bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a simple procedure for the treatment of femoral head osteonecrosis with intra-osseous injection of bone marrow mesenchymal stromal cells: study of their biodistribution in the early time points after injection
Authors: Lebouvier Angélique , Poignard Alexandre , Cavet Madeleine , Amiaud Jérôme , Leotot Julie , Hernigou Philippe , Rahmouni Alain , Bierling Philippe , Layrolle Pierre , Rouard Hélène , Chevallier Nathalie 
Published: April 2015

Abstract
Introduction
Osteonecrosis of the femoral head (ONFH) is a degenerative disease progressing to a femoral head (FH) collapse. Injection of osteoprogenitor cells like bone marrow mesenchymal stromal cells (BMSCs) into the FH appears to be a good therapeutic treatment. However, safety and efficacy of BMSCs to treat bone defect are the main preclinical data required for clinical application. Efficacy and the lack of risk of cell transformation after amplification of BMSCs have been extensively described. The main objectives of this study were to develop a simple and usable procedure for clinicians and control its feasibility by evaluating the biodistribution of BMSCs after injection into the FH in a large animal model. The impact of this approach was evaluated on one natural pig ONFH.

Methods
BMSCs were directly injected in the pig FH, and then the biodistribution of grafted cells was detected by quantitative real-time polymerase chain reaction, cytometry, or a combination of classic histology analysis and in situ hybridization (ISH). BMSC efficacy on bone regeneration was evaluated by magnetic resonance imaging (MRI) and histology.

Results
After 30-minute and 24-hour follow-up, grafted cells were detected at the injection site and no BMSCs were detected in filter organs or body fluids. The combination of classic histology analysis and ISH showed a good homogeneity of cell distribution in FH. Local delivery of BMSCs onto a bone scaffold associated with bone formation in vivo confirmed the preferential tropism of BMSCs to the bone tissue as well as their efficacy to form bone. Treatment of a natural pig ONFH by autologous BMSCs indicated a beginning of bone healing as early as 2 weeks with a complete healing after 9 weeks. At this stage, MRI and histological analysis were similar to those of a normal FH.

Conclusions
Intra-osseous injection of BMSCs in FH seems to be a good strategy for ONFH treatment as the safety concerning the biodistribution of BMSCs is ensured. Moreover, the efficacy of BMSCs in natural ONFH seems to indicate that this is a promising approach. Altogether, these results constitute the preclinical data necessary for the setup of a clinical application with expanded BMSCs in the context of advanced therapy medicinal products.
Microencapsulated equine mesenchymal stromal cells promote cutaneous wound healing in vitro
Authors: Bussche Leen , Harman Rebecca M , Syracuse Bethany A , Plante Eric L , Lu Yen-Chun , Curtis Theresa M , Ma Minglin , Van de Walle Gerlinde R 
Published: April 2015

Abstract
Introduction
The prevalence of impaired cutaneous wound healing is high and treatment is difficult and often ineffective, leading to negative social and economic impacts for our society. Innovative treatments to improve cutaneous wound healing by promoting complete tissue regeneration are therefore urgently needed. Mesenchymal stromal cells (MSCs) have been reported to provide paracrine signals that promote wound healing, but (i) how they exert their effects on target cells is unclear and (ii) a suitable delivery system to supply these MSC-derived secreted factors in a controlled and safe way is unavailable. The present study was designed to provide answers to these questions by using the horse as a translational model. Specifically, we aimed to (i) evaluate the in vitro effects of equine MSC-derived conditioned medium (CM), containing all factors secreted by MSCs, on equine dermal fibroblasts, a cell type critical for successful wound healing, and (ii) explore the potential of microencapsulated equine MSCs to deliver CM to wounded cells in vitro.

Methods
MSCs were isolated from the peripheral blood of healthy horses. Equine dermal fibroblasts from the NBL-6 (horse dermal fibroblast cell) line were wounded in vitro, and cell migration and expression levels of genes involved in wound healing were evaluated after treatment with MSC-CM or NBL-6-CM. These assays were repeated by using the CM collected from MSCs encapsulated in core-shell hydrogel microcapsules.

Results
Our salient findings were that equine MSC-derived CM stimulated the migration of equine dermal fibroblasts and increased their expression level of genes that positively contribute to wound healing. In addition, we found that equine MSCs packaged in core-shell hydrogel microcapsules had similar effects on equine dermal fibroblast migration and gene expression, indicating that microencapsulation of MSCs does not interfere with the release of bioactive factors.

