Faculty Opinions recommendation of Inhibition of TGF-β signaling in mesenchymal stem cells of subchondral bone attenuates 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.

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Attenuation of Trauma-induced Osteoarthritis by Repetitive Intra-articular Administration of Peripheral Blood Derived Mesenchymal Stem Cells

10.21203/rs.3.rs-910616/v1 ◽

2021 ◽

Author(s):

Weiping Lin ◽

Zhengmeng Yang ◽

Liu Shi ◽

Haixing Wang ◽

Qi Pan ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Articular Cartilage ◽

Subchondral Bone ◽

Peripheral Blood ◽

Cartilage Degradation ◽

Cartilage Tissue ◽

Synovial Joint ◽

Post Surgery ◽

Sham Surgery

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.

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Treatment of chondral defects of the knee with one step matrix-assisted technique enhanced by autologous concentrated bone marrow: In vitro characterisation of mesenchymal stem cells from iliac crest and subchondral bone

Injury ◽

10.1016/j.injury.2010.09.027 ◽

2010 ◽

Vol 41 (11) ◽

pp. 1172-1177 ◽

Cited By ~ 73

Author(s):

Laura de Girolamo ◽

Giulia Bertolini ◽

Matteo Cervellin ◽

Gabriella Sozzi ◽

Piero Volpi

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Subchondral Bone ◽

Iliac Crest ◽

Chondral Defects ◽

Concentrated Bone Marrow ◽

One Step

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Mangiferin stimulates chondrogenic differentiation of mesenchymal stem cells from subchondral bone and targets multiple aspects of smads and SOX9 pathways

Osteoarthritis and Cartilage ◽

10.1016/j.joca.2014.02.681 ◽

2014 ◽

Vol 22 ◽

pp. S368

Author(s):

J. Huh ◽

P. Koh ◽

B-K. Seo ◽

Y-H. Baek ◽

D-Y. Choi ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Subchondral Bone ◽

Chondrogenic Differentiation

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Bone marrow mesenchymal stem cells in rheumatoid arthritis, spondyloarthritis, and ankylosing spondylitis: problems rather than solutions?

Arthritis Research & Therapy ◽

10.1186/s13075-019-2014-8 ◽

2019 ◽

Vol 21 (1) ◽

Cited By ~ 5

Author(s):

Jean-Marie Berthelot ◽

Benoit Le Goff ◽

Yves Maugars

Keyword(s):

Rheumatoid Arthritis ◽

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Ankylosing Spondylitis ◽

Animal Models ◽

Subchondral Bone ◽

Frequent Relapses ◽

Marrow Mesenchymal Stem Cells ◽

Bone Cortex

Abstract Background Bone marrow mesenchymal stem cells (BM-MSCs) can dampen inflammation in animal models of inflammatory rheumatisms and human osteoarthritis. They are expected to be a solution for numerous human conditions. However, in rheumatoid arthritis (RA) and spondyloarthritis (SpA), subsets of subchondral BM-MSCs might conversely fuel synovitis and enthesitis. Main text Abnormal behaviour of BM-MSCs and/or their progeny has been found in RA and SpA. BM-MSCs also contribute to the ossifying processes observed in ankylosing spondylitis. Some synovial fibroblastic stem cells probably derive from BM-MSCs, but some stem cells can also migrate through the bare zone area of joints, not covered by cartilage, into the synovium. BM-MSCs can also migrate in the synovium over tendons. Sub-populations of bone marrow stem cells also invade the soft tissue side of enthesis via small holes in the bone cortex. The present review aims (1) to make a focus on these two aspects and (2) to put forward the hypothesis that lasting epigenetic changes of some BM-MSCs, induced by transient infections of the bone marrow close to the synovium and/or entheses (i.e. trained immunity of BM-MSCs and/or their progeny), contribute to the pathogenesis of inflammatory rheumatisms. Such hypothesis would fit with (1) the uneven distribution and/or flares of arthritis and enthesitis observed at the individual level in RA and SpA (reminiscent of what is observed following reactive arthritis and/or in Whipple’s disease); (2) the subchondral bone marrow oedema and erosions occurring in many RA patients, in the bare zone area; and (3) the frequent relapses of RA and SpA despite bone marrow transplantation, whereas most BM-MSCs resist graft preconditioning. Conclusion Some BM-MSCs might be more the problem than the solution in inflammatory rheumatisms. Subchondral bone marrow BM-MSCs and their progeny trafficking through the bare zone area of joints or holes in the bone cortex of entheses should be thoroughly studied in RA and SpA respectively. This may be done first in animal models. Mini-arthroscopy of joints could also be used in humans to specifically sample tissues close to the bare zone and/or enthesis areas.

