ◽  
Chao Zhang ◽  
Qinxin Zhou ◽  
...  

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.


Author(s):  
Nikolai MALYUK ◽  
◽  
Yuliia DEMIANTSEVA ◽  
Yuriy KHARKEVYCH ◽  
Roman BOKOTKO ◽  
...  

The purpose of the study was to investigate the regenerative processes in the knee joint of rabbits with experimental osteoarthritis after using of allogeneic bone marrow stem cells and a traditional treatment with the non-steroidal anti-inflammatory drug Meloxicam. For the experiment were used 27 male California rabbits (males). Three groups of animals were formed: a control group; the first experimental group treated by the traditional method; the second experimental group treated with allogeneic mesenchymal stem cells (MSC). Animals in the three groups were subjected to osteoarthritis of the knee joint by double injection of 3.44% retinol acetate into the joint cavity at a dose of 1 ml at intervals of 7 days. Tissue from the affected site was sampled for histological examination at 7, 14 and 28 days. The histological sections were stained with haematoxylin-eosin and examined under a microscope. It has been established that intra-articular administration of 3.5 × 106 cells of allogeneic MSCs in experimental osteoarthritis contributes to the restoration of the superficial layer of cartilage, as evidenced by the formation of columns of chondrocytes in the middle layer of articular cartilage and the appearance of isogenic groups of cartilage cells with basophilic cytoplasm in the matrix, uniform articular surface. The use of the traditional method of treating rabbits using the drug Meloxicam is accompanied by incomplete chondrogenesis: part of the chondrocytes is localized in typical chambers, in some cases chondrocyte chambers did not differentiate; articular cartilage had unequal thickness, cell placement was uneven.


2021 ◽  
Author(s):  
Weiping Lin ◽  
Zhengmeng Yang ◽  
Liu Shi ◽  
Haixing Wang ◽  
Qi Pan ◽  
...  

Abstract Background: Osteoarthritis (OA) is a chronic joint disease, characterized by articular cartilage degradation, subchondral bone hardening, and inflammation of the whole synovial joint. There is no pharmacological treatment in slowing down OA progression, leading to costly surgical interventions eventually. Cell therapy using chondrocytes or progenitor cells from different sources has been reported in clinical trials for OA management with some success, but outcomes are varied. Peripheral blood derived mesenchymal stem cells (PB-MSCs) are promising cells owing to their easy collection, superior migration, and differentiation potentials. In the current study, we evaluated the effect of intra-articular administration of PB-MSCs on the progression of OA in mice.Methods: C57BL/6J mice (8-10 weeks old male) were subjected to destabilization of the medial meniscus surgeries (DMM) on their right joints following protocols as previously reported. The mice after DMM were randomly treated with saline (vehicle control), PB-MSCs, or adipose tissue derived MSCs (AD-MSCs) (n = 7 per group). The mice treated with sham surgery were regarded as sham controls (n = 7). PB-MSCs and AD-MSCs were harvested and cultured according to previous published protocols, and pre-labeled with BrdU for 48 h before use. PB-MSCs or AD-MSCs (5 × 105 cells/mouse; passage 3~5) were injected into the right knee joints thrice post-surgery (except sham surgery group). The mice were euthanized at 8 weeks post-surgery and knee joint samples were collected for micro-CT and histological examinations.Results: PB-MSCs administration significantly reduced hardening of subchondral bone comparing to vehicle controls. Safranin O staining showed that PB-MSCs treatment ameliorated degeneration of articular cartilage, which is comparable to AD-MSCs treatment. The expression of catabolic marker MMP13 was significantly reduced in articular cartilage of PB-MSCs-treated groups comparing to vehicle controls. Co-expression of BrdU and Sox9 were detected, indicating injected PB-MSCs differentiated towards chondrocytes in situ. Reduced level of IL-6 in the peripheral sera of PB-MSCs- and AD-MSCs-treated mice was also determined. Conclusions: Repetitive administration of PB-MSCs or AD-MSCs halted OA progression through inhibiting cartilage degradation and inflammation. PB-MSCs may become a promising cell source for cartilage tissue repair and alleviation of OA progression.


2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Mikel Sánchez ◽  
Diego Delgado ◽  
Pello Sánchez ◽  
Emma Muiños-López ◽  
Bruno Paiva ◽  
...  

The aim of this study was to assess a novel approach to treating severe knee osteoarthritis by targeting synovial membrane, superficial articular cartilage, synovial fluid, and subchondral bone by combining intra-articular injections and intraosseous infiltrations of platelet rich plasma. We explored a new strategy consisting of intraosseous infiltrations of platelet rich plasma into the subchondral bone in combination with the conventional intra-articular injection in order to tackle several knee joint tissues simultaneously. We assessed the clinical outcomes through osteoarthritis outcome score (KOOS) and the inflammatory response by quantifying mesenchymal stem cells in synovial fluid. There was a significant pain reduction in the KOOS from baseline(61.55±14.11)to week 24(74.60±19.19), after treatment(p=0.008), in the secondary outcomes (symptoms,p=0.004; ADL,p=0.022; sport/rec.,p=0.017; QOL,p=0.012), as well as VAS score (p<0.001) and Lequesne Index(p=0.008). The presence of mesenchymal stem cells in synovial fluid and colony-forming cells one week after treatment decreased substantially from7.98±8.21 MSC/μL to4.04±5.36 MSC/μL(p=0.019)and from601.75±312.30to139.19±123.61  (p=0.012), respectively. Intra-articular injections combined with intraosseous infiltrations of platelet rich plasma reduce pain and mesenchymal stem cells in synovial fluid, besides significantly improving knee joint function in patients with severe knee osteoarthritis. This trial is registered on EudraCT with the number2013-003982-32.


2020 ◽  
Vol 21 (10) ◽  
pp. 3589 ◽  
Author(s):  
Daiki Murata ◽  
Ryota Fujimoto ◽  
Koichi Nakayama

Osteoarthritis (OA) is a major joint disease that promotes locomotor deficiency during the middle- to old-age, with the associated disability potentially decreasing quality of life. Recently, surgical strategies to reconstruct both articular cartilage and subchondral bone for OA have been diligently investigated for restoring joint structure and function. Adipose tissue-derived mesenchymal stem cells (AT-MSCs), which maintain pluripotency and self-proliferation ability, have recently received attention as a useful tool to regenerate osteocartilage for OA. In this review, several studies were described related to AT-MSC spheroids, with scaffold and scaffold-free three-dimensional (3D) constructs produced using “mold” or “Kenzan” methods for osteochondral regeneration. First, several examples of articular cartilage regeneration using AT-MSCs were introduced. Second, studies of osteochondral regeneration (not only cartilage but also subchondral bone) using AT-MSCs were described. Third, examples were presented wherein spheroids were produced using AT-MSCs for cartilage regeneration. Fourth, osteochondral regeneration following autologous implantation of AT-MSC scaffold-free 3D constructs, fabricated using the “mold” or “Kenzan” method, was considered. Finally, prospects of osteochondral regeneration by scaffold-free 3D constructs using AT-MSC spheroids were discussed.


2015 ◽  
Vol 8 (5) ◽  
pp. 467-474 ◽  
Author(s):  
Yasunari Ikuta ◽  
Naosuke Kamei ◽  
Masakazu Ishikawa ◽  
Nobuo Adachi ◽  
Mitsuo Ochi

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