Human adipose-derived Mesenchymal stem cells, low-intensity pulsed ultrasound, or their combination for the treatment of knee osteoarthritis: study protocol for a first-in-man randomized controlled trial

Abstract

Background Human adipose-derived Mesenchymal stem cells (HADMSCs) have proven their efficacy in treating osteoarthritis (OA), in earlier preclinical and clinical studies. As the tissue repairers are under the control of mechanical and biochemical signals, improving regeneration outcomes using such signals has of late been the focus of attention. Among mechanical stimuli, low-intensity pulsed ultrasound (LIPUS) has recently shown promise both in vitro and in vivo. This study will investigate the potential of LIPUS in enhancing the regeneration process of an osteoarthritic knee joint. Methods This study involves a prospective, randomized, placebo-controlled, and single-blind trial based on the SPIRIT guidelines, and aims to recruit 96 patients initially diagnosed with knee osteoarthritis, following American College of Rheumatology criteria. Patients will be randomized in a 1:1:1 ratio to receive Intraarticular HADMSCs injection with LIPUS, Intraarticular HADMSCs injection with shame LIPUS, or Normal saline with LIPUS. The primary outcome is Western Ontario and McMaster Universities Index of OA (WOMAC) score, while the secondary outcomes will be other knee structural changes, and lower limb muscle strength such as the knee cartilage thickness measured by MRI. Blinded assessments will be performed at baseline (1 month prior to treatment), 1 month, 3 months, and 6 months following the interventions. Discussion This trial will be the first clinical study to comprehensively investigate the safety and efficacy of LIPUS on stem cell therapy in OA patients. The results may provide evidence of the effectiveness of LIPUS in improving stem cell therapy and deliver valuable information for the design of subsequent trials. Trial registration This study had been prospectively registered with the Chinese Clinical Trials Registry. registration number: ChiCTR1900025907 at September 14, 2019.

Mechanosensory and mechanotransductive processes mediated by ion channels in articular chondrocytes: Potential therapeutic targets for osteoarthritis

“…More research is needed to define the electrophysiological properties of individual ion channels that can participate in mechanically altered metabolism of chondrocytes. The molecular mechanisms by which mechanical stimuli prevent articular cartilage degeneration and promote articular cartilage repair may yield insights into the rationale of possible mechanical therapy, such as the potential for therapeutic low-intensity pulsed ultrasound for OA [ 169 , 170 ].…”

Low-intensity ultrasound combined with allogenic adipose-derived mesenchymal stem cells (AdMSCs) in radiation-induced skin injury treatment

“…Based on acoustic pressure equations and t the effective radiation area (ERA) of the probe, the interference of the acoustic waves in the environment was modeled. The texture characteristics are including density, speed of sound and attenuation coefficient with 993.37 kg/m 3 , 1528 m/s and 0.025 Np/m MHz in water 37 °C and 1090 kg/m 3 , 1615 m/s, 4.02 Np/m.MHz in skin tissue 35–37 °C, respectively 17 . Then based on the wave interference scheme, the axial transverse profiles of the acoustic pressure in the resulting cylindrical coordinates are solved in programming FORTRAN (Intel Visual Fortran Composer XE 2011) With PC with Core i5-4200 MCPU-2.50 GHz–6 GB RAM.…”

“…Furthermore, it is necessary to examine the function of the ultrasound to be able to approach the therapeutic goals and reach an ideal knowledge of ultrasound function. The mechanical index represents the threshold for acoustic cavitation 17 – 19 . Since ionizing radiation delays the production of inflammatory cytokines in the skin tissue and reduces the healing period of damage, in this study, stem cells were used along with ultrasound waves to enhance the cumulative effect of the therapy procedure.…”

Current and novel theranostic modalities for knee osteoarthritis

“…They demonstrated that MSCs can effectively accelerate the repair of cartilage defects [96]. Numerous clinical trials [97][98][99][100][101][102][103][104][105] have been performed in this field that some of them mentioned in Table.…”