Intra-articular Mesenchymal Stem Cells in Osteoarthritis of the Knee: A Systematic Review of Clinical Outcomes and Evidence of Cartilage Repair

Ha, Chul‐Won; Park, Yong Bum; Kim, Seong Hwan; Lee, Han-Jun

doi:10.1016/j.arthro.2018.07.028

Cited by 128 publications

(149 citation statements)

References 55 publications

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“…One of the main actions of intra-articular treatments, ranging from corticosteroids to hyaluronic acid (HA) and biologic products, is to reduce inflammatory distress within the joint. 6,7 In recent years, there has been a growing interest in the effects of ozone, 8 which can be safely delivered intra-articularly and whose use is in constant increase in an outpatient setting due to the ease of preparation methods. Ozone (O 3 ), a gas discovered in the mid-19th century, is a molecule consisting of 3 atoms of oxygen in a dynamically unstable structure due to the presence of mesomeric states.…”

Section: See Commentary On Page 287mentioning

confidence: 99%

Oxygen–Ozone Therapy for the Treatment of Knee Osteoarthritis: A Systematic Review of Randomized Controlled Trials

Sconza

Respizzi

Virelli

et al. 2020

Arthroscopy: The Journal of Arthroscopic & Related Surgery

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Section: See Commentary On Page 287mentioning

confidence: 99%

Oxygen–Ozone Therapy for the Treatment of Knee Osteoarthritis: A Systematic Review of Randomized Controlled Trials

Sconza

Respizzi

Virelli

et al. 2020

Arthroscopy: The Journal of Arthroscopic & Related Surgery

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“…In recent years, therapies based on stem cells have led to promising approaches for cartilage repair (Medvedeva et al 2018;Patel et al 2019). Laboratory and clinical studies have shown that mesenchymal stem cells (MSCs) can differentiate into chondrocytes and restore cartilage defects (Huang et al 2016;Driessen et al 2017;Ha et al 2019). However, the potential of MSCs is hampered by aberrant cell phenotype, poor self-renewal ability, and reduced ability to differentiate after multiple passages when cultured in vitro.…”

Section: Introductionmentioning

confidence: 99%

Exosomes produced from 3D cultures of umbilical cord mesenchymal stem cells in a hollow-fiber bioreactor show improved osteochondral regeneration activity

2019

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Animal and clinical studies have shown that mesenchymal stem cells (MSCs) play an important role in cartilage repair. The therapeutic effect of mesenchymal stem cells based therapies has been increasingly demonstrated to exosome-mediated paracrine secretion. Here, we investigated the cellular processes and mechanism of exosomes produced by conventional 2D culture (2D-Exos) and exosomes produced from 3D culture (3D-Exos) of umbilical MSCs (U-MSCs) in a hollowfiber bioreactor for the treatment of cartilage repair. We found that the yield of 3D-Exos was 7.5-fold higher than that of 2D-Exos. The in vitro experiments indicated that both 2D-Exos and 3D-Exos can stimulate chondrocyte proliferation, migration, and matrix synthesis, and inhibit apoptosis, with 3D-Exos exerting a stronger effect than 2D-Exos. This effect was partly attributed to the activation of transforming growth factor beta 1 and Smad2/3 signaling. The injection of 2D-Exos and 3D-Exos showed enhanced gross appearance and attenuated cartilage defect; however, 3D-Exos showed a superior therapeutic effect than 2D-Exos. In summary, our study provides novel insights into the chondroprotective effects of exosomes produced from 3D culture of U-MSCs in a hollow-fiber bioreactor. Because of its promising biological function and high yield, 3D-Exos may become a promising therapeutic method for the treatment of cartilage defects.

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“…In non-contact co-culture experiments between MSCs and primary chondrocytes, improvements in chondrocyte proliferation, phenotype maintenance, and enhanced matrix synthesis were shown to be credited to MSC-derived trophic factors [6,7]. A paracrine role of MSCs was further supported by preclinical studies showing that intra-articular injection of MSCs prevented the development of post-traumatic arthritis and promoted cartilage regeneration in damaged joints [8], as well as improved clinical outcomes and indices of cartilage repair in second-look arthroscopy [9].…”

Section: Introductionmentioning

confidence: 94%

Pulsed electromagnetic fields potentiate the paracrine function of mesenchymal stem cells for cartilage regeneration

et al. 2020

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Background: The mesenchymal stem cell (MSC) secretome, via the combined actions of its plethora of biologically active factors, is capable of orchestrating the regenerative responses of numerous tissues by both eliciting and amplifying biological responses within recipient cells. MSCs are "environmentally responsive" to local micro-environmental cues and biophysical perturbations, influencing their differentiation as well as secretion of bioactive factors. We have previously shown that exposures of MSCs to pulsed electromagnetic fields (PEMFs) enhanced MSC chondrogenesis. Here, we investigate the influence of PEMF exposure over the paracrine activity of MSCs and its significance to cartilage regeneration.Methods: Conditioned medium (CM) was generated from MSCs subjected to either 3D or 2D culturing platforms, with or without PEMF exposure. The paracrine effects of CM over chondrocytes and MSC chondrogenesis, migration and proliferation, as well as the inflammatory status and induced apoptosis in chondrocytes and MSCs was assessed.Results: We show that benefits of magnetic field stimulation over MSC-derived chondrogenesis can be partly ascribed to its ability to modulate the MSC secretome. MSCs cultured on either 2D or 3D platforms displayed distinct magnetic sensitivities, whereby MSCs grown in 2D or 3D platforms responded most favorably to PEMF exposure at 2 mT and 3 mT amplitudes, respectively. Ten minutes of PEMF exposure was sufficient to substantially augment the chondrogenic potential of MSC-derived CM generated from either platform. Furthermore, PEMF-induced CM was capable of enhancing the migration of chondrocytes and MSCs as well as mitigating cellular inflammation and apoptosis. Conclusions:The findings reported here demonstrate that PEMF stimulation is capable of modulating the paracrine function of MSCs for the enhancement and re-establishment of cartilage regeneration in states of cellular stress. The PEMF-induced modulation of the MSC-derived paracrine function for directed biological responses in recipient cells or tissues has broad clinical and practical ramifications with high translational value across numerous clinical applications.

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Intra-articular Mesenchymal Stem Cells in Osteoarthritis of the Knee: A Systematic Review of Clinical Outcomes and Evidence of Cartilage Repair

Cited by 128 publications

References 55 publications

Oxygen–Ozone Therapy for the Treatment of Knee Osteoarthritis: A Systematic Review of Randomized Controlled Trials

Oxygen–Ozone Therapy for the Treatment of Knee Osteoarthritis: A Systematic Review of Randomized Controlled Trials

Exosomes produced from 3D cultures of umbilical cord mesenchymal stem cells in a hollow-fiber bioreactor show improved osteochondral regeneration activity

Pulsed electromagnetic fields potentiate the paracrine function of mesenchymal stem cells for cartilage regeneration

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