To provide a systematic review of the clinical literature reporting the efficacy of mesenchymal stem cells (MSCs) in terms of clinical outcomes including pain and function and cartilage repair in ...patients with osteoarthritis.
We systematically reviewed any studies investigating clinical outcomes and cartilage repair after the clinical application of cell populations containing MSCs in human subjects with knee osteoarthritis through MEDLINE, EMBASE, the Cochrane Library, CINAHL, Web of Science, and Scopus. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Studies with a level of evidence of IV or V were excluded. Methodological quality was assessed using the Modified Coleman Methodology Score. Clinical outcomes were assessed using clinical scores, and cartilage repair was assessed using magnetic resonance imaging and second-look arthroscopy findings.
A total of 17 studies that met the criteria of 50 full-text studies were included in this review, with 6 randomized controlled trials, 8 prospective observational studies, and 3 retrospective case-control studies. Among 17 studies, 8 studies used bone marrow–derived MSCs, 6 used adipose tissue–derived stromal vascular fraction, 2 used adipose tissue–derived MSCs, and 1 used umbilical cord blood–derived MSCs. All studies except 2 reported significantly better clinical outcomes in the MSC group or improved clinical outcomes at final follow-up. In terms of cartilage repair, 9 of 11 studies reported improvement of the cartilage state on magnetic resonance imaging, and 6 of 7 studies reported repaired tissue on second-look arthroscopy. The mean Modified Coleman Methodology Score was 55.5 ± 15.5 (range, 28-74).
Intra-articular MSCs provide improvements in pain and function in knee osteoarthritis at short-term follow-up (<28 months) in many cases. Some efficacy has been shown of MSCs for cartilage repair in osteoarthritis; however, the evidence of efficacy of intra-articular MSCs on both clinical outcomes and cartilage repair remains limited.
Level III; systematic review of level I, II, and III studies.
Despite the high prevalence and functional significance of nonregular assemblies in biology, little attention has been given to realize them in artificial systems. Here, the discovery of general ...principles underlying the formation of nonregular objects is described by chemical self‐assembly. The cell‐shaped assemblies (CSAs) are characterized by a main body comprising a nonregular vesicle and dendritically shaped spiky projections. The major mechanisms of CSA morphogenesis are: first, polycrystalline structures consisting of grains and grain boundaries induce the formation of nonregular objects by promoting nonuniform supramolecular crystal growth. Second, the fibrous nanostructures in 2D networks and in 1D bundles firmly support the main body and the spiky projections, respectively. This study also shows that there exist certain connections among entirely disparate entities, that is, organic supramolecular assemblies, inorganic materials, and cells regarding their fundamental principles of building block organizations. The principle behind the CSA formation can be applied to control the dynamic and mechanical properties of self‐assembled materials.
Cell‐shaped assemblies represent complex artificial materials with nonregular ultrastructural ordering similar to many natural and biological objects. Rather than simple coassembly, heterotypic assembly is defined as the combination of coassembly and self‐sorting. Heterotypic assembly with polycrystalline 2D grain formation of peptide building blocks enables the formation of complex cell‐shaped objects.
Self-assembling peptides are biomedical materials with unique structures that are formed in response to various environmental conditions. Governed by their physicochemical characteristics, the ...peptides can form a variety of structures with greater reactivity than conventional non-biological materials. The structural divergence of self-assembling peptides allows for various functional possibilities; when assembled, they can be used as scaffolds for cell and tissue regeneration, and vehicles for drug delivery, conferring controlled release, stability, and targeting, and avoiding side effects of drugs. These peptides can also be used as drugs themselves. In this review, we describe the basic structure and characteristics of self-assembling peptides and the various factors that affect the formation of peptide-based structures. We also summarize the applications of self-assembling peptides in the treatment of various diseases, including cancer. Furthermore, the in-cell self-assembly of peptides, termed reverse self-assembly, is discussed as a novel paradigm for self-assembling peptide-based nanovehicles and nanomedicines.
Background:
Although platelet-rich plasma (PRP) has potential as a regenerative treatment for knee osteoarthritis, its efficacy varies. Compositional differences among types of PRP could affect ...clinical outcomes, but the biological characterization of PRP is lacking.
Purpose:
To assess the efficacy of intra-articular PRP injection in knee osteoarthritis as compared with hyaluronic acid (HA) injection and to determine whether the clinical efficacy of PRP is associated with its biological characteristics.
Study Design:
Randomized controlled trial; Level of evidence, 1.
Methods:
A total of 110 patients with symptomatic knee osteoarthritis received a single injection of leukocyte-rich PRP (1 commercial kit) or HA. Clinical data were assessed at baseline and at 6 weeks and 3 and 6 months after injection. The primary endpoint was an improvement in the International Knee Documentation Committee (IKDC) subjective score at 6 months, and the secondary endpoints were improvements in scores based on the Patient Global Assessment, the visual analog scale (VAS) for pain, the Western Ontario and McMaster Universities Osteoarthritis Index, and the Samsung Medical Center patellofemoral score. Cell counts and concentrations of growth factors and cytokines in the injected PRP were assessed to determine their association with clinical outcomes.
