Human Embryonic Stem Cells in Development, Volume 129, the latest release in the Current Topics in Developmental Biology series, highlights new advances in the field, with this new volume presenting interesting chapters on topics such as recapitulating pancreas development from human embryonic stem cells in a dish, modeling mammalian gastrulation with embryonic stem cells, and a section on what stem cells tell us about human germ cell biology. Each chapter is written by an international board of authors. Provides the authority and expertise of leading contributors from an international board of authors Presents the latest release in the Current Topics in Developmental Biology series
A discussion of all the key issues in the use of human pluripotent stem cells for treating degenerative diseases or for replacing tissues lost from trauma. On the practical side, the topics range from the problems of deriving human embryonic stem cells and driving their differentiation along specific lineages, regulating their development into mature cells, and bringing stem cell therapy to clinical trials. Regulatory issues are addressed in discussions of the ethical debate surrounding the derivation of human embryonic stem cells and the current policies governing their use in the United States and abroad, including the rules and conditions regulating federal funding and questions of intellectual property.
Recent advances in the fields of medicine and technology have led to the development of stem cell therapy. A stem cell is a cell that has the potential to develop into many different types of cell in the body. It has the ability to divide and copy itself and at least one other specialized type of cell. Stem Cells was written to provide information about the development of stem cell therapy, which can be used in the fields of research and medicine. The main goal of the book is to provide readers with an overview of the scientific facts about stem cells and its promising effects on the human body, as well as on the creation of new drugs and medicines. The book also highlights the ongoing clinical research into stem cells and lists the therapies whose effectiveness is being investigated. Many scientists argue that stem cell therapy will be of great help to patients and society if it is proven to be safe and effective. Explains in straightforward, non-specialist language the basic biology of stem cells and their applications in modern medicine and future therapy Includes extensive coverage of adult and embryonic stem cells both historically and in contemporary practice Richly illustrated to assist in understanding how research is done and the current hurdles to clinical practice
The aim of this project was to understand how the status of the mitochondria modulates the proliferation and other properties of human embryonic stem cells (hESC). The mitochondria dynamically modulate the cellular state through changes in the epigenome that dictate gene expression in response to environmental cues such as hormonal signaling and energetic status. It was necessary to first determine what, if any, differences existed between mitochondrial function in pluripotent cells and in somatic cells. To test the mitochondrial physiology in slow-growing hESC, we developed new technology to probe the bioenergetic status of the mitochondria in a miniscule amount of isolated mitochondria. In concert with the more conventional Oroboros respirometry system, we verified that the mitochondria in ESC are operating in a unique state distinct from that in somatic cells. Moreover, in addition to the activated expression of the hallmark pluripotency genes, there is a pattern of upregulated genes involved in mitochondrial biogenesis and in epigenetic modification that is distinct from differentiated cells. These data support the hypothesis that there is a difference in mitochondrial function between somatic cells versus pluripotent cells and that this difference underlies the important role of mitochondria in regulating the cellular state. Further, this thesis represents the first study of a sequence-independent heritable phenotype that is maintained and transmitted exclusively through the mitochondria of pluripotent hESC. To interrogate the role of mitochondria in pluripotent stem cells, we generated several groups of cybrids cells in which the only difference between them is the origin of their mitochondria. The organelles were derived from two separate pluripotent cell lines, H1 and H9, and were compared to those derived from two separate lines of normal adult lymphoblasts. The results show that many key characteristics of pluripotent cells were conserved exclusively in the cybrid lines generated from hESC including a conversion to more stem cell-like morphology and growth characteristics and a shift toward stem cell-like aerobic glycolysis. Additionally, the gene expression program was partially reprogrammed in these hESC cybrids to reflect some key characteristics of hESC, i.e. a unique mitochondrial regulatory network, enhanced transcription, and immortality.
There is much public interest in stem cells, but also much confusion and misinformation. Developmental biologist Jonathan Slack explains the biology behind stem cells - what they are what scientists do with them, what stem cell therapies are available today, and what can be expected to happen in the future.
