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To determine if patients with post-polio syndrome (PPS) show spinal cord gray matter (SCGM) atrophy and to assess associations between SCGM atrophy, muscle strength and patient-reported functional decline.Twenty patients diagnosed with PPS (March of Dimes criteria) and 20 age- and sex-matched healthy controls (HC) underwent 3T axial 2D-rAMIRA magnetic resonance imaging at the intervertebral disc levels C2/C3-C6/C7, T9/T10 and the lumbar enlargement level (TPost-polio syndrome patients showed significantly and preferentially reduced SCGM areas at C2/C3 (p = 0.048), C3/C4 (p = 0.001), C4/C5 (p 0.001), C5/C6 (p = 0.004) and TPatients with PPS show significant SCGM atrophy that correlates with muscle strength and is associated with PPS-related functional decline. Our findings suggest a secondary neurodegenerative process underlying SCGM atrophy in PPS that is not explained by aging or residua of the initial infection alone. Confirmation by longitudinal studies is needed. The described imaging methodology is promising for developing novel imaging surrogates for SCGM diseases.

Severe persistent pruritus is a common, but incompletely characterized, complication of hydroxyethyl starch (HES) infusion. This retrospective study aimed to assess HES-induced pruritus by electron microscopic findings, pruritus characteristics, and response to stimuli, and to determine the impact of HES dosage, molecular weight and substitution. Seventy patients with electron micro-scopy-proven HES-induced pruritus were included. HES-laden vacuoles were observed in skin macrophages of all patients. The median latency between HES exposure and pruritus onset was 3 weeks, and the median duration of pruritus was 6 months. Pruritus was severe, or very severe, in 80% of patients. Mechanical stimuli triggered pruritus in 74% of patients. Although the median cumulative dose of HES was 300 g, 15% of patients developed pruritus after only 30 g. There were no significant differences between HES 130/0.4 and HES 200/0.5 in pruritus latency, duration or severity. HES-induced pruritus thus may occur at any dose, molecular weight or substitution.

SummaryInduced pluripotent stem cells (iPSCs) outwardly appear to be indistinguishable from embryonic stem cells (ESCs). A study of gene expression profiles of mouse and human ESCs and iPSCs suggests that, while iPSCs are quite similar to their embryonic counterparts, a recurrent gene expression signature appears in iPSCs regardless of their origin or the method by which they were generated. Upon extended culture, hiPSCs adopt a gene expression profile more similar to hESCs; however, they still retain a gene expression signature unique from hESCs that extends to miRNA expression. Genome-wide data suggested that the iPSC signature gene expression differences are due to differential promoter binding by the reprogramming factors. High-resolution array profiling demonstrated that there is no common specific subkaryotypic alteration that is required for reprogramming and that reprogramming does not lead to genomic instability. Together, these data suggest that iPSCs should be considered a unique subtype of pluripotent cell.

The potential for directed differentiation of human-induced pluripotent stem (iPS) cells to functional postmitotic neuronal phenotypes is unknown. Following methods shown to be effective at generating motor neurons from human embryonic stem cells (hESCs), we found that once specified to a neural lineage, human iPS cells could be differentiated to form motor neurons with a similar efficiency as hESCs. Human iPS-derived cells appeared to follow a normal developmental progression associated with motor neuron formation and possessed prototypical electrophysiological properties. This is the first demonstration that human iPS-derived cells are able to generate electrically active motor neurons. These findings demonstrate the feasibility of using iPS-derived motor neuron progenitors and motor neurons in regenerative medicine applications and in vitro modeling of motor neuron diseases. Disclosure of potential conflicts of interest is found at the end of this article.

The derivation of germ cells from human embryonic stem cells (hESCs) or human induced pluripotent stem (hIPS) cells represents a desirable experimental model and potential strategy for treating infertility. In the current study, we developed a triple biomarker assay for identifying and isolating human primordial germ cells (PGCs) by first evaluating human PGC formation during the first trimester in vivo. Next, we applied this technology to characterizing in vitro derived PGCs (iPGCs) from pluripotent cells. Our results show that codifferentiation of hESCs on human fetal gonadal stromal cells significantly improves the efficiency of generating iPGCs. Furthermore, the efficiency was comparable between various pluripotent cell lines regardless of origin from the inner cell mass of human blastocysts (hESCs), or reprogramming of human skin fibroblasts (hIPS). To better characterize the iPGCs, we performed Real-time polymerase chain reaction, microarray, and bisulfite sequencing. Our results show that iPGCs at day 7 of differentiation are transcriptionally distinct from the somatic cells, expressing genes associated with pluripotency and germ cell development while repressing genes associated with somatic differentiation (specifically multiple HOX genes). Using bisulfite sequencing, we show that iPGCs initiate imprint erasure from differentially methylated imprinted regions by day 7 of differentiation. However, iPGCs derived from hIPS cells do not initiate imprint erasure as efficiently. In conclusion, our results indicate that triple positive iPGCs derived from pluripotent cells differentiated on hFGS cells correspond to committed first trimester germ cells (before 9 weeks) that have initiated the process of imprint erasure. Disclosure of potential conflicts of interest is found at the end of this article.

Adult stem cells are set aside during development in order to provide a source for replenishment of tissue over time in response to damage or simply wear and tear. The literature suggests that stem cells can be found in most major organ systems, and that they possess defining characteristics, namely the ability to both self-renew and differentiate down one or more specific lineages. Many groups have sought to define stem cell specific physiology in a molecular fashion by identifying those genes specifically expressed in stem cells. Although these data suggest that there are genes frequently found to be upregulated in stem cells from various tissues, they do not definitively demonstrate that these cells all function similarly. There is also considerable data showing how various signaling pathways influence stem cell growth and differentiation. A review of this literature suggests that many of the well-described pathways affect adult mammalian stem cells from different tissues similarly, and that these effects are sometimes unique to stem cells as opposed to their progeny. In this review we summarize the effects of well-known signaling pathways on several of the most well defined stem cells and argue that the similarity with which unique stem cells from different tissues respond to external stimuli suggests that they share functional mechanisms.