Stem Cell Science Research Articles

The 3rd National Festival & International Congress on Stem Cell & Regenerative Medicine.

Background and Aim: Stem cell technology was started in Iran in the late of 1990 by first hematopoietic stem cell transplantation in Tehran University of Medical Sciences and in less than a decade, Royan Institute started stem cell research followed by infertility treatment. Since then, different universities and research centers have focused on stem cells and regenerative medicine which resulted in publishing more than 2500 articles in journals indexed in PubMed as well as creating new ideas. The council of stem cell sciences and technologies in the vice presidency for science and technology started its activity ten years ago, with the aim of expanding education, research and development of human resources. Scientific opportunities in this field have been created by the integration of government and scientific communities. During this time, by the financial and spiritual support given by this center, research projects were carried out in more than 45 universities and institutes. Four Centers of Excellence for Stem Cell & Regenerative Medicine has been established in Royan, Tabriz, Shiraz, and Tehran to integrate scientific capacities human resources and laboratory equipment. Student Olympiads were held at the high school level, and the establishment of Student Research Centers in three provinces can be considered as the most influential activities for stem cell council. In recent years, recognizing the importance of promoting the culture of a knowledge-based economy, stem cell council also seeks to strengthen the knowledge-based companies by supporting and guidance of researchers and investors, as it has caused the number to increase to more than 75 titles. The council of stem cell sciences and technologies also organized two national festival and international congress, 70 symposiums, and several workshops to spread stem cell sciences and technology among the public. The first social network and science-specific messenger, across the country, has been launched in 2017 by the stem cell council promotion. The application as mentioned above would be a platform which can provide effective interactions among specialists in the field of stem cell sciences. Animal lab network is the other supported project by stem cell council. It gives an opportunity for the researchers to use various animal models and facilitate in vivo studies. Finally, the collaboration between Iran stem cell council and Iran FDA has led to the development of products regulations. In this regard, four cell-based products were licensed to enter the market. Now Iran is the first rank among Eastern Mediterranean and Middle East countries. The issues mentioned are part of the mission of the stem cell council which has been carried out until now.

Benchmarking Stem Cells and Transplantation in Psoriasis

Psoriasis is a chronic systemic inflammatory disease with several abnormalities in hematopoiesis. During the last 30 years, stem cell science was intensively studied, also in the field of psoriasis, to discover therapeutic modalities by reversing the unbalance in lymphopoiesis. In fact, available results in literature have reported psoriasis remission after stem cell transplantation. The present review summarizes the current knowledge on psoriasis, stem cells and transplantation.

Comparative genomic analysis of embryonic, lineage-converted, and stem cell-derived motor neurons

Advances in stem cell science allow the production of different cell types in vitro either through the recapitulation of developmental processes, often termed 'directed differentiation', or the forced expression of lineage-specific transcription factors. Although cells produced by both approaches are increasingly used in translational applications, their quantitative similarity to their primary counterparts remains largely unresolved. To investigate the similarity between in vitro-derived and primary cell types, we harvested and purified mouse spinal motor neurons and compared them with motor neurons produced by transcription factor-mediated lineage conversion of fibroblasts or directed differentiation of pluripotent stem cells. To enable unbiased analysis of these motor neuron types and their cells of origin, we then subjected them to whole transcriptome and DNA methylome analysis by RNA sequencing (RNA-seq) and reduced representation bisulfite sequencing (RRBS). Despite major differences in methodology, lineage conversion and directed differentiation both produce cells that closely approximate the primary motor neuron state. However, we identify differences in Fas signaling, the Hox code and synaptic gene expression between lineage-converted and directed differentiation motor neurons that affect their utility in translational studies.

Ethical and Safety Issues of Stem Cell-Based Therapy.