Engineering Tissue from Human Embryonic Stem Cells: Differentiation of Embryonic Stem Cells to Clinically Relevant Populations: Lessons from Embryonic Development
Author: Daniel Cebo
Publisher: Independently Published
Recent advances in human embryonic stem cell (hESC) biology now offer an alternative cell source for tissue engineers, as these cells are capable of proliferating indefinitely and differentiating to many clinically relevant cell types. Novel culture methods capable of exerting spatial and temporal control over the stem cell microenvironment allow for more efficient expansion of hESCs, and significant advances have been made toward improving our understanding of the biophysical and biochemical cues that direct stem cell fate choices. Effective production of lineage specific progenitors or terminally differentiated cells enables researchers to incorporate hESC derivatives into engineered tissue constructs. Here, we describe current efforts using hESCs as a cell source for tissue engineering applications, highlighting potential advantages of hESCs over current practices as well as challenges which must be overcome
Human Stem Cell Technology & Biology: A Research Guide and Laboratory Manual integrates readily accessible text, electronic and video components with the aim of effectively communicating the critical information needed to understand and culture human embryonic stem cells. Key Features: An authoritative, comprehensive, multimedia training manual for stem cell researchers Easy to follow step-by-step laboratory protocols and instructional videos provide a valuable resource A must-have for developing laboratory course curriculums, training courses, and workshops in stem cell biology Perspectives written by the world leaders in the field Introductory chapters will provide background information The volume will be a valuable reference resource for both experienced investigators pursuing stem cell and induced pluripotent stem cell research as well as those new to this field.
Stem cells are unique cells that have both the capacity for self-renewal and, depending on their origin, the ability to form at least one, and sometimes many, specialised cell types of all three embryonic germ lineages - germ cells (endoderm, mesoderm and ectoderm), extra-embryonic tissue and trophoblast. Since the derivation of the first human embryonic stem cell (hESC) line in 1998, there has been substantial interest in the potential of these cells both for regenerative medicine and cell therapy, and as disease models for monogenic disorders. Aside from the need to improve derivation efficiency and further the understanding of the basic biology of these cells, the ability to work with hESC opens up three broad research areas. The first is the development of clinical grade culture systems with the aim of producing cell lines suitable for subsequent manipulation for therapy. The second is the opportunity to use these cells as a tool to study the earliest determinative events in mammalian development, such as the origins of patterning in the mammalian embryo. The third is the use of hESCs carrying clinically relevant genetic mutations as models for disease research and therapeutic target identification. The development of several methods of embryo manipulation tailored to the morphology of the blastocyst is described here, which resulted in the derivation of seven lines from four different procedures and provided the tools for subsequent research. Acknowledging that each laboratory in isolation is unlikely to derive sufficient lines to draw significant conclusions regarding manipulation methodology and culture parameters, an international collaboration was initiated with the aim of standardising the reporting of derivation and thus obtaining the maximum information from the generation of each new hESC line. To address the need for the development of clinical grade culture systems, alternative feeder cells were assessed for their suitability in hESC culture and derivation. Modified human foreskin fibroblasts and human amniotic epithelial cells (hAECs) were investigated, as both cell types can be fully qualified and validated. Whilst both were able to support the culture of existing lines, only the hAECs showed promise in supporting derivation. In addition, analysis of in-house and commercially available media showed that neither were physiologically optimal for the growth of inner cell mass (ICM) cells or putative hESC, as metabolite concentrations were in excess and subsequent catabolite levels exceeded known toxic levels. The timing and mechanisms establishing patterning and future polarity in the mammalian embryo remains a subject of intense debate. Here, the potential of single blastomeres to generate hESC was used as an assessment of pluripotency. The determination of the most appropriate day for attempting derivation was performed by assessing blastomere development and pluripotent marker expression, and the predicted success of derivation was considered in the light of division patterns. Putative stem-like cells were visible in several cultures. Furthermore, isolated blastomeres from two-, four-, and eight-cell embryos were analysed for the quantitative expression of multiple target genes known to be associated with lineage formation and the stem cell state. Analysis suggested that broad changes in gene expression were occurring with development stage. However, no consistent grouping structure for cells within embryos was observed, and no convincing pattern was seen when considering the individual embryo variance scores. Several approaches are discussed to differentiate between the biological and methodological variability in this experimental design. The suitability of hESC as models for genetic disease was studied following the derivation of two lines carrying Huntington disease (HD). Subsequent differentiation using a stromal co-culture neural induction protocol resulted in the establishment of a stable, highly proliferative cell population which was simple to culture and bank. The cells were of an astroglial phenotype, and therefore highly suited for subsequent studies regarding HD pathophysiology, as glial cells are severely affected in HD. During differentiation the CAG repeat size increased from 46 to 70, showing the salient feature of somatic instability of the huntingtin gene. Therefore this cell population provides a valuable tool in the study of disease pathogenesis and transmission.
