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Journal: Stem cell reviews

172

In a recent study published in this journal it was claimed that the rate of publications from US-based authors in the human embryonic stem cell (hESC) research field was slowing or even declining from 2008 to 2010. It was assumed that this is the result of long-term effects of the Bush administration’s funding policy for hESC research and the uncertain policy environment of recent years. In the present study, we analyzed a pool of more than 1,700 original hESC research papers published world-wide from 2007 to 2011. In contrast to the previous study, our results do not support the hypothesis of a decline in the productivity of US-based research but rather confirm a nearly unchanged leading position of US research in the hESC field with respect to both publication numbers and impact of research. Moreover, we analyzed about 500 papers reporting original research involving human induced pluripotent stem cells (hiPSCs) published through 2011 and found a dominant position of US research in this research field as well.

Concepts: Martin Evans, Pluripotency, Cell biology, Academic publishing, Stem cells, Induced pluripotent stem cell, Embryonic stem cell, Stem cell

28

We researched the survival of bone marrow-derived mesenchymal stem cells (MSCs) and the results of MSCs' injected into decompensated bladders in a rabbit model.

Concepts: Cell biology, Adipocyte, Mesenchyme, Cell division, Stem cells, Bone marrow, Mesenchymal stem cell, Stem cell

28

Evaluation of potential tropic effects of vascular endothelial growth factor (VEGF) on the incorporation and differentiation of bone-marrow-derived stem cells (BMSCs) in a murine model of anterior ischemic optic neuropathy (AION).

Concepts: Stem cell, Developmental biology, Cellular differentiation, Bone marrow, Angiogenesis, Vascular endothelial growth factor, Anterior ischemic optic neuropathy, Ophthalmology

27

Hematopoietic stem cells (HSCs) from umbilical cord blood have been successfully used to treat blood disorders but one major hurdle is the relatively low cell dose available. Double cord blood unit transplantation results in elevated engraftment failure because one unit predominates over the other. Various approaches are thus being undertaken to expand HSCs ex vivo from single cord blood units. We report here a protocol involving slow freezing (-1 °C per minute to -120 °C) + freezing medium containing DMSO + FBS + 24 h-50 % hWJSC-CM that enhances thaw-survival of CD34+ cells. Post-thawing, the fold, percentage and colony forming unit numbers of CD34+ cells were significantly increased (2.08 ± 0.3; 102 ± 1.17 %; 1.07 ± 0.02 respectively) while the percentages of apoptotic, necrotic, dead and sub-G1 phase cells (91.06 ± 3.63 %; 91.80 ± 5.01 %; 95.6 ± 3.61 %; 86.1 ± 16.26 % respectively) were significantly decreased compared to controls. Post-thaw culture in 24 h-50 % hWJSC-CM+FBS for 72 h showed further significant increases in CD34+ cells (fold: 2.28 ± 0.17; percentage: 153.3 ± 21.99 %, CFU: 1.6 ± 0.19) and significant decreases in apoptotic, necrotic, dead and sub-G1 cells (49.2 ± 3.59 %; 62.0 ± 4.30 %; 56.6 ± 5.06 %; 28.6 ± 5.74 % respectively) compared to controls. We hypothesize that these improvements are probably related to the high levels of cytokines, cell adhesion molecules and growth factors in hWJSC-CM that help to preserve cell membrane integrity during freezing and stimulate mitosis post-thaw. A 24 h-50 % hJWSC-CM may be a useful supplement for freezing CD34+ cells in cord blood banks.

Concepts: Stem cells, Cord blood bank, Wharton's jelly, Blood, Bone marrow, Umbilical cord, Stem cell, Cord blood

24

Transparent public discourse about translational stem cell research promotes informed hope about scientific progress and the sustainable development of biotechnologies. Using an a priori coding scheme, we surveyed articles from leading news media about stem cell interventions for neurodegenerative diseases (1991-2014) from United States (n = 83), Canada (n = 29), and United Kingdom (n = 65). While, this analysis of translational contexts in the news demonstrates a lingering tendency to celebrate the benefits of research with little context of its caveats even for chronic neurologic diseases, in a departure from many previous studies, the data also reveal conscientious reporting about stem cell tourism and timeframe estimates for the development of relevant therapeutics.

Concepts: Canada, Science, Developmental biology, United Kingdom, Scientific method, Stem cell, Neurology, Medicine

9

Stem cells continue to garner attention by the news media and play a role in public and policy discussions of emerging technologies. As new media platforms develop, it is important to understand how different news media represents emerging stem cell technologies and the role these play in public discussions. We conducted a comparative analysis of newspaper and sports websites coverage of one recent high profile case: Gordie Howe’s stem cell treatment in Mexico. Using qualitative coding methods, we analyzed news articles and readers' comments from Canadian and US newspapers and sports websites. Results indicate that the efficacy of stem cell treatments is often assumed in news coverage and readers' comments indicate a public with a wide array of beliefs and perspectives on stem cells and their clinical efficacy. Media coverage that presents uncritical perspectives on unproven stem cell therapies may create patient expectations, may have an affect on policy discussions, and help to feed the marketing of unproven therapies. However, news coverage that provides more balanced or critical coverage of unproven stem cell treatments may also inspire more critical discussion, as reflected in readers' comments.

