Embryonic Stem Cell Research Research Articles

Evaluation of patients with multiple sclerosis using reverse nutech functional score and expanded disability status scale after human embryonic stem cell therapy.

BackgroundThe expanded disability status scale (EDSS) is a validated and reliable tool to assess the extent of disabilities in patients with multiple sclerosis (MS). However, the use of this tool has been found to be limited in assessing various symptoms of MS that are important. Our study aimed at evaluating the efficacy of a new scoring system, reverse nutech functional score (RNFS) as compared to EDSS in assessing patients with MS treated with human embryonic stem cell (hESC) therapy.MethodsThe MS patients were treated with hESC therapy for one treatment period. All the patients were evaluated with EDSS and RNFS at baseline and after the hESC therapy.ResultsThe study included a total of 24 MS patients with mean age of 45 year. The patients showed an improvement in parameters (sleeping disorders, paralysis, paraesthesia, myalgia, muscle weakness, memory, language, irritability, eye pain, depression and coordination, communication, breathing pattern, attention and appetite) associated with MS when evaluated with RNFS. This improvement went unnoticed when the patients were assessed with EDSS.ConclusionRNFS can efficiently assess the effectiveness of hESC therapy in treating patients with MS. It could be a suitable scoring system for patients with MS as it can assess the slightest improvements in the patients. Use in other settings would be helpful in assessing its utility.

Embryonic Stem Cell Research: A Policy Analysis.

Many health care issues generate minimal passion, promoting benign commentary and support from the various stakeholders involved. Stem cell research does not fall into this category, and on the contrary, embryonic stem cell (ESC) research has continued to foster controversy and emotion. Since 1998, which marked the first successful laboratory isolation of ESCs, this research continues to ignite moral, ethical, and legal debate over its efficacy. The focus of this policy analysis is to introduce the issues, examine and address the various perspectives that surround ESC research, and present policy options and/or solutions that may be used to successfully create a policy consensus regarding this much debated topic.

Embryonic Stem Cell Research: A Policy Analysis.

Embryonic Stem Cell Research: A Policy Analysis.

Discursive Contextures of Science: Euro/West-Centrism and Science and Technology Studies

Science and Technology Studies (STS) by the very act of showing the multiplicity, contingency, and context-dependence of scientific knowledge and practice, provincialized modern science. Postcolonial interventions within STS have pursued this goal even further. Nevertheless, Euro/West-centrism continues to inflect not only scientific practices and lay imaginaries, but also sociological and historical analyses of sciences. In this article, drawing on my own training within STS – first under J.P.S. Uberoi, who was concerned with structuralist analysis of modernity and science, and thereafter under Andy Pickering, when we focused on material agency and temporal emergence and extensively engaged with Actor Network Theory - I emphasize the continuing role of Euro/West-centric discourses in defining the “self” and the “other” and in impacting epistemological and ontological interventions. More broadly, building on a concept of Michael Lynch’s, I call for excavation and analysis of discursive contextures of sciences. In the second section of the article, through a brief analysis of embryonic stem cell therapy in a clinic in Delhi, I show how with shifting transnational landscape of technoscience certain discursive contextures are being “deterritorialized” and left “stuttering.”

Ethical Assessment of Human Embryonic Stem Cell Research According to Turkish Muslim Scholars: First Critical Analysis and Some Reflections

Turkey, with a Muslim population of officially over 99%, is one of the few secular states in the Muslim world. Although state institutions are not based on Islamic juridical and ethical norms, the latter play a significant role in defining people's attitudes towards controversial issues in the modern world, especially when backed by opinions of Muslim scholars living in Turkey. Accordingly, opinions of Muslim scholars undoubtedly have an important effect on bioethical decisions made by institutions and individuals. To explore the ethical positions of Muslim scholars living in Turkey and their arguments used in the ethical assessment of embryonic stem cell research; to discuss the biological-moral tensions arising in medical research on human embryos. Qualitative study. Muslim scholars located in different parts of Turkey. Qualitative method, involving the collection of opinions of various scholars, by means of 15 individual semi-structured interviews, evaluated using thematic qualitative analysis. Positions regarding embryonic stem cell research differ among Muslim scholars in Turkey. On the other hand, even where positions are similar, they are often supported by different arguments. Despite the heterogeneity of the arguments presented, the dominant position considers embryonic stem cell research as morally acceptable.

