Self-Assembling Proteins as High-Performance Substrates for Embryonic Stem Cell Self-Renewal.

The development of extracellular matrix mimetics that imitate niche stem cell microenvironments and support cell growth for technological applications is intensely pursued. Specifically, mimetics are sought that can enact control over the self-renewal and directed differentiation of human pluripotent stem cells (hPSCs) for clinical use. Despite considerable progress in the field, a major impediment to the clinical translation of hPSCs is the difficulty and high cost of large-scale cell production under xeno-free culture conditions using current matrices. Here, a bioactive, recombinant, protein-based polymer, termed ZTFn , is presented that closely mimics human plasma fibronectin and serves as an economical, xeno-free, biodegradable, and functionally adaptable cell substrate. The ZTFn substrate supports with high performance the propagation and long-term self-renewal of human embryonic stem cells while preserving their pluripotency. The ZTFn polymer can, therefore, be proposed as an efficient and affordable replacement for fibronectin in clinical grade cell culturing. Further, it can be postulated that the ZT polymer has significant engineering potential for further orthogonal functionalization in complex cell applications.

Coenzyme Q10 supplementation reduces oxidative stress and decreases antioxidant enzyme activity in children with autism spectrum disorders.

Antioxidants and oxidative stress can participate in pathobiochemical mechanisms of autism spectrum disorders (ASDs). The aim was to identify the effects of early CoQ10 supplementation on oxidative stress in children with ASDs. Ninety children with ASDs were included in this study, based on DSM-IV criteria and using Childhood Autism Rating Scale (CARS) scores. Concentrations of CoQ10, MDA, total antioxidant status (TAS) assay, and antioxidant enzymes (superoxide dismutase or SOD and glutathione peroxidase or GPx) activity were determined in serum before and after 100 days of supportive therapy with CoQ10 at daily doses of 30 and 60 mg. Data on children's behavior were collected from parents and babysitters. CoQ10 supportive therapy was determined after three months with daily dose 2 ͯ 30 mg improved oxidative stress in the children with ASDs. A relation was seen between serum MDA (r2 = 0.668) and TAS (r2 = 0.007), and antioxidant enzymes (SOD [r2 = 0.01] and GPx [r2 = 0.001]) activity and CARS score. Based on the results, high doses of CoQ10 can improve gastrointestinal problems (P = 0.004) and sleep disorders (P = 0.005) in children with ASDs with an increase in the CoQ10 of the serum. We concluded that the serum concentration of CoQ10 and oxidative stress could be used as relevant biomarkers in helping the improvement of ASDs.

Increased Serum Levels of Tumor Necrosis Factor-Alpha, Resistin, and Visfatin in the Children with Autism Spectrum Disorders: A Case-Control Study.

Background. Autism spectrum disorders (ASDs) are complex disorders where the pathogenesis is not fully understood. Several proinflammatory and immunoinflammatory disturbances have been observed in the etiology of ASD. There is, however, limited knowledge on variations of adipokines in ASD. The present study aimed to analyze the serum levels of resistin, visfatin, and tumor necrosis factor-alpha (TNF-α) in children with ASD in relation to body weight, gender, and ASD severity level. Method. In total, 30 children with ASD (mean age: 7.72 ± 2.65 y; range; 4-12 y) and 30 healthy children (mean age: 8.4 ± 2.66 y; range: 4-12 y), including males and females, were matched for age, gender, and body mass index (BMI). Serum samples were collected, and visfatin, resistin, and TNF-α serum levels were measured using an enzyme-linked immunosorbent assay (ELISA) kit. Result. Serum visfatin, resistin, and TNF-α levels in children with ASD were significantly higher than that in the healthy patients (p < 0.05). Two significant correlations were found: a correlation between resistin and visfatin with TNF-α in children with ASD (R = 0.8 and R = 0.62, resp.) and a correlation between resistin and visfatin in children with ASD (R = 0.66). Conclusion. Higher TNF-α, resistin, and visfatin levels were found in children with ASD in comparison with controls, suggesting that elevated levels of serum proinflammatory agents may be implicated in the pathophysiology of ASD.

Current Biosafety Considerations in Stem Cell Therapy.

Stem cells can be valuable model systems for drug discovery and modelling human diseases as well as to investigate cellular interactions and molecular events in the early stages of development. Controlling the differentiation of stem cells into specific germ layers provides a potential source of highly specialized cells for therapeutic applications. In recent years, finding individual properties of stem cells such as their ultimate self-renewal capacity and the generation of particular cell lines by differentiation under specific culture conditions underpins the development of regenerative therapies. These futures make stem cells a leading candidate to treat a wide range of diseases. Nevertheless, as with all novel treatments, safety issues are one of the barriers that should be overcome to guarantee the quality of a patient's life after stem cell therapy. Many studies have pointed to a large gap in our knowledge about the therapeutic applications of these cells. This gap clearly shows the importance of biosafety concerns for the current status of cell-based therapies, even more than their therapeutic efficacy. Currently, scientists report that tumorigenicity and immunogenicity are the two most important associated cell-based therapy risks. In principle, intrinsic factors such as cell characteristics and extrinsic elements introduced by manufacturing of stem cells can result in tumor formation and immunological reactions after stem cell transplantation. Therapeutic research shows there are many biological questions regarding safety issues of stem cell clinical applications. Stem cell therapy is a rapidly advancing field that needs to focus more on finding a comprehensive technology for assessing risk. A variety of risk factors (from intrinsic to extrinsic) should be considered for safe clinical stem cell therapies.