Results:
PRP showed significantly improvement in IKDC subjective scores at 6 months (11.5 in the PRP group vs 6.3 in the HA group; P = .029). There were no significant differences between groups in other clinical outcomes. The Patient Global Assessment score at 6 months was better in the PRP group (P = .035). The proportion of patients who scored above the minimal clinically important difference (MCID) for VAS at 6 months was significantly higher in the PRP group (P = .044). Within the PRP group, the concentrations of platelet-derived growth factors were high in patients with a score above the MCID for VAS at 6 months. The incidence of adverse events did not differ between the groups (P > .05).
Conclusion:
PRP had better clinical efficacy than HA. High concentrations of growth factors were observed in patients who scored above the MCID for clinical outcomes in the PRP group. These findings indicate that concentration of growth factors needs to be taken into consideration for future investigations of PRP in knee osteoarthritis.
Registration:
NCT02211521 (ClinicalTrials.gov identifier).
•Fucoidan was successfully depolymerized using SCW treatment.•BBD was used to find the best conditions of antioxidant and chemical composition of fucoidan.•The best conditions was found to be 214 °C, ...40 bar, 60 mL/g, 223 RPM and 5 min.•Low molecular weight of fucoidan was obtained from SCW treatment.•The optimized condition showed improved biological activities from native fucoidan.
Fucoidan is a marine sulfated polysaccharide that possesses various biological activities. To enhance the functional properties of fucoidan, it was depolymerized using a green technique viz. subcritical water treatment (SCW) to produce a low molecular weight fucoidan. In this study, response surface methodology (RSM) was used to study the influence of different influences for instance temperature, pressure, liquid to solid ratio, and agitation speed to depolymerize fucoidan. RSM was used to focus on the antioxidant activity and chemical composition of SCW-treated fucoidan. Further, resulting SCW-treated fucoidan was investigated by UV-Vis, FT-IR, Thermal gravimetric analysis (TGA), DSC, Elemental analysis, and ESI-MS. Moreover, the optimized SCW-treated fucoidan was checked for cytotoxicity, antimicrobial, antidiabetic, and anticoagulant activity compared with the untreated fucoidan. The obtained values displayed that SCW treatment breakdowns polymer chain and so it produces low molecular weight fucoidan. Biological activities were improved as the molecular weight was reduced.
•Growth rate, removal of N, P and organic carbon by C. sorokiniana were evaluated.•The microalgae cultured under autotrophic, heterotrophic and mixotrophic conditions.•The growth rate and removal ...rates of N, P was significant in heterotrophic condition.•Heterotrophic condition was superior compared to other conditions.•Heterotrophic condition would be useful for application in wastewater treatment.
This study sought to investigate the growth rate and organic carbon and nutrient removal efficiency of Chlorella sorokiniana under autotrophic, heterotrophic and mixotrophic conditions. Growth rates of the microalgae were 0.24d−1, 0.53d−1 and 0.44d−1 in autotrophic, heterotrophic and mixotrophic conditions, respectively. The growth rate of C. sorokiniana was significantly higher for that grown under heterotrophic conditions. The nitrogen removal rates were 13.1mg-N/L/day, 23.9mg-N/L/day and 19.4mg-N/L/day, respectively. The phosphorus removal rates reached to 3.4mg-P/L/day, 5.6mg-P/L/day and 5.1mg-P/L/day, respectively. Heterotrophic conditions were superior in terms of the microalgae growth and removal of nitrogen and phosphorus compared to autotrophic and mixotrophic conditions, suggesting that microalgae cultured under this condition would be most useful for application in wastewater treatment systems.
Background:
Although many clinical studies have assessed the efficacy of mesenchymal stem cells (MSCs) in knee osteoarthritis, evidence on their efficacy remains unclear owing to heterogeneity of ...cell entity and concomitant procedures.
Purpose:
To determine the efficacy of culture-expanded MSCs in knee osteoarthritis in terms of clinical outcome and cartilage repair via meta-analysis of randomized controlled trials (RCTs) without adjuvant surgery.
Study Design:
Meta-analysis.
Methods:
PubMed, Embase, the Cochrane Library, CINAHL, and Scopus were searched from inception to December 31, 2018. RCTs with culture-expanded MSCs for treating knee osteoarthritis were included. Studies with adjuvant surgery or cell concentrate were excluded. Quality was assessed by the Cochrane Collaboration risk-of-bias tool. For meta-analysis, data on clinical outcomes were measured using a visual analog scale (VAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and data on cartilage repair were measured using the Whole-Organ Magnetic Resonance Imaging Score (WORMS); categorization related to improvement was extracted.
