Promise Of Stem Cell Research Research Articles

An Interview with Mary Ann Liebert, Publisher of Stem Cells and Development

An Interview with Mary Ann Liebert, Publisher of <i>Stem Cells and Development</i>

Global Solutions to the Challenges of Setting up and Managing a Stem Cell Laboratory

Keywords Stem cell laboratory establishment.Laboratorydesign.Laboratory operation.Good cell culture practice.Laboratory management.Standardization.Quality controlBackground and OriginIn recent years, stem cell research has made major contribu-tions to our understanding of biology. The ability toreprogramme somatic cells to stem cells of desired potencyhas made this exciting area of research accessible to almostevery laboratory, in spite of varying ethical, political andeconomic scenarios. The promise of stem cell research inmaking regenerative medicine accessible has further attractedclinicians, materials scientists, chemists, physicists and othernon-specialists to this field of research. While this situation isdesirable, the novice usually faces the daunting task of settingupandmaintainingastemcelllaboratory,oftenwithoutaccessto local expertise.Researchers allocate a significantamount ofresource to keep their approach technologically advanced.Deliveryofrobustandreliabledata(i.e.achievingreliableandreproducible stem cell cultures for experimentation) is oftenneglected.Thiscanresultindisruptionanddelayinlaboratorywork and at worst, wasted research resource and evenretractionofpublications.Thisdocumentlaysoutfundamentalissues to be addressed in the establishment of a stem cellculture laboratory. The aim is to provide guidance on ways toovercome many challenges to smooth operation, encounteredin varying climates and environments. Parts of this overvieware modeled on the Guidance on Good Cell Culture Practice[3] and should be considered as an ‘aide memoire’ tocomplement existing guidelines. This guidance originatedfrom experience gained by the authors in the establishment ofmultiple cell culture laboratories and training students indifferent countries with widely different environmentalconditions in Northern Europe and in India.ScopeThis document addresses the full range of issues that new aswell as established stem cell researchers charged with settingup a stem cell laboratory may face. It proposes solutions todealwithpotentialproblemsaheadoftime.Theaimistohelpincrease reproducibility of procedures, reduceuncertainties insupply, and help academics meet international scientific andethical requirements.IntroductionGood scientific practice and maintenance of high standardsof mammalian cell culture is important for any researchbased on the use of stem cell lines. Contributions to stemcell research are now global and include researchers andcountries that are relatively new to the field. One importantgoal is to establish consistent standards of scientific andtechnical competence in stem cell culture that will promotegood science and efficient use of research resources. Thispaper identifies generic guidance for establishment and

Introduction: immunopathology and the promise of stem cell research

During the last few years, stem cell technology has elicited a great deal of fascination, hope and controversy as have done other cell research programs. The primary aim of developing stem cells for medical application is to regenerate tissues and repair failing organs. In addition, stem cell research can be viewed as a key to addressing and understanding many of the most fundamental and basic questions in clinical biology. A better insight into early cell development will provide answers to the question why cells behave abnormally and generate pathologies such as cancer or autoimmune and degenerative diseases. The huge interest focussing on this research and its potentially therapeutic applications are evident from the large investment made by companies, governments and universities worldwide. In October and November 2010, the two first human trials of cell therapy by embryonic stem cell-derived injections for spinal cord injury and non-hereditary forms of blindness were approved by the FDA. The source of stem cells, however, remains a subject of debate. Taking into account genetic and immunological criteria, stem cells can be derived from either of the following:

Global Challenges in Stem Cell Research and the Many Roads Ahead

The field of stem cell research has grown to include a vibrant international community of scientists and clinicians who come from both academia and industry and who strive to shed light on the biology of these remarkable cells and find applications in drug discovery, disease modeling, and regenerative medicine.

Annual Research Review: The promise of stem cell research for neuropsychiatric disorders