Conclusions
Our results demonstrate that the use of CM from MSCs might be a promising new therapy for impaired cutaneous wounds and that encapsulation may be a suitable way to effectively deliver CM to wounded cells in vivo.
Altered protein secretions during interactions between adipose tissue- or bone marrow-derived stromal cells and inflammatory cells
Authors: Hattori Hidemi , Ishihara Masayuki 
Published: April 2015

Abstract
Introduction
Paracrine effects can be exploited in cell-based therapies that secrete factors, such as chemokines and cytokines, and can recruit inflammatory cells to transplants. In this study, mouse adipose tissue-derived stromal cells (ASCs) and bone marrow-derived stromal cells (ST2 cells) were used to examine changes in paracrine interactions with inflammation cells.

Methods
Green fluorescent protein positive (GFP+) bone marrow cells (BMCs) were injected into an irradiated mouse via the femoral vein, and ASCs and ST2 cells were transplanted intradermally. Subsequently, an in vivo imaging system was used to observe behaviors of GFP+ BMCs. To detect bone marrow-derived inflammatory cells which migrated to the ASC and ST2 cell transplantation area, the sections were immunostained using antibodies against Gr1, CD11c, and F4/80, and secretory proteins were detected in culture medium using enzyme-linked immunosorbent assay.

Results
Many bone marrow-derived inflammatory cells migrated to ASC and ST2 cell transplantation sites. Among these, neutrophils were detected during the early period and macrophages were predominantly detected at a later point in time. Many chemokines, cytokines, growth factors, matrix metalloproteinases (MMPs), and tissue inhibitors of metalloproteinases (TIMPs) were secreted in abundance from ASCs, and the secretion increased by co-culturing with inflammatory cells, except for secretions of insulin-like growth factor-1, MMP-9 and MMP-13. Although secretions from ST2 cells were less than those from ASCs, co-culture with inflammatory cells increased these secretions to levels similar to those of ASCs. However, unlike ASCs, the ST2 cells did not secrete angiostatin, MMP-2, or MMP-3. Finally, ASCs secreted not only proinflammatory cytokines, angiogenic factors and MMPs but also anti-inflammatory cytokines, anti-angiogenesis factors, and TIMPs.

Conclusions
The effects of cell-based therapies using ASCs and ST2 cells are depended on paracrine effects that are mediated by chemokines, cytokines, growth factors, MMPs, and TIMPs, which comprise responses to interactions between transplanted cells and inflammatory cells. Moreover, paracrine effects of transplanted cells are influenced by inflammatory cells, and are moderated by a balance of secreted inhibitors.
Ascorbic acid improves pluripotency of human parthenogenetic embryonic stem cells through modifying imprinted gene expression in the Dlk1-Dio3 region
Authors: Yu Yang , Gao Qian , Zhao Hong-cui , Li Rong , Gao Jiang-man , Ding Ting , Bao Si-yu , Zhao Yue , Sun Xiao-fang , Fan Yong , Qiao Jie 
Published: April 2015

Abstract
Introduction
Human parthenogenetic embryonic stem cells (hpESCs) are generated from artificially activated oocytes, however, the issue of whether hpESCs have equivalent differentiation ability to human fertilized embryonic stem cells remains controversial.

Methods
hpESCs were injected into male severe combined immunodeficiency (SCID) mice and the efficiency of teratoma formation was calculated. Then the gene expression and methylation modification were detected by real time-PCR and bisulfate methods.

Results
Comparison of five hpESCs with different differentiation abilities revealed that levels of paternal genes in the Dlk1-Dio3 region on chromosome 14 in the hpESCs with high differentiation potential are enhanced, but strictly methylated and silenced in the hpESCs with lower differentiation potential. Treatment with ascorbic acid, rescued their ability to support teratoma formation and altered the expression profiles of paternally expressed genes in hpESCs that could not form teratoma easily. No differences in the expression of other imprinting genes were evident between hpESCs with higher and lower differentiation potential, except for those in the Dlk1-Dio3 region.