Human Embryonic Stem Cell Therapy in Chronic Spinal Cord Injury: A Retrospective Study.

Human embryonic stem cells (hESCs) have a role in treating neurological disorders. The efficacy and safety of hESC in treating spinal cord injury (SCI) was reported in our previous study. In the present study, we have evaluated the efficacy and safety of hESC therapy in 226 patients with SCI. In the first treatment phase (T1), 0.25 mL hESCs were administered intramuscularly twice daily, 1 mL every 10 days i.v., and 1–5 mL every 7 days. Of 153 patients in the American Spinal Injury Association (ASIA) scale A at the beginning of T1, a significant number of patients (n = 80; 52.3%) moved to lower scales at the end of T1 (p = 0.01). At the end of T2, of 32 patients in ASIA scale A, 12 patients (37.5%) moved to scale B (p = 0.01). Of 19 patients, 3 patients (37.5%) moved to scale B at the end of T3 (p = 0.02). No serious adverse events (AEs) were observed. hESC transplantation is safe and effective.

Derivation of motor neuron-like cells from neonatal mouse testis in a simple culture condition.

Embryonic stem cell (ESC) therapy is an exciting way to treat neurodegenerative disease and central nervous system injury. However, many ethical and immunological problems surround the use of embryonic stem cells. Finding an alternative source of stem cells is therefore pertinent. In this study, spermatogonia stem cells (SSCs) were used to generate mature motor neurons. SSCs were extracted from neonatal testes and cultured in DMED/F12 medium for 3weeks. Characterisation of SSC-derived ESC-like cells was confirmed by RT-qPCR, immunostaining, alkaline phosphatase activity and their ability to form embryoid bodies (EBs). The EBs were induced by retinoic acid and Sonic hedgehog and trypsinised to obtain single induced cells. The single cells were cultured in neural medium for 18days. Characterisation of neural precursors and motor neuron-like cells was confirmed by RT-qPCR and immunocytochemical analysis at the 7th day (early stage) and 18th day (late stage), respectively, of culturing. The neural precursors were found to be positive for nestin and Sox2, and a small fraction of cells expressed β-tubulin III. Upon further differentiation, multipolar neurons were detected that expressed β-tubulin III and MAP2 markers. Moreover, the expression levels of Olig2 and PAX6 were significantly lower, while HB9, Isl1 and Isl2 expression levels were higher at the late stage when compared to the early stage. These results show that SSCs have the potential to differentiate to motor neuron-like cells and express markers specific for mature motor neurons. However, the functional ability of these cells remains to be evaluated in future studies.

Modelling the in-utero initation of ETV6-RUNX1 in childhood acute lymphoblastic leukaemia using human pluripotent stem cells