The study of the developing brain has begun to shed light on the underpinnings of both early and adult onset neuropsychiatric disorders. Neuroimaging of the human brain across developmental time points and the use of model animal systems have combined to reveal brain systems and gene products that may play a role in autism spectrum disorders, attention deficit hyperactivity disorder, obsessive compulsive disorder and many other neurodevelopmental conditions. However, precisely how genes may function in human brain development and how they interact with each other leading to psychiatric disorders is unknown. Because of an increasing understanding of neural stem cells and how the nervous system subsequently develops from these cells, we have now the ability to study disorders of the nervous system in a new way – by rewinding and reviewing the development of human neural cells. Induced pluripotent stem cells (iPSCs), developed from mature somatic cells, have allowed the development of specific cells in patients to be observed in real time. Moreover, they have allowed some neuronal‐specific abnormalities to be corrected with pharmacological intervention in tissue culture. These exciting advances based on the use of iPSCs hold great promise for understanding, diagnosing and, possibly, treating psychiatric disorders. Specifically, examination of iPSCs from typically developing individuals will reveal how basic cellular processes and genetic differences contribute to individually unique nervous systems. Moreover, by comparing iPSCs from typically developing individuals and patients, differences at stem cell stages, through neural differentiation, and into the development of functional neurons may be identified that will reveal opportunities for intervention. The application of such techniques to early onset neuropsychiatric disorders is still on the horizon but has become a reality of current research efforts as a consequence of the revelations of many years of basic developmental neurobiological science.

The Promise of Stem Cell Research in Pigs and Other Ungulate Species

Despite two decades of effort, establishment of pluripotent embryonic stem cells (ESC) from ungulates such as cattle and pigs has remained an elusive goal, with true ESC only successfully isolated from rodents and primates. The many reports describing ESC-like cultures from other "difficult" species has largely depended upon adopting strategies successful for mouse and human and have not yet produced a cell type that both proliferated continuously in culture without differentiation and demonstrated full pluripotent potential. These difficulties may have been exacerbated in ungulates by the lack of specific markers exclusive to inner cell mass (ICM) and its derivative the epiblast and by unique features of their preimplantation development. Especially important may have been the choice of culture condition, including growth factors, for establishing and sustaining the ESC. Recent modifications to culture medium, notably the inclusion of particular protein kinase inhibitors, have permitted ESC derivation from rat and previously "non-permissive" mouse strains. These conditions appear to stabilize the biochemical networks that sustain pluripotency and to render the cells dependent upon LIF signaling. In addition, the recent successful generation of induced pluripotent stem cells (iPSC) from pig by procedures that should be easily adapted to other species, is also likely to advance the area quickly. The pig is a particularly desirable species to create pluripotent cell lines because of its value as a biomedical model in transplantation at a time when there is mounting pressure to rush stem cells to the clinic before their safety has been adequately tested in animals.

Stem Cells: Growth and Development…in Policy

any scientists and patient advocates cheered earlier this summer when the National Institutes of Health (NIH) released new guidelines for human embryonic stem cell (hESC) research. The guidelines came after President Obama’s March 2009 executive order lifting the restrictions on federal support for research using embryonic stem cells. Obama’s directive revoked the Bush administration’s restrictions and funding ban on hESC research, which had limited scientists to using only 21 approved cell lines out of about 700 in existence. The directive also ordered the NIH to issue new guidelines for hESC research, which were released in July 2009. These new guidelines specify that NIH funding can be provided for research on hESCs derived from human embryos “that were created using in vitro fertilization for reproductive purposes [but] were no longer needed for this purpose,” and were donated by individuals who were fully informed about embryo treatment and gave their voluntary, written consent to use the embryos for research. The guidelines also stipulate that there can be no financial inducements for embryo donations, and that NIH-funded research must remain separate from privately funded research. Additionally, the NIH will establish a working group of scientists and ethicists to review existing cell lines, determine their eligibility for federal funding, and post those hESCs eligible for federal funds in an online registry. The presidential directive greatly expands the research potential in this field, but Obama noted in his remarks about the order that the “full promise of stem cell research remains unknown, and it should not be overstated.” Many advocates of stem cell research agree: Much more stem cell research will take place, yet much more policy work still awaits action. The spotlight is currently on the NIH working group. This is because until the NIH determines which cell lines are eligible for federal funding, hESC research remains on hold and, as of early September 2009, the NIH registry was still empty. Alan Smith, senior research scientist at Stemina Biomarker Discovery (a metabolomics company in Madison, Wisconsin), says that this void in the registry is a major concern for industry because it is slowing efforts to build new collaborations with other companies that are using yet-to-beapproved cell lines and to spur innovations in stem cell research. It is unclear when new stem cell lines will be entered into the registry—no timeline has been announced—but some researchers are concerned that the addition of the new lines may take years. Other pressing policy issues remain. Some analysts have suggested that the government focus on developing a coalition among all the entities that work on stem cells, perhaps by supporting the formation of geographic innovation hubs. Such a large-scale collaboration between universities and industries could be transformative for the field of regenerative medicine. Other experts, such as Jonathan Moreno, a senior fellow at the Center for American Progress, believe that the next grand policy challenge will be to develop guidelines for