Conclusions
The Dlk1-Dio3 imprinting gene cluster distinguishes the differentiation ability of hpESCs. Moreover, modification by ascorbic acid may facilitate application of hpESCs to clinical settings in the future by enhancing their pluripotency.
Ex vivo exposure of bone marrow from chronic kidney disease donor rats to pravastatin limits renal damage in recipient rats with chronic kidney disease
Authors: van Koppen Arianne , Papazova Diana A , Oosterhuis Nynke R , Gremmels Hendrik , Giles Rachel H , Fledderus Joost O , Joles Jaap A , Verhaar Marianne C 
Published: April 2015

Abstract
Introduction
Healthy bone marrow cell (BMC) infusion improves renal function and limits renal injury in a model of chronic kidney disease (CKD) in rats. However, BMCs derived from rats with CKD fail to retain beneficial effects, demonstrating limited therapeutic efficacy. Statins have been reported to improve cellular repair mechanisms.

Methods
We studied whether exposing CKD rat BMCs ex vivo to pravastatin improved their in vivo therapeutic efficacy in CKD and compared this to systemic in vivo treatment. Six weeks after CKD induction, healthy BMCs, healthy pravastatin-pretreated BMCs, CKD BMCs or CKD pravastatin-pretreated BMCs were injected into the renal artery of CKD rats.

Results
At 6 weeks after BMC injection renal injury was reduced in pravastatin-pretreated CKD BMC recipients vs. CKD BMC recipients. Effective renal plasma flow was lower and filtration fraction was higher in CKD BMC recipients compared to all groups whereas there was no difference between pravastatin-pretreated CKD BMC and healthy BMC recipients. Mean arterial pressure was higher in CKD BMC recipients compared to all other groups. In contrast, 6 weeks of systemic in vivo pravastatin treatment had no effect. In vitro results showed improved migration, decreased apoptosis and lower excretion of pro-inflammatory Chemokine (C-X-C Motif) Ligand 5 in pravastatin-pretreated CKD BMCs.

Conclusions
Short ex vivo exposure of CKD BMC to pravastatin improves CKD BMC function and their subsequent therapeutic efficacy in a CKD setting, whereas systemic statin treatment did not provide renal protection.
Comparative analysis of human mesenchymal stem cells from bone marrow and adipose tissue under xeno-free conditions for cell therapy
Authors: Li Chun-yu , Wu Xiao-yun , Tong Jia-bei , Yang Xin-xin , Zhao Jing-li , Zheng Quan-fu , Zhao Guo-bin , Ma Zhi-jie 
Published: April 2015

Abstract
Introduction
Mesenchymal stem cells (MSCs) are promising candidates for cell-based therapies. Human platelet lysate represents an efficient alternative to fetal bovine serum for clinical-scale expansion of MSCs. Different media used in culture processes should maintain the biological characteristics of MSCs during multiple passages. However, bone marrow-derived MSCs and adipose tissue-derived MSCs have not yet been directly compared with each other under human platelet lysate conditions. This study aims to conduct a direct head-to-head comparison of the biological characteristics of the two types of MSCs under human platelet lysate-supplemented culture conditions for their ability to be used in regenerative medicine applications.

Methods
The bone marrow- and adipose tissue-derived MSCs were cultured under human platelet lysate conditions and their biological characteristics evaluated for cell therapy (morphology, immunophenotype, colony-forming unit-fibroblast efficiency, proliferation capacity, potential for mesodermal differentiation, secreted proteins, and immunomodulatory effects).

Results
Under human platelet lysate-supplemented culture conditions, bone marrow- and adipose tissue-derived MSCs exhibited similar fibroblast-like morphology and expression patterns of surface markers. Adipose tissue-derived MSCs had greater proliferative potential than bone marrow-derived MSCs, while no significantly difference in colony efficiency were observed between the two types of cells. However, bone marrow-derived MSCs possessed higher capacity toward osteogenic and chondrogenic differentiation compared with adipose tissue-derived MSCs, while similar adipogenic differentiation potential wase observed between the two types of cells. There were some differences between bone marrow- and adipose tissue-derived MSCs for several secreted proteins, such as cytokine (interferon-γ), growth factors (basic fibroblast growth factor, hepatocyte growth factor, and insulin-like growth factor-1), and chemokine (stem cell-derived factor-1). Adipose tissue-derived MSCs had more potent immunomodulatory effects than bone marrow-derived MSCs.

