Linked Patient-Reported Outcomes Data From Patients With Multiple Sclerosis Recruited on an Open Internet Platform to Health Care Claims Databases Identifies a Representative Population for Real-Life Data Analysis in Multiple Sclerosis.

BACKGROUND: An enormous amount of information relevant to public health is being generated directly by online communities. OBJECTIVE: To explore the feasibility of creating a dataset that links patient-reported outcomes data, from a Web-based survey of US patients with multiple sclerosis (MS) recruited on open Internet platforms, to health care utilization information from health care claims databases. The dataset was generated by linkage analysis to a broader MS population in the United States using both pharmacy and medical claims data sources. METHODS: US Facebook users with an interest in MS were alerted to a patient-reported survey by targeted advertisements. Eligibility criteria were diagnosis of MS by a specialist (primary progressive, relapsing-remitting, or secondary progressive), ≥12-month history of disease, age 18-65 years, and commercial health insurance. Participants completed a questionnaire including data on demographic and disease characteristics, current and earlier therapies, relapses, disability, health-related quality of life, and employment status and productivity. A unique anonymous profile was generated for each survey respondent. Each anonymous profile was linked to a number of medical and pharmacy claims datasets in the United States. Linkage rates were assessed and survey respondents' representativeness was evaluated based on differences in the distribution of characteristics between the linked survey population and the general MS population in the claims databases. RESULTS: The advertisement was placed on 1,063,973 Facebook users' pages generating 68,674 clicks, 3719 survey attempts, and 651 successfully completed surveys, of which 440 could be linked to any of the claims databases for 2014 or 2015 (67.6% linkage rate). Overall, no significant differences were found between patients who were linked and not linked for educational status, ethnicity, current or prior disease-modifying therapy (DMT) treatment, or presence of a relapse in the last 12 months. The frequencies of the most common MS symptoms did not differ significantly between linked patients and the general MS population in the databases. Linked patients were slightly younger and less likely to be men than those who were not linkable. CONCLUSIONS: Linking patient-reported outcomes data, from a Web-based survey of US patients with MS recruited on open Internet platforms, to health care utilization information from claims databases may enable rapid generation of a large population of representative patients with MS suitable for outcomes analysis.

Human periosteum is a source of cells for orthopaedic tissue engineering: a pilot study.

BACKGROUND: Periosteal cells are important in embryogenesis, fracture healing, and cartilage repair and could provide cells for osteochondral tissue engineering. QUESTIONS/PURPOSE: We determined whether a population of cells isolated from human periosteal tissue contains cells with a mesenchymal stem cell (MSC) phenotype and whether these cells can be expanded in culture and used to form tissue in vitro. METHODS: We obtained periosteal tissue from six patients. Initial expression of cell surface markers was assessed using flow cytometry. Cells were cultured over 10 generations and changes in gene expression evaluated to assess phenotypic stability. Phenotype was confirmed using flow cytometry and colony-forming ability assays. Mineral formation was assessed by culturing Stro-1(-) and unsorted cells with osteogenic supplements. Three cell culture samples were used for a reverse transcription-polymerase chain reaction, four for flow cytometry, three for colony-forming assay, and three for mineralization. RESULTS: Primary cultures, containing large numbers of hematopoietic cells were replaced initially by Stro-1 and ALP-expressing immature osteoblastic cell types and later by ALP-expressing cells, which lacked Stro-1 and which became the predominant cell population during subculture. Approximately 10% of the total cell population continued to express markers for Stro1(+)/ALP(-) cells throughout. CONCLUSIONS: These data suggest periosteum contains a large number of undifferentiated cells that can differentiate into neotissue and persist despite culture in noncell-specific media for over 10 passages. CLINICAL RELEVANCE: Cultured periosteal cells may contribute to tissue formation and may be applicable for tissue engineering applications.

Identification of rare progenitor cells from human periosteal tissue using droplet microfluidics.

The isolation and characterisation of single cells from a heterogeneous population are important processes in cell biology, immunology, stem cell research, and cancer research. In the development of novel cell-based therapies, there is a considerable need to target specific cell types to allow for further analysis and amplification ex vivo. We introduce, herein, the use of droplet-based microfluidics as a platform technology for the identification and quantification of distinct cell phenotypes. Using molecular labelling of specific cell populations by antibodies and fluorescent dyes, detection of single cells encapsulated within picolitre-sized aqueous droplets can be performed using high-sensitivity confocal fluorescence detection. Specifically, rare progenitor cells were immunodetected within a heterogeneous population of cells isolated from human periosteal tissue. Using this model human cell population, the accuracy and reproducibility of the droplet system were tested and the results were verified using conventional flow cytometry. It was found that the quantitation of phenotypic subpopulations measured using both techniques is directly comparable. Accordingly, this study demonstrates the biological capacity of droplet-based microfluidics for cellular analysis and provides a necessary first step towards the development of a novel cell sorting technology.

Novel materials for bone and cartilage regeneration.

Materials that enhance bone and cartilage regeneration promise to be valuable in both research and clinical applications. Both natural and synthetic polymers can be used to create scaffolds that support cells and incorporate cues which guide tissue repair. Recently, electrospinning, peptide self-assembly and biomineralisation have been employed to fabricate nanostructured scaffolds that better mimic the complex extracellular environment found within tissues, in vivo. The incorporation of peptide motifs recognised by cell receptors and the use of recombinant DNA technology have enabled the creation of scaffolds with new levels of biofunctionality. Advances in materials design will enhance our ability to create highly tailored cellular environments for bone and cartilage regeneration.

Synthesis of two-component injectable polyurethanes for bone tissue engineering.

The advent of injectable polymer technologies has increased the prospect of developing novel, minimally invasive arthroscopic techniques to treat a wide variety of ailments. In this study, we have synthesised and evaluated a novel polyurethane-based injectable, in situ curable, polymer platform to determine its potential uses as a tissue engineered implant. Films of the polymers were prepared by reacting two pentaerythritol-based prepolymers, and characterised for mechanical and surface properties, and cytocompatibility. This polymer platform displayed mechanical strength and elasticity superior to many injectable bone cements and grafts. Cytotoxicity tests using primary human osteoblasts, revealed positive cell viability and increased proliferation over a period of 7 days in culture. This favourable cell environment was attributed to the hydrophilic nature of the films, as assessed by dynamic contact angle (DCA) analysis of the sample surfaces. The incorporation of beta-TCP was shown to improve mechanical properties, surface wettability, and cell viability and proliferation, compared to the other sample types. SEM/EDX analysis of these surfaces also revealed physicochemical surface heterogeneity in the presence of beta-TCP. Based on preliminary mechanical analysis and cytotoxicity results, these injectable polymers may have a number or potential orthopaedic applications; ranging from bone glues to scaffolds for bone regeneration.