Change in Federal Stem Cell Funding Policy Spurs Interest in Field

T he recent action by the Obama administration to overturn restrictions on federal funding for embryonic stem cell research is expected to breathe new life into the field. The change in policy, which was made offi cial on March 9, lifted the ban on the use of federal funds for any research involving human embryonic stem cell lines established after August 9, 2001, when then-President George W. Bush announced an executive order creating the restrictions. A 1996 law still bans the use of federal funds in the destruction of a human embryo, a necessary step in creating such cell lines, but those created with private or state funding are now eligible to be used in federally funded projects. “At this moment, the full promise of stem cell research remains unknown, and it should not be overstated,” said President Barack Obama, announcing his executive order overturning Bush’s. “But scientists believe these tiny cells may have the potential to help us understand, and possibly cure, some of our most devastating diseases and conditions ... Parkinson’s, cancer, heart disease, and others that affect millions of Americans and the people who love them.” The mention of cancer cheered many oncologists in particular. But more broadly, the change in policy is an enormous morale booster for many investigators, according to stakeholders across the nation, who say they have begun to see an uptick of interest among young scientists since the new president took offi ce in January. “The science itself has now been given a huge signal that this fi eld is open for business by the federal government, and so young people in particular who were steering away from this fi eld will now say, ‘Okay, no problem, I will be able to go into this fi eld and do my work because it won’t be a dead end, ’ ” said Susan Solomon, chief executive offi cer of the New York Stem Cell Foundation, which was established to raise private funding for stem cell research. On the West Coast, the California Institute of Regenerative Medicine (CIRM), the umbrella for that state’s substantial funding effort, is also seeing renewed interest among young scientists, said CIRM President Alan Trounson, Ph.D. “We get a lot of questions, people writing to us, ringing us up, asking how can they get into stem cell research,” he said. That is in stark contrast to the past 8 years, when the fi eld “had nobody going into it except for folks in California and a very small group of researchers elsewhere at elite institutions or ones that we could fi nd or fund,” Solomon said. “There were maybe 150 people or so in the East Room on Monday when a bunch of us were down there with the president for the signing,” she added. “If it had been a 500-person room, you would have had everybody who is doing any serious work with embryonic stem cells in that room.”

Ethical issues in stem cell research and treatment

The incredible promise of stem cell research to at minimum advance scientific understanding and perhaps ultimately to treat persons with devastating diseases gives moral force to efforts to conduct this research. However, stem cell research has been riddled with ethical questions, in part because the predominant methods being used to derive or attempt to derive human embryonic stem cells require destruction of the embryo. Nevertheless, the ethical debates surrounding human embryonic stem cell research have not been solely related to those associated with the embryo. For instance, the creation of chimeras in some stem cell research has elicited concerns. Oocyte harvesting, which is essential to the creation of human embryonic stem cells raises concerns related to safety of the donor. Other important ethical issues relate to informed consent of both donors of gametes and embryos as well as recipients of stem cells and stem cell products. Further, there has been some concern related to the commercialization of the process, justice, and the responsible conduct of research. In addressing the ethical issues associated with human embryonic stem cell research, it is important to note that they are being deliberated in a setting where scientific excitement is high, there are extraordinarily powerful arguments for access to investigational treatments, and the financial, moral and political stakes are great. In an attempt to minimize the ethical issues associated with human embryonic stem cell research so important research can proceed, professional groups have issued guidelines for the ethical conduct of this research and its oversight. Systematic data regarding these efforts should be collected in order to enhance the likelihood that they meet their ethical goals.

Stem cell century: law and policy for a breakthrough technology

The explosion of interest in stem cell research raises a raft of controversial policy questions. When should human embryos be used to create stem cells? Should cloning be outlawed? Should egg and tissue donors be paid? Should we allow scientists to patent stem cells? Is the government entitled to a portion of the revenue from stem cell technology created with public funds? How should the regulators and courts balance the competing goals of access to revolutionary treatments and protection of the public from unknown risks? Russell Korobkin, with contributions from Stephen R. Munzer, provides the first thorough discussion and analysis of these and other unsettled questions of law, policy, and ethics that surround stem cell science. His clear and concise description of complex problems coupled with logical and well-balanced conclusions makes this volume essential reading for all Americans, general readers and experts alike, interested in the promise of stem cell research and the future of regenerative medicine.