BackgroundWe hypothesise that the clinical differences between adult and childhood acute lymphoblastic leukaemia (cALL) arise partly through their origin in developmentally distinct target cells. Since cALL frequently initiates in utero we aimed to characterise the earliest stages of lymphoid development in human fetal liver. In parallel we used human pluripotent stem cells (hPSC) to recapitulate fetal liver lymphopoiesis and model the impact of the fusion oncogene ETV6-RUNX1, the commonest genetic aberration in cALL. MethodsH1 human embyronic stem cells and MIFF3 human induced hPSCs (provided by University of Sheffield Centre for Stem Cell Biology) were maintained in vitro with mTeSR1/Matrigel. Vectors were produced by recombineering an ETV6 bacterial artificial chromosome with a custom DNA cassette (GeneArt, ThermoFisher, Waltham MA, USA). Vectors were transfected (Nucleofector II, Lonza, Basle, Switzerland) and G418-selected clones were screened by Southern blot. hPSCs were differentiated by sequential OP9/MS5 coculture. Populations sorted by fluorescence-activated cell sorting were analysed by single cell real-time PCR (Biomark 48.48, Fluidigm, San Fransisco, CA, USA) and 200 cell RNA sequencing. Human fetal livers were donated under informed consent with approval of Lund University Ethical Review Board and the Swedish National Board of Health and Welfare. FindingsB lymphopoiesis in the fetal liver was distinct from that in adult bone marrow or neonatal cord blood: the earliest fetal liver B cells did not fully express mature lymphoid effectors and the earliest identified lymphoid-capable progenitors coexpressed both lymphoid and myeloid gene expression programmes. Global and single cell gene expression profiling of B lymphopoietic progenitors generated by in vitro differentiation of hPSCs showed that they share the same transcriptional programme. hPSCs that were CRISPR-engineered to express ETV6-RUNX1 were partly arrested in B cell differentiation at the level of the lymphomyeloid progenitor. B cells that passed this block shared the global gene expression signature of the fetal lymphomyeloid progenitor, and single cell real-time PCR showed that they aberrantly coexpressed B and myeloid lineage genes. InterpretationOur results identify a B lymphoid progenitor in human fetal liver characterised by coexpression of lymphoid and myeloid gene expression programmes and suggest that this progenitor's B myeloid signature provides a permissive transcriptional context for ETV6-RUNX1 to effect a partial differentiation arrest. The developmental specificity of the gene expression signature of this cell could offer unique therapeutic targets, and the hSPC model might provide a novel drug-screening platform. FundingWellcome Trust Research Training Fellowship and NIHR Academic Clinical Fellowship (SR); Swedish Childhood Cancer Foundation (CB); Bloodwise, Cancer Research UK, Children with Cancer, and Great Ormond Street Hospital Children's Charity (TE).

High throughput screen: stress forced differentiation and potency loss of embyronic stem cells

High throughput screen: stress forced differentiation and potency loss of embyronic stem cells

The Italian Way to Stem Cell Research: Rethinking the Role of Catholic Religion in Shaping Italian Stem Cell Research Regulations.

Stem cell research regulations are highly variable across nations, notwithstanding shared and common ethical concerns. Dominant in political debates has been the so-called embryo question. However, the permissibility of human embryonic stem cell (hESC) research varies among national regulatory frameworks. Scholars have explained differences by resorting to notions of political culture, traditions of ethical reasoning, discursive strategies and political manoeuvring of involved actors. Explanations based on the role of religion or other cultural structural variables are also employed. This paper analyses the emerging of the Italian regulatory framework on stem cell research using an analytical framework that considers the interplay between cultural structural features, political culture, traditions of ethical reasoning, institutional settings and the discursive and political agency of the actors involved. It aims also to explain the role of Roman Catholic Church in shaping the Italian stem cell research regulation not by treating religion as an autonomous causal factor, but through the analysis of the agency of Catholic and allied actors in the Italian political culture and institutional setting.

Induced pluripotent stem cells: methods, disease modeling, and microenvironment for drug discovery and screening

The raging ethical, religious, moral, political, and safety issues pertaining to the use of embryonic stem cells for therapy and research have prompted researchers to develop possibly better alternatives that are more efficacious and serve multiple purposes. Induced pluripotent stem cells (iPSCs) developed by multiple methods provide an unparalleled source of cells that could be differentiated into progeny cells. In cell-based disease models the progeny cells mimic, at least in part, the pathology of the studied disease and are used to improve the mechanistic understanding of the pathology. Furthermore, these cells could be used to test the efficacy and safety of drugs that can reverse this phenotype. This review provides an overview of the aforesaid methods for iPSC generation and the development of certain disease-based model systems. In this review, the focus is on model systems for neurological and hematological diseases. Last but not least, the importance of the microenvironment is underscored and the significance of these model systems is discussed in the context of drug screening and development.