Results:
Six RCTs (203 patients) were included. Two studies were deemed to have a low risk of bias. In pooled analysis, the only significant difference was in the VAS score (mean difference, –13.55; 95% CI, –22.19 to −4.9). In cumulative pain analysis with VAS and WOMAC pain scores, there was significant improvement after treatment (standardized mean difference, –0.54; 95% CI, –0.85 to −0.23). There was no significant difference in cartilage repair assessed by magnetic resonance imaging (standardized mean difference, 0.11; 95% CI, –0.51 to 0.73), WORMS (standardized mean difference, 1.68; 95% CI −14.84 to 18.21), or categorical results (odds ratio, 1.56; 95% CI, 0.32-7.59).
Conclusion:
Intra-articular injection of culture-expanded MSCs without adjuvant surgery can improve pain for patients experiencing knee osteoarthritis at short-term follow-up (6-12 months). However, evidence regarding function and cartilage repair remains limited.
ABSTRACT
Objectives
We investigated whether systemic immune‐inflammation index (SII) at diagnosis can estimate the cross‐sectional high activity and predict the poor outcomes in immunosuppressive ...drug‐naïve patients with antineutrophil cytoplasmic antibody‐associated vasculitis (AAV).
Methods
We retrospectively reviewed the medical records of 163 patients with AAV and obtained clinical and laboratory data. We calculated Birmingham vasculitis activity score (BVAS) as well as five‐factor score (FFS) (2009) at diagnosis. SII at diagnosis was calculated by the equation of (SII at diagnosis = platelet count × neutrophil count/lymphocyte count at diagnosis). Severe AAV was defined as BVAS at diagnosis ≥16. The odds ratio was assessed using the multivariable logistic regression analysis and cumulative survival rates were compared by the Kaplan–Meier survival analysis.
Results
The median age at diagnosis was 58.0 years old and 51 patients were men. The median BVAS was 12.0. Fifty‐seven patients had severe AAV. The median SII at diagnosis was 1349.6. In the multivariable analysis, only SII exhibited a significant odds ratio for the cross‐sectional severe AAV (P = 0.043). We obtained the cut‐off of SII at diagnosis for severe AAV as 1573.56. Patients with SII at diagnosis ≥1573.56 exhibited a significantly high relative risk of the cross‐sectional severe AAV compared to those without (relative risk 4.625). Furthermore, patients with SII at diagnosis ≥1573.56 exhibited significantly the lower cumulative relapse free and renal survivals than those without.
Conclusion
Systemic immune‐inflammation index at diagnosis could estimate the cross‐section severe AAV and predict the poor outcomes in AAV patients.
Summary at a Glance
The study shows that the systemic immune‐inflammation index at diagnosis can estimate disease activity and predict the outcomes of patients with antineutrophil cytoplasmic antibody‐associated vasculitis.
We have developed RGD-attached gold (Au) half-shell nanoparticles containing methotrexate (MTX) for the treatment of rheumatoid arthritis (RA), where MTX is the most widely used disease-modifying ...anti-rheumatic drug (DMARD) for the treatment of RA, and RGD peptide is a targeting moiety for inflammation. Upon near-infrared (NIR) irradiation, heat is locally generated due to Au half-shells, and the drug release rate is enhanced, delivering heat and drug to the inflamed joints simultaneously. RA is a chronic inflammatory disease characterized by synovial inflammation in multiple joints within the penetration depth of NIR light. When combined with NIR irradiation, these nanoparticles containing a much smaller dosage of MTX (1/930 of MTX solution) showed greater therapeutic effects than that of a conventional treatment with MTX solution in collagen-induced arthritic mice. This novel drug delivery system is a good way to maximize therapeutic efficacy and minimize dosage-related MTX side effects in the treatment of RA. Furthermore, these multifunctional nanoparticles could be applied to other DMARDs for RA or other inflammatory diseases.
Abstract We have developed methotrexate (MTX)-loaded poly(lactic- co -glycolic acid, PLGA) gold (Au)/iron (Fe)/gold (Au) half-shell nanoparticles conjugated with arginine-glycine-aspartic acid (RGD), ...which can be applied for magnetic targeted chemo-photothermal treatment, and in vivo multimodal imaging of rheumatoid arthritis (RA). Upon near-infrared (NIR) irradiation, local heat is generated at the inflammation region due to the NIR resonance of Au half-shells and MTX release from PLGA nanoparticles is accelerated. The Fe half-shell layer embedded between the Au half-shell layers enables in vivo T 2 -magnetic resonance (MR) imaging in addition to NIR absorbance imaging. Furthermore, the delivery of the nanoparticles to the inflammation region in collagen-induced arthritic (CIA) mice, and their retention can be enhanced under external magnetic field. When combined with consecutive NIR irradiation and external magnetic field application, these nanoparticles provide enhanced therapeutic effects with an MTX dosages of only 0.05% dosage compared to free MTX therapy for the treatment of RA.
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