Cell of cells: The global race to capture and control the stem cell

Human embryonic stem (hES) cell research, a burgeoning area of medical inquiry, has been lauded by scientists, patient advocates, and members of the general public for its potential to cure many of today’s most dreaded diseases. Cynthia Fox’s Cell of cells: the global race to capture and control the stem cell presents the travails of stem cell researchers the world round and the vicissitudes of the patients who depend on them. It is a travelogue that provides the background of the work, people, and places involved in what is an exciting race to be first to realize the promise of stem cell research. It is a well-written book with material for the casual reader wanting to know more about the subject as well as for those with a greater familiarity with the topic who prefer more scientific detail. The book provides an overview of the science and politics surrounding this topic. Since hES cell research requires the destruction of human embryos, it has divided the religious conservative and scientific communities. Scientists see the potential to treat many life-threatening diseases while conservatives argue that these cells are still the foundations of human life and therefore have a right to life. Right-to-life supporters have been able to politicize this issue and hence place restrictions on stem cell research in America that will likely result in America falling behind in this scientific area. The key attribute of hES cells that makes them critical weapons in the fight against debilitating diseases is their ability to regenerate any and all of the body’s myriad cells and tissues. From alleviating common ailments such as rheumatoid arthritis to treating feared killers, including cancer, stroke, and heart disease, stem cells have the potential to restore wellness. The reader travels around the world as Fox reports on the international race to use stem cells successfully — illustrating mundane problems such as sand in Petri dishes in the Sahara and describing an Israeli lab that narrowly escaped a terrorist bomb. Fox also demonstrates the often cooperative nature of this area of research, even when the scientists involved hold different and opposing religious and political beliefs. In her writing, Fox adds a human dimension to the topic of stem cells. While she covers the scientific aspects of stem cell research, she also depicts the people involved, their lives and hopes and struggles. They live in different societies, in different environments. One of the most eye-opening sections of the book, titled “Biopolis,” describes research in Singapore, where some of the world’s most talented scientists have been recruited to work in state-of-the-art laboratories. Singapore has reportedly spent $1.5 billion on national stem cell research initiatives. It is easy to feel the passion that this scientific race engenders. Fox also makes the subject of stem cell research exciting through her descriptions of the efforts to condition a patient so that a donor organ will be accepted rather than rejected. She reviews the status of cloning and how its useful applications are expanding. The author also addresses the rise and fall of Woo-Suk Hwang, the South Korean researcher who claimed astonishing advances in stem cell research with his publications in major scientific journals. His career came to an abrupt end when it was made public that he had fabricated many of his results and had breached ethical guidelines when he paid women to donate their eggs for research. Fox proves to be a good storyteller. The book is filled with narratives that serve to increase the reader’s interest in science. Fox keeps the scientific facts and jargon to a minimum yet still gives the reader relevant information. Her pictorial descriptions of foreign settings are wonderful. Fox paints extremely vivid (at times a bit too graphic) images of places and people, and the stories are often suspenseful. She attempts to provide a plethora of lab findings; however, peer-reviewed scientific research is reported alongside limited commentaries and rhetoric that have not yet been critiqued via traditional channels by the conventional scientific community. Unfortunately, Cell of cells does not add much that is new. However, it makes one think about the immense possibility science holds for society. It tells a great story, one that unfortunately has not yet ended with success. But the struggle is important; it makes scientific research exciting. Aspiring students of science would benefit from this book, both as stimulation and as an example of the kinds of approaches undertaken in this particular scientific endeavor. The restrictions placed on hES cell research by religious groups will only delay success (assuming that there will be success at the end of this road). Fox’s book is an excellent introduction to the field of stem cell research and makes for interesting and entertaining reading.