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Role of Mesenchymal Stem Cells Densities When Injected as Suspension in Joints with Osteochondral Defects

Cartilage ◽

10.1177/1947603517708333 ◽

2017 ◽

Vol 10 (1) ◽

pp. 61-69 ◽

Cited By ~ 7

Author(s):

Elhussein Elbadry Mahmoud ◽

Naosuke Kamei ◽

Goki Kamei ◽

Tomoyuki Nakasa ◽

Ryo Shimizu ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Subchondral Bone ◽

Osteochondral Defect ◽

Deep Layer ◽

Femoral Condyle ◽

Fibrous Tissue ◽

Intraarticular Injection ◽

Control Group ◽

Osteochondral Repair

Objective The aim of this study was to evaluate an intraarticular injection of different doses of autologous mesenchymal stem cells (MSCs) for improving repair of midterm osteochondral defect. Design At 4 weeks postoperative marrow stimulation model bilaterally (3 mm diameter; 4 mm depth) in the medial femoral condyle, autologous MSCs were injected into knee joint. Twenty-four Japanese rabbits aged 6 months were divided randomly into 4 groups ( n = 6 per group): the control group and and MSC groups including 0.125, 1.25, and 6.25 million MSCs. Repaired tissue was assessed macroscopically and histologically at 4 and 12 weeks after intraarticular injection of MSCs. Results At 12 weeks, there was no repair tissue in the control group. The gross appearance of the 1.25 and 6.25 million MSC groups revealed complete repair of the defect with white to pink tissue at 12 weeks. An osteochondral repair was histologically significantly better in the 1.25 and 6.25 million MSC groups than in the control and 0.125 million MSC groups at 4 and 12 weeks, due to presence of hyaline-like tissue in the deep layer at 4 weeks, and at 12 weeks hyaline cartilage formation at the periphery and fibrous tissue containing some chondrocytes in the deep layer of the center of the defect. Subchondral bone was restructured in the 1.25 and 6.25 million MSC groups, although it did not resemble the normal bone. Conclusion An intraarticular injection of 1.25 or 6.25 million MSCs could promote the repair of subchondral bone, even in the case of midterm osteochondral defect.

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Inhibition of TGF-β signaling in mesenchymal stem cells of subchondral bone attenuates osteoarthritis

Nature Medicine ◽

10.1038/nm.3143 ◽

2013 ◽

Vol 19 (6) ◽

pp. 704-712 ◽

Cited By ~ 435

Author(s):

Gehua Zhen ◽

Chunyi Wen ◽

Xiaofeng Jia ◽

Yu Li ◽

Janet L Crane ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Subchondral Bone

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Combination of Intra-Articular and Intraosseous Injections of Platelet Rich Plasma for Severe Knee Osteoarthritis: A Pilot Study

BioMed Research International ◽

10.1155/2016/4868613 ◽

2016 ◽

Vol 2016 ◽

pp. 1-10 ◽

Cited By ~ 22

Author(s):

Mikel Sánchez ◽

Diego Delgado ◽

Pello Sánchez ◽

Emma Muiños-López ◽

Bruno Paiva ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Synovial Fluid ◽

Knee Joint ◽

Knee Osteoarthritis ◽

Subchondral Bone ◽

Platelet Rich Plasma ◽

Joint Function ◽

Novel Approach ◽

New Strategy

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.

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