Conclusions
Adipose tissue-derived MSCs have biological advantages in the proliferative capacity, secreted proteins (basic fibroblast growth factor, interferon-γ, and insulin-like growth factor-1), and immunomodulatory effects, but bone marrow-derived MSCs have advantages in osteogenic and chondrogenic differentiation potential and secreted proteins (stem cell-derived factor-1 and hepatocyte growth factor); these biological advantages should be considered systematically when choosing the MSC source for specific clinical application.
Adipose tissue-derived stem cell therapy in rat cryopreserved ovarian grafts
Authors: Damous Luciana Lamarão , Nakamuta Juliana Sanajotti , de Carvalho Ana Elisa Teófilo Saturi , Soares-Jr José Maria , de Jesus Simões Manuel , Krieger José Eduardo , Baracat Edmund C 
Published: April 2015

AbstractThe preliminary results of ovarian transplantation in clinical practice are encouraging. However, the follicular depletion caused by ischemic injury is a main concern and is directly related to short-term graft survival. Cell therapy with adipose tissue-derived stem cells (ASCs) could be an alternative to induce early angiogenesis in the graft. This study aimed to evaluate ASCs therapy in rat cryopreserved ovarian grafts. A single dose of rat ASC (rASCs) or vehicle was injected into the bilateral cryopreserved ovaries of twelve adult female rats immediately after an autologous transplant. Daily vaginal smears were performed for estrous cycle evaluation until euthanasia on postoperative day 30. Follicle viability, graft morphology and apoptosis were assessed. No differences were found with respect to estrous cycle resumption and follicle viability (P > 0.05). However, compared with the vehicle-treated grafts, the morphology of the ASCs-treated grafts was impaired, with diffuse atrophy and increased apoptosis (P < 0.05). ASCs direct injected in the stroma of rat cryopreserved ovarian grafts impaired its morphology although may not interfere with the functional resumption on short-term. Further investigations are necessary to evaluated whether it could compromise their viability in the long-term.
Design and conduct of Xtreme Everest 2: An observational cohort study of Sherpa and lowlander responses to graduated hypobaric hypoxia
Authors: Gilbert-Kawai Edward , Sheperdigian Adam , Adams Thomas , Mitchell Kay , Feelisch Martin , Murray Andrew , Peters Mark , Gilbert-Kawai Grace , Montgomery Hugh , Levett Denny , Kumar Rajendra , Mythen Michael , Grocott Michael , Martin Daniel 
Published: April 2015

Objective: Oxygen availability falls with ascent to altitude and also as a consequence of critical illness. Because cellular sequelae and adaptive processes may be shared in both circumstances, high altitude exposure (‘physiological hypoxia’) assists in the exploration of the response to pathological hypoxia. We therefore studied the response of healthy participants to progressive hypobaric hypoxia at altitude. The primary objective of the study was to identify differences between high altitude inhabitants (Sherpas) and lowland comparators.Methods: We performed an observational cohort study of human responses to progressive hypobaric hypoxia (during ascent) and subsequent normoxia (following descent) comparing Sherpas with lowlanders. Studies were conducted in London (35m), Kathmandu (1300m), Namche Bazaar (3500m) and Everest Base Camp (5300m). Of 180 healthy volunteers departing from Kathmandu, 64 were Sherpas and 116 were lowlanders. Physiological, biochemical, genetic and epigenetic data were collected. Core studies focused on nitric oxide metabolism, microcirculatory blood flow and exercise performance. Additional studies performed in nested subgroups examined mitochondrial and metabolic function, and ventilatory and cardiac variables. Of the 180 healthy participants who left Kathmandu, 178 (99%) completed the planned trek. Overall, more than 90% of planned testing was completed. Forty-four study protocols were successfully completed at altitudes up to and including 5300m. A subgroup of identical twins (all lowlanders) was also studied in detail.Conclusion: This programme of study (Xtreme Everest 2) will provide a rich dataset relating to human adaptation to hypoxia, and the responses seen on re-exposure to normoxia. It is the largest comprehensive high altitude study of Sherpas yet performed. Translational data generated from this study will be of relevance to diseases in which oxygenation is a major factor.
Reviews
Authors: Southwood Russell , Miller Toby , Evens Tom 
Published: April 2015

Abstract
Broadband as a Video Platform – Strategies for Africa, Judith O’Neill, Eli M. Noam and Darcy Gerbarg (eds) (2014) Springer: Berlin, 177 pp. ISBN: 9783319036168, h/bk, ¢æ84
Data Journalism: Mapping the Future, John Mair, Richard Lance Keeble, Paul Bradshaw and Teodora Beleaga (eds) (2013) Abramis: Bury St Edmunds, 187 pp. ISBN: 9781845496166, p/bk, $23.85
Screen Distribution and the New King Kongs of the Online World, Stuart Cunningham and Jon Silver (2013) Basingstoke: Palgrave Macmillan, 132 pp. ISBN: 9781137326447, h/bk, £47
Allelic Imbalance Is a Prevalent and Tissue-Specific Feature of the Mouse Transcriptome
Authors: Pinter Stefan F , Colognori David , Beliveau Brian J , Sadreyev Ruslan I , Payer Bernhard , Yildirim Eda , Wu Chao-ting , Lee Jeannie T 
Published: April 2015