Induced Pluripotent Stem Cells: Generation Strategy and Epigenetic Mystery behind Reprogramming.

Possessing the ability of self-renewal with immortalization and potential for differentiation into different cell types, stem cells, particularly embryonic stem cells (ESC), have attracted significant attention since their discovery. As ESC research has played an essential role in developing our understanding of the mechanisms underlying reproduction, development, and cell (de)differentiation, significant efforts have been made in the biomedical study of ESC in recent decades. However, such studies of ESC have been hampered by the ethical issues and technological challenges surrounding them, therefore dramatically inhibiting the potential applications of ESC in basic biomedical studies and clinical medicine. Induced pluripotent stem cells (iPSCs), generated from the reprogrammed somatic cells, share similar characteristics including but not limited to the morphology and growth of ESC, self-renewal, and potential differentiation into various cell types. The discovery of the iPSC, unhindered by the aforementioned limitations of ESC, introduces a viable alternative to ESC. More importantly, the applications of iPSC in the development of disease models such as neurodegenerative disorders greatly enhance our understanding of the pathogenesis of such diseases and also facilitate the development of clinical therapeutic strategies using iPSC generated from patient somatic cells to avoid an immune rejection. In this review, we highlight the advances in iPSCs generation methods as well as the mechanisms behind their reprogramming. We also discuss future perspectives for the development of iPSC generation methods with higher efficiency and safety.

Pluripotent stem cells and their use in hearing loss

Throughout its half a century of development, stem cell research has included two main fields: embryonic stem (ES) cell research and the reprogramming of body somatic cells. In the present review we focused on stem cell reprogramming and its relation with otolaryngology. The human body somatic cells are transformed into pluripotent cells by three basic methods: the somatic nuclear transfer method, the somatic cell fusion method (getting cellular pluripotent capacity in cellular reprogramming), and by transcription factors influencing the body somatic cells to generate reprogrammed induced pluripotent stem (iPS) cells. ES cells and iPS cells have pluripotency and differentiate into cells originating from the three germ layers; they are preferred for cellular treatment, drug development, and disease modeling research. Because of ethical restrictions in obtaining ES cells, iPS cells are an alternative pluripotent cell source and patient-specific autologous pluripotent cells are obtained by this method. Cellular treatment and regenerative medicine with pluripotent cells are currently developing and we aimed to raise awareness about this topic in our paper on using iPS cell technology in the biological treatment of hearing loss, which is an important area of research in otolaryngology.

Use of Human Embryonic Stem Cells in the Treatment of Thrombocytopenia: A Case Series: hESC therapy in Thrombocytopenia

Background: Treatment options such as corticosteroids, immunog- lobulins medicines, blood or platelet transfusions, or splenectomy are used for thrombocytopenia patients. In the present study, we reported the safety and efficacy of human embryonic stem cell (hESC) therapy in two patients with thrombocytopenia. The patients were presented with general weakness, and were unable to do their routine work. After the laboratory examinations, it was confirmed that both the patients were suffering from thrombocytopenia having platelet count 0.70m3 and 0.80m3, respectively.Methods and Findings: hESCs used in the present study were ob- tained from a single, spare, expendable, pre-implantation stage fertili- zed ovum taken during natural in vitro fertilization (IVF) and free from immunogenicity. After a single treatment session with hESCs, both patients showed an increase in blood platelet count and improvement in their condition. No adverse events (AEs) were reported.Conclusions: hESC therapy was found to be safe and effective. The study concluded that hESC therapy improved the condition of patients with thrombocytopenia.

Stem cell therapy in spinal cord injury: Hollow promise or promising science?