Concepts: Journalism, Psychology, Cell biology, Mass media, Cell division, Stem cells, Stem cell treatments, Stem cell

4

Human peripheral blood and umbilical cord blood represent attractive sources of cells for reprogramming to induced pluripotent stem cells (iPSCs). However, to date, most of the blood-derived iPSCs were generated using either integrating methods or starting from T-lymphocytes that have genomic rearrangements thus bearing uncertain consequences when using iPSC-derived lineages for disease modeling and cell therapies. Recently, both peripheral blood and cord blood cells have been reprogrammed into transgene-free iPSC using the Sendai viral vector. Here we demonstrate that peripheral blood can be utilized for medium-throughput iPSC production without the need to maintain cell culture prior to reprogramming induction. Cell reprogramming can also be accomplished with as little as 3000 previously cryopreserved cord blood cells under feeder-free and chemically defined Xeno-free conditions that are compliant with standard Good Manufacturing Practice (GMP) regulations. The first iPSC colonies appear 2-3 weeks faster in comparison to previous reports. Notably, these peripheral blood- and cord blood-derived iPSCs are free of detectable immunoglobulin heavy chain (IGH) and T cell receptor (TCR) gene rearrangements, suggesting they did not originate from B- or T- lymphoid cells. The iPSCs are pluripotent as evaluated by the scorecard assay and in vitro multi lineage functional cell differentiation. Our data show that small volumes of cryopreserved peripheral blood or cord blood cells can be reprogrammed efficiently at a convenient, cost effective and scalable way. In summary, our method expands the reprogramming potential of limited or archived samples either stored at blood banks or obtained from pediatric populations that cannot easily provide large quantities of peripheral blood or a skin biopsy.

Concepts: Protein, Stem cells, Developmental biology, Blood, Cord blood, DNA, Cell biology, Stem cell

3

The practice of travelling abroad to receive unproven and unregulated stem cell treatments has become an increasingly problematic global phenomenon known as ‘stem cell tourism’. In this paper, we examine representations of nine major clinics and providers of such treatments on the microblogging network Twitter. We collected and conducted a content analysis of Twitter posts (n = 363) by these establishments and by other users mentioning them, focusing specifically on marketing claims about treatment procedures and outcomes, discussions of safety and efficacy of stem cell transplants, and specific representations of patients' experiences. Our analysis has shown that there were explicit claims or suggestions of benefits associated with unproven stem cell treatments in approximately one third of the tweets and that patients' experiences, whenever referenced, were presented as invariably positive and as testimonials about the efficacy of stem cell transplants. Furthermore, the results indicated that the tone of most tweets (60.2 %) was overwhelmingly positive and there were rarely critical discussions about significant health risks associated with unproven stem cell therapies. When placed in the context of past research on the problems associated with the marketing of unproven stem cell therapies, this analysis of representations on Twitter suggests that discussions in social media have also remained largely uncritical of the stem cell tourism phenomenon, with inaccurate representations of risks and benefits for patients.

Concepts: Hospital, Organ transplant, Microblogging, Stem cell treatments, Marketing, Stem cell, Twitter

2

We have recently described manufacturing of human induced pluripotent stem cells (iPSC) master cell banks (MCB) generated by a clinically compliant process using cord blood as a starting material (Baghbaderani et al. in Stem Cell Reports, 5(4), 647-659, 2015). In this manuscript, we describe the detailed characterization of the two iPSC clones generated using this process, including whole genome sequencing (WGS), microarray, and comparative genomic hybridization (aCGH) single nucleotide polymorphism (SNP) analysis. We compare their profiles with a proposed calibration material and with a reporter subclone and lines made by a similar process from different donors. We believe that iPSCs are likely to be used to make multiple clinical products. We further believe that the lines used as input material will be used at different sites and, given their immortal status, will be used for many years or even decades. Therefore, it will be important to develop assays to monitor the state of the cells and their drift in culture. We suggest that a detailed characterization of the initial status of the cells, a comparison with some calibration material and the development of reporter sublcones will help determine which set of tests will be most useful in monitoring the cells and establishing criteria for discarding a line.

Concepts: Pluripotency, Bioinformatics, Developmental biology, Cell biology, Stem cells, Induced pluripotent stem cell, DNA, Stem cell

2

Neuronal degeneration within the substantia nigra and the loss of the dopaminergic nigro-striatal pathway are the major hallmarks of Parkinson’s disease (PD). Grafts of foetal ventral mesencephalic (VM) dopaminergic (DA) neurons into the striatum have been shown to be able to restore striatal dopamine levels and to improve overall PD symptoms. However, human foetus-derived cell grafts are not feasible for clinical application. Autologous induced pluripotent stem cell (iPS cell)-derived DA neurons are emerging as an unprecedented alternative. In this review, we summarize and compare the efficacy of human iPS cell-derived DA neuron grafts to restore normal behaviour in a rat model for PD with that of human foetal primary DA neurons. The differences we observed in the efficacy to restore normal function between the 2 types of DA neuron grafts could be ascribed to intrinsic properties of the iPS cell-derived DA neurons that critically affected survival and proper neurite extension in the striatum after implantation.

Concepts: Basal ganglia, Neuron, Striatum, Neurotransmitter, Parkinson's disease, Substantia nigra, Stem cell, Dopamine