AbstractIn mammals, several classes of monoallelic genes have been identified, including those subject to X-chromosome inactivation (XCI), genomic imprinting, and random monoallelic expression (RMAE). However, the extent to which these epigenetic phenomena are influenced by underlying genetic variation is unknown. Here we perform a systematic classification of allelic imbalance in mouse hybrids derived from reciprocal crosses of divergent strains. We observe that deviation from balanced biallelic expression is common, occurring in ∼20% of the mouse transcriptome in a given tissue. Allelic imbalance attributed to genotypic variation is by far the most prevalent class and typically is tissue-specific. However, some genotype-based imbalance is maintained across tissues and is associated with greater genetic variation, especially in 5′ and 3′ termini of transcripts. We further identify novel random monoallelic and imprinted genes and find that genotype can modify penetrance of parental origin even in the setting of large imprinted regions. Examination of nascent transcripts in single cells from inbred parental strains reveals that genes showing genotype-based imbalance in hybrids can also exhibit monoallelic expression in isogenic backgrounds. This surprising observation may suggest a competition between alleles and/or reflect the combined impact of cis- and trans-acting variation on expression of a given gene. Our findings provide novel insights into gene regulation and may be relevant to human genetic variation and disease.
PROFIL PROFESIONALISME GURU MADRASAH IBTIDAIYAH UNGGULAN DI JAKARTA SELATAN
Authors: Asy'ari Hasyim , Latip Asep Ediana 
Published: April 2015

Abstract : This study aims at formulating a model of the profile of teachers professionalism of excellent Islamic Primary School (IPS). The source of data of this research is obtained from six excelence IPS in South Jakarta that achieve score of accreditation A.This research is a non experimental research that uses survey method. The population of this research is all teachers in 15 Excelence IPS with the sample as much as 40% of the teachers. as many as 100 teachers. As for the sampling technique used in this research is simple random sampling with descriptive statistics. The result of this research shows that firstly the profile of professionalism of the teachers of excellent IPS in South Jakarta is indicated by adequate teachers competency in personality, pedagogy, professionalism, and social aspect. Secondly, at the dimension of learning community teachers have not fully showed self development as a part of learning community. Thirdly, at the financial dimension it is know that the teachers of especially State Islamic Primary Schools are willing to accept all the policy of reward system set by the goverment and their schools headmasters. Fourtly, the linearity of educational background with the teaching profession. Fifthly, there is no difference in average scores the characteristics of profile of teachers professionalism between Private Islamic Primary Schools and the State ones. DOI: 10.15408/tjems.v1i1.1110
Synthesis of Nanocarbons Using a Large Volume AC Plasma Reactor
Authors: Hamady M. , Sheppard D. , Seddighi K. , Sarawagi A. , Scott B. , Wilcox K. , Gerber A. , Chibante L.P.F. 
Published: April 2015

ABSTRACTThere is an opportunity for scaling up, optimizing, and controlling the process of production of nanoparticles due to their numerous diverse applications. We present a system for continuous, high rate production of nanoparticles, particularly those of carbon, using large volume thermal plasma based on a three-phase diverging electrode configuration. The goal of using this 3-phase plasma reactor is to have a plasma arc that is scalable, self-stabilizing, and low maintenance, with sufficient plasma volume to maximize residence time of feed materials for evaporation to atomic species. Plasma carrier gas, typically inert gas such as helium, is injected into the reactor allowing the vaporization of any feedstock due to plasma temperatures >5000 °C. Controlling plasma enthalpy, diffusion/temperature gradients and carbon feed rates allow the controlled growth of clusters leading to nanoparticles less than 100 nm. Once the desired size is achieved the gas stream is expanded to reduce the reaction rate and quenched by natural cooling to chamber walls or injection of a cooling gas stream, preferably of the same composition as plasma carrier gas. Recoverable yields in the nanoparticle-laden gas stream are then isolated by standard means (filtration, cyclone separation, electrostatic precipitation), and the plasma gas and unreacted feedstock are routed to the plasma reactor for recycling. Computational Fluid Dynamics (CFD) is employed to measure and predict fluid flow, energy/temperature, and other species distributions in the plasma process.