Technology for a Sustainable Tomorrow

Editor's note: This is the last installment in a yearlong series designed to stimulate discussion in research and development. The series is one of several actions taken by the SPE R&amp;D Advisory Committee to encourage R&amp;D development and discussion. Please send any questions, comments, or ideas to vik.rao@halliburton.com. The Technology Tomorrow Series, comprising articles published in JPT during 2006 and 2007, is available as a collection on OnePetro (SPE-160929-JPT. The oil and gas industry faces an interesting future, likely in unprecedented fashion. Peak-oil theorists have surfaced from time to time, so the current discussion of that topic is not new. But what is new is that we are in a demand environment driven by the economies of China and India, with sustained growth and no signs of letting up. Additionally, anthropogenic origins of global warming are acquiring currency to the point where all the major oil companies now state their support for curbing CO2 emissions. All these elements converge to paint a very different picture of the energy world than ever before, one in which serious consideration is given to potential sources of energy previously regarded as mere fanciful conjecture, such as transport liquids from grass. The debate is no longer about producing enough energy to meet demand, but about producing hydrocarbons and energy in a sustainable manner. At the same time, it is also about producing more environmentally friendly fluids for transportation and power. Fig. 1 shows the Energyfiles estimate of future oil production, demonstrating the decline in conventional oil production with the shortfall made up by unconventional hydrocarbons and synthetic sources. Regardless of the accuracy of this estimate, it is clear that the industry will respond with a multipronged effort that will include the following elements. Increasing Ultimate Recoveries. In his April 2006 "Technology Tomorrow" article in JPT, Nansen Saleri of Saudi Aramco estimated that a modest increase in ultimate recoveries would provide 1 trillion bbl of hydrocarbons. He also suggested that the road to this goal would be paved by advances in reservoir understanding, intelligent wells, and improved lift. The most intriguing of his proposals is that of advanced understanding of the physical and chemical processes at the pore throats, going so far as to suggest that the breakthroughs here could be akin to the promise of stem cell research in the study of curing human diseases. An effort such as that will need more active involvement from the scientific community. This call to scientific arms needs to be taken up by petroleum engineering departments every where, in particular by seeking collaboration with basic science departments. I anticipate lively debate on this topic at the SPE Research and Development (R&amp;D) Conference on 26–27 April in San Antonio. Furthermore, the R&amp;D Advisory Committee is organizing a session at the American Assn. for the Advancement of Science (AAAS) regional meeting to be dedicated to a discussion of the challenges facing our industry, with the objective of exciting the imagination of the basic scientists assembled. We hope that the deliberations will be of sufficient value to merit a report in the AAAS flagship journal Science. The AAAS meeting will be held 18–21 April at the U. of Houston Clear Lake campus.

Canada’s Stem Cell Corporation: Aggregate Concerns and the Question of Public Trust

This paper examines one nascent entrepreneurial endeavour intended by Canada’s Stem Cell Network to catalyze the commercialization of stem cell research: the creation of a company called “Aggregate Therapeutics”. We argue that this initiative, in its current configuration, is likely to result in a breach of public trust owing to three inter-related concerns: conflicts of interest; corporate influence on the university research agenda; and the failure to provide some form of direct return for the public’s substantial tax dollar investment. These concerns are common to many efforts to commercialize academic science but are rendered particularly acute in this case given the therapeutic promise of stem cell research and the considerable number of resources related to stem cell research in Canada, which Aggregate Therapeutics is expected to pool. We do, however, believe that the company can be altered to guard against a violation of the public’s trust, and so we present concrete modifications to its structure, which we contend should be given immediate consideration.

The Politics and Promise of Stem-Cell Research

On July 19, President George W. Bush vetoed a bill that would have allowed a modest extension of embryonic stem-cell research. Dr. Robert Schwartz writes that this veto will result in a terrible waste: tens of thousands of fertilized eggs will be destroyed without a single one being permitted to contribute to our knowledge of cell differentiation.

George Daley, MD, PhD, Talks About the Clinical Promise of Stem Cell Research

George Daley, MD, PhD, Talks About the Clinical Promise of Stem Cell Research

Implications of cloning technique for reproductive medicine

The birth of Dolly following the transfer of mammary gland nuclei into enucleated eggs established cloning as a feasible technique in mammals, but the moral implications and high incidence of developmental abnormalities associated with cloning have induced the majority of countries to legislate against its use with human gametes. Because of such negative connotations, restrictive political reactions could jeopardize the therapeutic and scientific promise that certain types of cloning may present. For example, in addition to its proposed use as a way of generating stem cells, the basic technique of nuclear transplantation has proven useful in other ways, including its application to immature eggs as a new approach to the prevention of the aneuploidy common in older women, and for some recent advances in preimplantation genetic diagnosis. Thus, while attempts at reproductive cloning in man would seem premature and even dangerous at present, this field will require rational rather than emotional reactions as a basis for legislation if the therapeutic promise of stem cell research and the experimental potential of nuclear transplantation techniques are to be fully realized.

The ethics of human stem cell research.

The medical and clinical promise of stem cell research is widely heralded, but moral judgments about it collide. This article takes general stock of such judgments and offers one specific resolution. It canvasses a spectrum of value judgments on sources, complicity, adult stem cells, and public and private contexts. It then examines how debates about abortion and stem cell research converge and diverge. Finally, it proposes to extend the principle of "nothing is lost" to current debates. This extension links historical discussions of the ethics of direct killing with unprecedented possibilities that in vitro fertilization procedures yield. A definite normative region to inhabit is located, within a larger range of rival value judgments. The creation of embryos for research purposes only should be resisted, yet research on "excess' embryos is permissible by virtue of an appeal to the "nothing is lost" principle.