Results obtained from completed and on-going clinical studies indicate huge therapeutic potential of stem cell-based therapy in the treatment of degenerative, autoimmune and genetic disorders. However, clinical application of stem cells raises numerous ethical and safety concerns.In this review, we provide an overview of the most important ethical issues in stem cell therapy, as a contribution to the controversial debate about their clinical usage in regenerative and transplantation medicine.We describe ethical challenges regarding human embryonic stem cell (hESC) research, emphasizing that ethical dilemma involving the destruction of a human embryo is a major factor that may have limited the development of hESC-based clinical therapies. With previous derivation of induced pluripotent stem cells (iPSCs) this problem has been overcome, however current perspectives regarding clinical translation of iPSCs still remain. Unlimited differentiation potential of iPSCs which can be used in human reproductive cloning, as a risk for generation of genetically engineered human embryos and human-animal chimeras, is major ethical issue, while undesired differentiation and malignant transformation are major safety issues.Although clinical application of mesenchymal stem cells (MSCs) has shown beneficial effects in the therapy of autoimmune and chronic inflammatory diseases, the ability to promote tumor growth and metastasis and overestimated therapeutic potential of MSCs still provide concerns for the field of regenerative medicine.This review offers stem cell scientists, clinicians and patient's useful information and could be used as a starting point for more in-depth analysis of ethical and safety issues related to clinical application of stem cells.

Fake news portrayals of stem cells and stem cell research.

This study examines how stem cells and stem cell research are portrayed on websites deemed to be purveyors of distorted and dubious information. Content analysis was conducted on 224 articles from 2015 to 2016, compiled by searching with the keywords 'stem cell(s)' on a list of websites flagged for containing either 'fake' or 'junk science' news. Articles contained various exaggerated positive and negative claims about stem cells and stem cell science, health and science related conspiracy theories, and statements promoting fear and mistrust of conventional medicine. Findings demonstrate the existence of organized misinformation networks, which may lead the public away from accurate information and facilitate a polarization of public discourse.

Accelerating regenerative medicine: the Japanese experiment in ethics and regulation.

In 2014, the Japanese National Diet introduced new laws aimed at promoting the clinical translation of stem cells and regenerative medicine. The basic action of these laws is to allow the early introduction of regenerative medicine products into the Japanese market through an accelerated approval process, while providing patients with access to certain types of stem cell and cell-based therapies in the context of private clinical practice. While this framework appears to offer enormous opportunities for the translation of stem cell science, it raises ethical challenges that have not yet been fully explored. This paper critically analyzes this framework with respect to the prioritization of safety over clinical benefit, distributive justice and public trust in science and medicine. It is argued that the framework unfairly burdens patients and strained healthcare systems without any clear benefits, and may undermine the credibility of the regenerative medicine field as it emerges.

国際幹細胞学会（ISSCR）「幹細胞研究・臨床応用」ガイドラインの解説

国際幹細胞学会（ISSCR）「幹細胞研究・臨床応用」ガイドラインの解説

Inhibition of EZH2 Promotes Human Embryonic Stem Cell Differentiation into Mesoderm by Reducing H3K27me3.

SummaryMesoderm derived from human embryonic stem cells (hESCs) is a major source of the mesenchymal stem/stromal cells (MSCs) that can differentiate into osteoblasts and chondrocytes for tissue regeneration. While significant progress has been made in understanding of molecular mechanisms of hESC differentiation into mesodermal cells, little is known about epigenetic factors controlling hESC fate toward mesoderm and MSCs. Identifying potential epigenetic factors that control hESC differentiation will undoubtedly lead to advancements in regenerative medicine. Here, we conducted an epigenome-wide analysis of hESCs and MSCs and uncovered that EZH2 was enriched in hESCs and was downregulated significantly in MSCs. The specific EZH2 inhibitor GSK126 directed hESC differentiation toward mesoderm and generated more MSCs by reducing H3K27me3. Our results provide insights into epigenetic landscapes of hESCs and MSCs and suggest that inhibiting EZH2 promotes mesodermal differentiation of hESCs.

Regenerative engineering and advanced materials science

Abstract

\u201cA good collaboration is based on unique contributions from each side\u201d: assessing the dynamics of collaboration in stem cell science

The rise of ‘big biology’ is bringing academic and industrial scientists together in large consortia to address translational challenges in the life sciences. In order to assess the impact of this change, this paper examines the existing norms and styles of collaboration in one high profile translational domain; stem cell research. Data is drawn from qualitative interviews with academic and industry scientists working in a large European stem cell research project. Respondents discussed what they perceived as the main benefits and risks of collaborative research, what styles of collaboration they were familiar with, and what collaborative work in stem cell science normally involves. A wide range of materials, data, and expertise can be exchanged during collaborative work. Informal collaborations are governed by an ethos of reciprocity and mediated by trust while formal project agreements can provide a safe space for sharing between unfamiliar partners. These characteristics make stem cell research well suited to pre-competitive public-private ventures but translation of new products to market may be more challenging.

