Human Skin Keratinocytes Can Be Reprogrammed to Express Neuronal Genes and Proteins After a Single Treatment With Decitabine.

Human skin keratinocytes can be reprogrammed to express neuronal genes and proteins after a single treatment with decitabine.

Biores Open Access. 2013 Jun; 2(3): 217-21
Bickenbach JR, Tomanek-Chalkley A, Wiechert S, Winter MC

Patient-specific cell replacement therapy is fast becoming the future of medicine, requiring safe, effective methods for reprogramming a patient’s own cells. Previously, we showed that a single transient transfection with a plasmid encoding Oct4 was sufficient to reprogram human skin keratinocytes (HSKs), and that this transfection resulted in a decrease in global DNA methylation. In more recent work we showed that decreasing global DNA methylation using the U.S. Food and Drug Administration-approved cancer treatment drug decitabine was sufficient to induce expression of endogenous Oct4. Here we report that a single treatment with decitabine, followed by 5 days in a defined neuronal transformation medium, then 7 days in a neuronal maintenance medium is sufficient to convert HSKs into cells that change their morphology substantially, gain expression of neuronal markers, and lose expression of keratinocyte markers. Within 1 week of treatment the cells express mRNA for ?3-tubulin and doublecortin, and at the end of 2 weeks express mRNA for NeuN, FOXP2, and NCAM1. Additionally, at the end of this protocol, neurofilament-1, nestin, synapsin, FOXP2, and GluR1 proteins are detectable by immunostaining. Thus, we demonstrate a simple method that begins the process for producing cells for cell replacement therapies without using exogenously introduced DNA. HubMed – drug


Developing a Prototype System for Integrating Pharmacogenomics Findings into Clinical Practice.

J Pers Med. 2012 Nov 20; 2(4): 241-256
Overby CL, Tarczy-Hornoch P, Kalet IJ, Thummel KE, Smith JW, Fiol GD, Fenstermacher D, Devine EB

Findings from pharmacogenomics (PGx) studies have the potential to be applied to individualize drug therapy to improve efficacy and reduce adverse drug events. Researchers have identified factors influencing uptake of genomics in medicine, but little is known about the specific technical barriers to incorporating PGx into existing clinical frameworks. We present the design and development of a prototype PGx clinical decision support (CDS) system that builds on existing clinical infrastructure and incorporates semi-active and active CDS. Informing this work, we updated previous evaluations of PGx knowledge characteristics, and of how the CDS capabilities of three local clinical systems align with data and functional requirements for PGx CDS. We summarize characteristics of PGx knowledge and technical needs for implementing PGx CDS within existing clinical frameworks. PGx decision support rules derived from FDA drug labels primarily involve drug metabolizing genes, vary in maturity, and the majority support the post-analytic phase of genetic testing. Computerized provider order entry capabilities are key functional requirements for PGx CDS and were best supported by one of the three systems we evaluated. We identified two technical needs when building on this system, the need for (1) new or existing standards for data exchange to connect clinical data to PGx knowledge, and (2) a method for implementing semi-active CDS. Our analyses enhance our understanding of principles for designing and implementing CDS for drug therapy individualization and our current understanding of PGx characteristics in a clinical context. Characteristics of PGx knowledge and capabilities of current clinical systems can help govern decisions about CDS implementation, and can help guide decisions made by groups that develop and maintain knowledge resources such that delivery of content for clinical care is supported. HubMed – drug


Exploration on the safety assessment of nanomaterials in China.

Interface Focus. 2012 Jun 6; 2(3): 387-92
Shi XL, Wang Q, Hu K, Wang XM

More and more applications of nanomaterials have been achieved in the biomedicine field. Numerous nanomedical devices, such as bone grafts with nano-hydroxyapatite and the silver-based anti-bacteria products, have been developed and have been trying to enter into the Chinese market. The State Food and Drug Administration of China (SFDA) is facing a critical challenge of how to explore and supervise the safety assessment of the nanomedical products. This paper briefly introduces the approval status of nanomedical products and the current advances of the safety assessment of nanomaterials in China. HubMed – drug


Peptide- and saccharide-conjugated dendrimers for targeted drug delivery: a concise review.

Interface Focus. 2012 Jun 6; 2(3): 307-24
Liu J, Gray WD, Davis ME, Luo Y

Dendrimers comprise a category of branched materials with diverse functions that can be constructed with defined architectural and chemical structures. When decorated with bioactive ligands made of peptides and saccharides through peripheral chemical groups, dendrimer conjugates are turned into nanomaterials possessing attractive binding properties with the cognate receptors. At the cellular level, bioactive dendrimer conjugates can interact with cells with avidity and selectivity, and this function has particularly stimulated interests in investigating the targeting potential of dendrimer materials for the design of drug delivery systems. In addition, bioactive dendrimer conjugates have so far been studied for their versatile capabilities to enhance stability, solubility and absorption of various types of therapeutics. This review presents a brief discussion on three aspects of the recent studies to use peptide- and saccharide-conjugated dendrimers for drug delivery: (i) synthesis methods, (ii) cell- and tissue-targeting properties and (iii) applications of conjugated dendrimers in drug delivery nanodevices. With more studies to elucidate the structure-function relationship of ligand-dendrimer conjugates in transporting drugs, the conjugated dendrimers hold promise to facilitate targeted delivery and improve drug efficacy for discovery and development of modern pharmaceutics. HubMed – drug


Mesoporous bioactive glasses: structure characteristics, drug/growth factor delivery and bone regeneration application.

Interface Focus. 2012 Jun 6; 2(3): 292-306
Wu C, Chang J

The impact of bone diseases and trauma in the whole world has increased significantly in the past decades. Bioactive glasses are regarded as an important bone regeneration material owing to their generally excellent osteoconductivity and osteostimulativity. A new class of bioactive glass, referred to as mesoporous bioglass (MBG), was developed 7 years ago, which possess a highly ordered mesoporous channel structure and a highly specific surface area. The study of MBG for drug/growth factor delivery and bone tissue engineering has grown significantly in the past several years. In this article, we review the recent advances of MBG materials, including the preparation of different forms of MBG, composition-structure relationship, efficient drug/growth factor delivery and bone tissue engineering application. By summarizing our recent research, the interaction of MBG scaffolds with bone-forming cells, the effect of drug/growth factor delivery on proliferation and differentiation of tissue cells and the in vivo osteogenesis of MBG scaffolds are highlighted. The advantages and limitations of MBG for drug delivery and bone tissue engineering have been compared with microsize bioactive glasses and nanosize bioactive glasses. The future perspective of MBG is discussed for bone regeneration application by combining drug delivery with bone tissue engineering and investigating the in vivo osteogenesis mechanism in large animal models. HubMed – drug