"Short Telomeres in ESCs Lead to Unstable Differentiation"

The ability to maintain telomere length is one of the many attributes of embryonic stem cells (ESCs) (Huang et al). Comprising of reverse transcriptase (Tert) and RNA template (Terc), telomerase mediates the addition of new telomeric DNA to the end of chromosomes which is required for ESC function (Agarwal et al, Batista et al and Marion et al) and also for iPSC generation (Marion et al). Previous studies have found that ESCs from late generation Terc -/- mice have short telomeres and have a reduced teratoma formation ability (Huang et al); and now the group of Lea Harrington at the Wellcome Trust Centre for Cell Biology and Institute of Cell Biology, The University of Edinburgh, Scotland have found that mice with critically short telomeres do not undergo stable differentiation, which the group have linked to alterations in pluripotency-associated gene expression and genome wide epigenetic alterations (Pucci et al).

"Medial ganglionic eminence–like cells derived from human embryonic stem cells correct learning and memory deficits"

Functionality of basal forebrain cholinergic neurons (BFCNs) and γ-aminobutyric acid (GABA) interneurons, derived from medial ganglionic eminence (MGE) (Sussel et al), are linked to learning and memory, and the ability to produce human MGE-progenitors in sufficient quantities could aid research into development and dysfunction and also potentially allow their use in cell replacement therapies. Previous studies by the group of Su-Chun Zhang at the Waisman Center, University of Wisconsin, Madison, USA have described the differentiation of hESCs into a primitive neuroepithelial cell (Li et al and Pankratz et al) which gives rise to various types of neurons in response to specific sets of morphogens, and they now report on the derivation of MGE-like progenitors which can produce GABA interneurons and BFCNs after transplantation into mouse brain lesions which correct learning and memory deficits (Liu et al).

"A Simple and Scalable Process for the Differentiation of Retinal Pigment Epithelium From Human Pluripotent Stem Cells" and "Rapid and Efficient Directed Differentiation of Human Pluripotent Stem Cells Into Retinal Pigmented Epithelium"

The high prevalence of blindness caused by age-related macular degeneration (AMD) (Gehrs et al), due to damaged or dysfunctional retinal pigment epithelium (RPE) cells (Khandhadia et al) has led to the use of pluripotent stem cells to derive RPE for transplantation. Various studies have shown that RPE can be derived from human embryonic stem cells (hESCs) (Klimanskaya et al) and human induced pluripotent stem cells (hiPSCs) (Buchholz et al, Hirami et al, Meyer et al and Osakada et al) and a human clinical trial of hESC-RPE cell transplantation is currently under way (Schwartz et al). However, techniques used so far are problematic for large scale production of consistent high quality cells. Now in two studies published in Stem Cells Translational Medicine, advancements in differentiation protocols are presented. In the first study, researchers from the group of Donald J. Zack at the Johns Hopkins University School of Medicine Baltimore, Maryland, USA have described a less labour-intensive myosin inhibitor-mediated differentiation protocol which, after enrichment, leads to a highly pure population of cells which display many characteristics of native RPE cells (Maruotti et al). In the latter study researchers from the laboratories of Peter J. Coffey and Dennis O. Clegg at the Neuroscience Research Institute and the Center for the Study of Macular Degeneration at the University of California, Santa Barbara, USA describe their work into the modification of current protocols by the addition of retinal induction factors and other factors at specific times giving an increased efficiency of RPE derivation at earlier time points (Buchholz et al).

"Comparison of Drug and Cell-Based Delivery: Engineered Adult Mesenchymal Stem Cells Expressing Soluble Tumor Necrosis Factor Receptor II Prevent Arthritis in Mouse and Rat Animal Models"

Tumor necrosis factor-α (TNFα) is a cytokine that mediates normal homeostatic mammalian processes (Schaible et al and Wajant et al) but has been linked to the systemic autoimmune disease Rheumatoid Arthritis (RA), where a TNFα induced cytokine cascade causes inflammation and joint destruction. Blocking TNFα function would therefore seem a viable means to treat RA. Etanercept, a TNF receptor (TNFR) linked to the immunoglobin Fc fragment and two monoclonal antibodies, infliximab and adalimumab are three TNFα inhibitors approved in the United States (Mazza et al), while TNFα blockers certolizumab pegol and golimumab are also utilised (Wallis and Scallon et al). However, the necessity for systemic delivery leads to certain unwanted side-effects, and so site-specific drug action is being sought after. To this end, in a report in Stem Cells Translational Medicine, researchers led by Joseph D. Mosca at Osiris Therapeutics, Inc., Baltimore, Maryland, USA have published the results of their studies on the potential use of mesenchymal stem cell (MSC)-based TNFR delivery and the efficacy of this treatment compared to the use of etanercept (Liu et al).

"Autocrine signaling based selection of combinatorial antibodies that transdifferentiate human stem cells"

The group of Richard A. Lerner at The Scripps Research Institute, La Jolla, CA have previously described a means of expressing antibodies through lentiviral infection of cells and studying how the cells are affected in an autocrine manner (Zhang et al) through interactions with membrane bound co-expressed receptors. In a recent report in PNAS they now describe a co-expression system of an antibody library with the granulocyte colony-stimulating factor receptor (G-CSFR), and have isolated agonist antibodies which can transdifferentiate human CD34+ haematopoietic stem cells (HSCs) into neural progenitor cells (NPCs) (Xie et al).