Usage of Stem Cell, Regenerative Medicine, Nanotechnology and Tissue Engineering Science Education to Improve Stem Cell and Nano-Science Literacy

Usage of stem cell regenerative medicine nanotechnology and tissue engineering science education to improve stem cell and nano science literacy

Stem‐Like Cells in Breastmilk for Hospitalized Preterm Infants

Breastmilk stem cells are a relatively new discovery in the scientific community. There are still many unknowns about their specific mechanisms of interaction; however, it has been hypothesized that their presence contributes to growth and development of the breastfed infant. Our research team is the first known team to enroll mothers of hospitalized preterm infants during the first few weeks of lactation and compare stem cell phenotypes and expression to mothers of healthy full‐term infants. The purpose of this study was to evaluate the feasibility of NICU breastmilk collection and the comparison of preterm and full‐term breastmilk cells. We enrolled mothers of preterm infants (n=7; range 26 4/7 – 34 5/7 weeks gestational age at birth) and mothers of healthy full‐term infants (n=4; range 39 5/7–40 5/7 weeks gestational age at birth). Flow cytometry and qRT‐PCR analysis were used to assess the prevalence of a variety of pluripotent and mesenchymal stem cell markers. Overall, cells with stem‐like characteristics were identified in both preterm and full‐term breastmilk samples. There was large variability among the amount of each stem cell phenotype present, as well as in the expression of specific markers. Preliminary results indicate that gene expression in the majority of the tested markers were significantly different between the preterm sample and the full‐term sample. In conclusion, there are individual differences in the cellular composition of breastmilk, and this variation results in differential expression of phenotypic markers and gene expression of breastmilk cells with multipotent and pluripotent characteristics. The science of breastmilk stem cells is new and there is future potential to use these easily accessible stem cells in regenerative medicine. Future studies will explore the relationship of breastmilk stem cell characteristics to neonatal health, most notably their regenerative and protective potential.Support or Funding InformationNational Association of Neonatal Nurses and Foundation for Neonatal Research and Education

Development of hydrogels for regenerative engineering.

The aim of regenerative engineering is to restore complex tissues and biological systems through convergence in the fields of advanced biomaterials, stem cell science, and developmental biology. Hydrogels are one of the most attractive biomaterials for regenerative engineering, since they can be engineered into tissue mimetic 3D scaffolds to support cell growth due to their similarity to native extracellular matrix. Advanced nano- and micro-technologies have dramatically increased the ability to control properties and functionalities of hydrogel materials by facilitating biomimetic fabrication of more sophisticated compositions and architectures, thus extending our understanding of cell-matrix interactions at the nanoscale. With this perspective, this review discusses the most commonly used hydrogel materials and their fabrication strategies for regenerative engineering. We highlight the physical, chemical, and functional modulation of hydrogels to design and engineer biomimetic tissues based on recent achievements in nano- and micro-technologies. In addition, current hydrogel-based regenerative engineering strategies for treating multiple tissues, such as musculoskeletal, nervous and cardiac tissue, are also covered in this review. The interaction of multiple disciplines including materials science, cell biology, and chemistry, will further play an important role in the design of functional hydrogels for the regeneration of complex tissues.

Big-Data-Driven Stem Cell Science and Tissue Engineering: Vision and Unique Opportunities

Achieving the promises of stem cell science to generate precise disease models and designer cell samples for personalized therapeutics will require harnessing pheno-genotypic cell-level data quantitatively and predictively in the lab and clinic. Those requirements could be met by developing a Big-Data-driven stem cell science strategy and community.

Infrastructural expectations: exploring the promise of international large-scale induced pluripotent stem cell banks

This paper investigates the recent emergence of several major projects to bank and distribute large numbers of human induced pluripotent stem cells (hiPSCs) for translational research. The conceptual framework of the sociology of expectations is applied to interrogate the promise underpinning these developments. An analytic distinction is made between expectations associated with the field of hiPSC research more broadly and those specifically invested in cell banks as a form of scientific infrastructure, with the focus predominantly on the latter element. Empirical data for the analysis comes from qualitative interviews with stem cell scientists involved in a major European hiPSC banking project. In order to unpack these expectations, parallels to previous infrastructures of dissemination will be highlighted, with an emphasis on the functions of circulating and securing the quality of biological research materials.