Spinal cord injury (SCI) remains one of the most physically, psychologically and socially debilitating conditions worldwide. While rehabilitation measures may help limit disability to some extent, there is no effective primary treatment yet available. The efficacy of stem cells as a primary therapeutic option in spinal cord injury is currently an area under much scrutiny and debate. Several laboratory and some primary clinical studies into the use of bone marrow mesenchymal stem cells or embryonic stem cell-derived oligodentrocyte precursor cells have shown some promising results in terms of remyelination and regeneration of damaged spinal nerve tracts. More recently,laboratory and early clinical experiments into the use of Olfactory Ensheathing Cells, a type of glial cell derived from olfactory bulb and mucosa have provided some phenomenal preliminary evidence as to their neuroregenerative and neural bridging capacity. This report compares and evaluates some current research into selected forms of embryonic and mesenchymal stem cell therapy as well as olfactory ensheathing cell therapy in SCI, and also highlights some legal and ethical issues surrounding their use. While early results shows promise, more rigorous large scaleclinical trials are needed to shed light on the safety, efficacy and long term viability of stem cell and cellular transplant techniques in SCI.

Thought Experiments, the Reliability of Intuitions, and Human Embryonic Stem Cell Research

Thought Experiments, the Reliability of Intuitions, and Human Embryonic Stem Cell Research

Improved Epilepsy and Speech Outcomes with Human Embryonic Stem Cell Therapy in Children with Cerebral Palsy

Title: Improved Epilepsy and Speech Outcomes with Human Embryonic Stem Cell Therapy in Children with Cerebral Palsy Introduction: CP is a group of permanent neurological disorders which is prevalent in children of neonatal age and is often associated with epilepsy and speech disorders. The various conventional treatments and therapies available so far are unable to treat these comorbidities. In this study, we aimed to evaluate 101 patients with CP having speech disorders and epilepsy. The patients were treated using hESC therapy and assessed by Gross Motor Function Classification System - Expanded and Revised (GMFCS – E & R) score. Materials and Methods: Patients were given hESCs via different routes of administration for duration of 8 weeks and evaluated before and after the treatment on the basis of their le

As the World Turns Catholicism and Embryonic Stem Cell Research

As the World Turns Catholicism and Embryonic Stem Cell Research

Human Embryos, Patents and Global Trade: Assessing the Scope and Contents of the Trips Morality Exception

Can a World Trade Organization (WTO) Member exclude an invention from patentability on the grounds of ordre public or morality whilst at the same time permitting the sale and distribution of the invention within its territory? This is a question raised by recent developments in Europe, where moral restrictions have been placed on the patentability of ‘uses of human embryos’, yet human embryonic stem cell (hESC) research, which involves the destruction of human embryos, is permitted and encouraged within numerous EU Member States, and indeed, also funded through the central EU science budget. This chapter assesses whether such an incoherent regulatory landscape would survive WTO scrutiny. The chapter argues that in general, if a WTO Member has not attempted to ban the commercial exploitation of a certain invention within its borders, measures prohibiting the patenting of that invention on moral grounds would likely be viewed as constituting an unjustified restriction on international trade. More concretely, it is suggested that the WTO Member would be found to be in violation of its obligation under the TRIPS Agreement to make patents available without ‘discrimination’ as to the field of technology.

“Em defesa da vida humana”: Moralidades em disputa em duas audiências públicas no STF

Resumo Neste artigo analisamos as formas da presença de moralidades católicas em duas audiências públicas realizadas no Supremo Tribunal Federal. A primeira refere-se ao julgamento da ação sobre a permissão do uso de células tronco embrionárias em pesquisas científicas; e a segunda, ao julgamento da ação que possibilitou a interrupção da gestação de fetos anencéfalos. Nas duas ações agentes vinculados à CNBB participaram do processo. Observamos as estratégias e dispositivos acionados por esses agentes, vinculados ao chamado bloco “pró-vida”, na constituição de seu argumento geral “em defesa da vida” nas duas audiências. Para compreender a disputa pelo convencimento nessas arenas, observaremos a controvérsia mais ampla, identificando os repertórios de justificação produzidos pelos agentes e blocos favoráveis às ações, especialmente referentes à categoriavida.