This reader-friendly manual provides a practical "hands on" guide to the culture of human embryonic and somatic stem cells. By presenting methods for embryonic and adult lines side-by-side, the authors lay out an elegant and unique path to understanding the science of stem cell practice. The authors begin with a broad-based introduction to the field, and also review legal and regulatory issues and patents. Each experimental strategy is presented with an historical introduction, detailed method, discussion of alternative methods, and common pitfalls. This lab guide for researchers also serves as a textbook for undergraduate and graduate students in laboratory courses. • Offers a comprehensive introduction to stem cell biology and culture for medical and biology researchers investigating diagnostics and treatments for various diseases • Presents a historical introduction, discussion of alternative methods, and common pitfalls for basic and advanced experimental strategies • Includes new chapters devoted to iPS cells and other alternative sources for generating human stem cells written by the scientists who made these breakthroughs
Embryonic stem cells are one of the key building blocks of the emerging multidisciplinary field of regenerative medicine, and discoveries and new technology related to embryonic stem cells are being made at an ever increasing rate. This book provides a snapshot of some of the research occurring across a wide range of areas related to embryonic stem cells, including new methods, tools and technologies; new understandings about the molecular biology and pluripotency of these cells; as well as new uses for and sources of embryonic stem cells. The book will serve as a valuable resource for engineers, scientists, and clinicians as well as students in a wide range of disciplines.
Stem cell research has been a problematic endeavour. For the past twenty years it has attracted moral controversies in both the public and the professional sphere. The research involves not only laboratories, clinics and people, but ethics, industries, jurisprudence, and markets. Today it contributes to the development of new therapies and affects increasingly many social arenas. The matrix approach introduced in this book offers a new understanding of this science in its relation to society. The contributions are multidisciplinary and intersectional, illustrating how agency and influence between science and society go both ways. Conceptually, this volume presents a situated and reflexive approach for philosophy and sociology of the life sciences. The practices that are part of stem cell research are dispersed, and the concepts that tie them together are tenuous; there are persistent problems with the validation of findings, and the ontology of the stem cell is elusive. The array of applications shapes a growing bioeconomy that is dependent on patient donations of tissues and embryos, consumers, and industrial support. In this volume it is argued that this research now denotes not a specific field but a flexible web of intersecting practices, discourses, and agencies. To capture significant parts of this complex reality, this book presents recent findings from researchers, who have studied in-depth aspects of this matrix of stem cell research. This volume presents state-of-the-art examinations from senior and junior scholars in disciplines from humanities and laboratory research to various social sciences, highlighting particular normative and epistemological intersections. The book will appeal to scholars as well as wider audiences interested in developments in life science and society interactions. The novel matrix approach and the accessible case studies make this an excellent resource for science and society courses.
A critical review by prominent experts of both the cutting-edge of stem cell biology and the application of stem cells to endocrine diseases, including diabetes, infertility, and liver-associated metabolic disorders. The authors discuss current research to modify stem cells, develop an endocrine-like cell, and use adult bone marrow stem cells to treat autoimmune diseases, including endocrine-based autoimmune diseases. Topics of interest include a review of all stem cell subtypes and their characteristics, approaches to promoting endocrine development from stem cells, and evidence for endocrine cell function from stem cells. The authors also outline how best to develop preclinical studies that will determine the safety and efficacy of stem cell therapies for endocrine disorders.