Menstrual Blood Banking-A Review

Stem cell science and therapies related to stem cell are making remarkable progress. Menstrual blood has always been a subject of study in different researches due to its easy availability. The possibility of isolation of stem cells from the menstrual blood and the umbilical cord blood cells has opened a new channel in stem cell research that can offer future therapeutic benefits to mankind. Several successful researches have shown the use of the stem cells derived from the endometrial blood for the treatments of different fatal diseases. The current breakthrough discovery that the menstrual blood contains stem cells that are proliferative and are capable of differentiating into different types of cells including cardiac cells, neural cells and into almost 9 types of tissues including heart, liver and lung, has opened a new field for therapeutic treatment.

The past, present and future of ligament regenerative engineering.

Regenerative engineering has been defined as the convergence of Advanced Materials Sciences, Stem Cell Sciences, Physics, Developmental Biology and Clinical Translation for the regeneration of complex tissues and organ systems. Anterior cruciate ligament (ACL) reconstruction necessitates the regeneration of bone, ligament and their interface to achieve superior clinical results. In the past, the ACL has been repaired with the use of autologous and allogeneic grafts, which have their respective drawbacks. Currently, investigations on the use of biodegradable matrices to achieve knee stability and permit tissue regeneration are making promising advancements. In the future, utilizing regenerative biology cues to induce an endogenous regenerative response may aid the enhancement of clinical ACL reconstruction outcomes.

Thyroid Stem Cells: Concept and Clinical Implications

Thyroid pathology is the commonest endocrine surgical problem encountered. However, the study of thyroid stem cells is relatively new in the field of stem cell research. Since the identification of thyroid stem cells in 1992, research interest in this area has been increasing mainly based on furthering our knowledge of the biology of these important cells that are thought to be responsible for tumourigenesis and propagation of cancers. This article reviews the current science and biology of thyroid stem cells and summarizes their potential role in the general management of thyroid disorders.

You can go your own way: State regulation of oocyte donation in California and New York

State regulation of oocyte donation in the context of human embryonic stem cell (hESC) research has increased since California’s landmark passage of Proposition 71 and the establishment of the first state-funded stem cell agency, the California Institute for Regenerative Medicine (CIRM). Scholarship has largely focused on California’s regulation of stem cell research as a patchwork of private sector and state regulations, reflecting major debates about the social contract for science. Given California’s political exceptionalism, how does examining alternative state histories, political structures, and institutions at the state level illuminate the ways that bio-innovation is being regulated in a federal regulatory vacuum? Examining state management of oocyte donation in the context of hESC research, this article considers New York and California as comparative sites of stem cell science regulation, which enriches our understanding of how regulation of stem cell science arises out of an engagement with representative politics and the private sector in the United States. Employing a process tracing of policy development in New York and California, this article highlights alternative democratic pathways to the management of oocyte donation in research contexts: given differences in direct democratic action, legislative representation, executive leadership, and publicly funded state stem cell research institutions, distinct regulatory outcomes occur with important bioethical implications for publics and participants in stem cell science at the state level.

Potential impact and controversy of stem cells in public health

Stem cells are versatile in the bodies which are able to both reproduce themselves and to produce more specialized cells. As such, they are of great potential values in repairing and regenerating damaged cells and tissues. Many different kinds of stem cells have been discovered. The most common are embryonic, foetal and adult stem cells. Stem cell research has the potential to provide an increased understanding of development and differentiation, as well as leading to treatments and cures for many diseases. They are important to the future of medicine and public health because with adequate research, stem cells have the potential to treat degenerative conditions through transplanting human stem cells into patients. With sufficient development of stem cell medicine, chronic diseases such as diabetes, heart disease, and Parkinson’s disease will be effectively managed. Embryonic stem cell (ESC) research has been a source of ethical, legal, and social controversy which has slowed the pace of stem cell science and shaped many aspects of its subsequent development.