This volume of Current Topics in Developmental Biology showcases the research and therapeutic value of stem cells, and is proof of the increasing maturation of the fields of regenerative and molecular medicine. Reviews include: * Therapeutic cloning and tissue engineering to produce functional replacement tissues. * The role of the protein a-synuclein in a host of neurodegenerative diseases, which may be the first to benefit from stem cell therapy. * The curious array of functions in eukaryotic DNA methyltransferase, crucial for normal development and at the core of epigenetics regulation. * Influencing stem cell differentiation with mechanical stress, another example of genes versus the environment. * The process of mammalian hematopoeisis, and inducing it in model organisms with embryonic stem cells. * The regulation of differential parental germline genetic imprinting, central for epigenetics. * The molecular function and regulation of the cystic fibrosis gene, critical for understanding the complete molecular mechanism of this devastating disorder, which might soon be treatable with stem cells. This volume comprehensively describes some of the most current issues in stem cell biology, and is an exciting preview of therapies that may soon be applied in the clinic. It is essential reading for researchers, clinicians, and trainees alike. * Therapeutic Cloning and Tissue Engineering * Structure and function of eukaryotic DNA methyltransferases * Mechanical Signals as Regulators of Stem Cell Fate * Molecular basis for the Chloride Channel Activity of CFTR and the Consequences of Disease Causing Mutations
Research into the field of stem cell biology has developed exponentially over recent years, and is beginning to offer significant promise for unravelling the molecular basis of a multitude of disease states. Importantly, in addition to offering the opportunity to delve deeply into the mechanisms that drive disease aetiology the research is realistically opening the doors for development of targeted and personalized therapeutic applications that many considered, until recently, to be nothing more that a far fetched dream. This volume provides a timely glimpse into the methods that have been developed to instigate, and the mechanisms that have been identified to drive, the process of nuclear reprogramming, chronicling how the field has developed over the last 50-60 years. Since the early 1950s a small number of notable experiments have provided significant impetus to the field, primarily the demonstration of reprogramming ability, first by the complex cytoplasmic milieu that constitutes the amphibian egg, then that of the mammalian egg, and finally that of the mammalian embryonic stem cell. Most recently, the demonstration that a limited pool of defined molecules is capable of reprogramming a multitude of cell types has provided massive impetus and facilitated transition towards realistic therapeutic application. We have therefore reproduced some of the key articles that elegantly document these dramatic stages of development of the field in an inclusive appendix to the book, for the benefit of readers keen to investigate the history of how the field of stem cell biology has evolved. Owing to the ever broadening nature of this field, and the incredible rate at which it is evolving, the main content of this volume focuses on areas that have shown significant movement in recent years, are most likely to translate into personalized therapeutic application, and thus provide greatest potential for significant impact on human health in the not too distant future. We recognize that research into many other disease states and cell types are all equally worthy of discussion. We would therefore like to acknowledge those researchers involved whose work we have not been able to include in this volume. Nuclear Reprogramming and Stem Cells will serve as a valuable resource for all researchers in the field of stem cell biology, including those just setting out on their career path as well as those already established in the field.
Human Embryonic Stem Cell Protocols contributes to progress in the field by investigating human embryonic stem cells (hES) and increasing our understanding of the regulation of their self-renewal capacity, commitment and differentiation along various lineages, and their potential utility in regenerative medicine applications. These hard-won protocols, all generously shared by experts in this field, support the continued isolation of additional hES lines as well as the development of improved culture conditions, countering the view that hES cells are difficult to maintain and use.
Unknown to most outside observers, from the earliest days of embryonic stem cell research through today's latest developments, Christian theologians have been actively involved with leading laboratory research scientists to determine the ethical implications of stem cell research. And contrary to popular expectation, these Christians have been courageously advocating in favor of research. Three of these dynamic theologians tell their story in Sacred Cells? Why Christians Should Support Stem Cell Research. Sacred Cells? takes readers through the twists and turns of stem cell development, providing a brief history of the science and an overview of the competing ethical frameworks people use in approaching the heated debate. Each new scientific advance, from the cloning of Dolly the sheep to the use of engineered cells in humans, had to be carefully considered before proceeding. Rejecting the widely held belief that the ethics of stem cell research turn on the moral status of the embryo, the authors carefully weigh a diversity of ethical problems. Ultimately, they embrace stem cell research and the prospect of increased health and well being it offers.
The SAGE Encyclopedia of Stem Cell Research, Second Edition is filled with new procedures and exciting medical breakthroughs, including executive orders from the Obama administration reversing barriers to research imposed under the Bush administration, court rulings impacting NIH funding of research based on human embryonic stem cells, edicts by the Papacy and other religious leaders, and the first success in cloning human stem cells. Stem cell biology is clearly fueling excitement and potential in traditional areas of developmental biology and in the field of regenerative medicine, where they are believed to hold much promise in addressing any number of intractable medical conditions. This updated second edition encyclopedia will expand on information that was given in the first edition and present more than 270 new and updated articles that explore major topics in ways accessible to nonscientists, thus bringing readers up-to-date with where stem cell biology stands today, including new and evolving ethical, religious, legal, social, and political perspectives. This second edition reference work will serve as a universal resource for all public and academic libraries. It is an excellent foundation for anyone who is interested in the subject area of stem cell biology. Key Features: Reader’s Guide, Further Readings, Cross References, Chronology, Resource Guide, Index A Glossary will elucidate stem cell terminology for the nonscientist Statistics and selected reprints of major journal articles that pertain to milestones achieved in stem cell research Documents from Congressional Hearings on stem cells and cloning Reports to the President’s Council on Bioethics, and more