Tag: induced pluripotent stem cells

Bioethics News

Book Review: Cells Are The New Cure (BenBella Books, Inc., 2017). ISBN 9781944648800.

$26.95. Reviewed by Michael S. Dauber, MA

 

Cells Are The New Cure, written by Robin Smith, MD, and Max Gomez, PhD, is a book about the history of medical research on cells, both human and non-human, and recent developments in these techniques that have made cellular medicine one of the most promising fields for therapeutic exploration. While the book’s title suggests an exclusive focus on the healing aspects of genetic modification and human stem cell therapy, the text is much more than that: it is a roadmap for understanding the origins of such techniques, the current state of affairs in cellular and genetic therapies, the administrative landscape investigators must traverse in conducting research, and the areas in which we still need to make progress.

Smith and Gomez make an argument that is structurally simple yet gripping: they suggest that targeted therapies involving stem cells and genetic modifications are the future of medicine by pointing to the immense amount of studies in those fields that have yielded beneficial results. While many readers might acknowledge this fact even before reading the book, many may not be aware of the full extent of the knowledge we have gained from research on cells and genetics, or the myriad ways this knowledge has been applied. Of course, Smith and Gomez cover the big diseases that most people think of when imagining medical research: cancer, heart disease, neurodegenerative conditions, etc. However, the book also contains detailed information about how we age, what may cause certain allergies, how the body repairs itself, and the ways stem cell therapies, genetic editing techniques, and other complex medicines that build on these methods can be used to treat these conditions.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

Bioethics Blogs

No Pain, All Gain: The Case for Farming Organs in Brainless Humans

Guest post by Ruth Stirton, University of Sussex (@RuthStirton) and David Lawrence, Newcastle University (@Biojammer)

It is widely acknowledged that there is a nationwide shortage of organs for transplantation purposes.  In 2016, 400 people died whilst on the organ waiting list.  Asking for donors is not working fast enough.  We should explore all avenues to alleviate this problem, which must include considering options that appear distasteful.  As the world gets safer, and fewer young people die in circumstances conducive to the donation of their organs, there is only so much that increased efficiency in collection (through improved procedures and storage) can do to increase the number of human organs available for transplantation. Xenotransplantation – the transplantation of animal organs into humans – gives us the possibility of saving lives that we would certainly lose otherwise.

There are major scientific hurdles in the way of transplanting whole animal organs into humans, including significant potential problems with incompatibility and consequent rejection.  There is, however, useful similarity between human and pig cells, which means that using pigs as the source of organs is the most likely to be viable.  Assuming, for the moment, that we can solve the scientific challenges with doing so, the bigger issue is the question of whether we should engage in xenotransplantation.

A significant challenge to this practice is that it is probably unethical to use an animal in this way for the benefit of humans. Pigs in particular have a relatively high level of sentience and consciousness, which should not be dismissed lightly. 

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

Bioethics Blogs

Creative Minds: A Transcriptional “Periodic Table” of Human Neurons

Caption: Mouse fibroblasts converted into induced neuronal cells, showing neuronal appendages (red), nuclei (blue) and the neural protein tau (yellow).
Credit: Kristin Baldwin, Scripps Research Institute, La Jolla, CA

Writers have The Elements of Style, chemists have the periodic table, and biomedical researchers could soon have a comprehensive reference on how to make neurons in a dish. Kristin Baldwin of the Scripps Research Institute, La Jolla, CA, has received a 2016 NIH Director’s Pioneer Award to begin drafting an online resource that will provide other researchers the information they need to reprogram mature human skin cells reproducibly into a variety of neurons that closely resemble those found in the brain and nervous system.

These lab-grown neurons could be used to improve our understanding of basic human biology and to develop better models for studying Alzheimer’s disease, autism, and a wide range of other neurological conditions. Such questions have been extremely difficult to explore in mice and other animal models because they have shorter lifespans and different brain structures than humans.

Kristin Baldwin

Kristin Baldwin

The focus of Baldwin’s work will be the thousands of proteins, called transcription factors, that switch genes on and off in our cells and play key roles in determining cell fate. Groundbreaking research several years ago in the lab of Marius Wernig at Stanford University, Palo Alto, CA, established that forcing the activation of three preselected transcription factors in mature skin cells, or fibroblasts, could convert them into neurons [1]. Baldwin wondered whether greatly expanding the list of transcription factors might produce a diverse array of neuronal subtypes.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

Bioethics News

Ten years since the discovery of iPS cells. The current state of their clinical application

Photo Neurons derived from human iPS cells Stem Cells Australia

Background

Few biomedical discoveries in recent decades have raised so many expectations as the achievement of adult reprogrammed cells or induced pluripotent stem (iPS) cells.1

Pluripotent cells are obtained from adult cells from various tissues that, after genetic reprogramming, can dedifferentiate to a pluripotency state similar to that of embryonic cells, which allows for subsequent differentiation into different cell strains.2,3

In our opinion, this discovery is relevant not only to biomedical issues but also to ethical ones, given that iPS cells could replace human embryonic stem cells (see HERE) – whose use raises numerous ethical problems – in biomedical experimentation and in clinical practice. However, after the last 10 years, the use of iPS cells has still not been clarified. A number of expectations have been met, but other mainly clinical expectations are still far from being achieved.

Current research limitations with iPS cells

There is a notable low efficacy in the techniques employed for obtaining a sufficient proportion of iPS cells, which represents a difficulty in its clinical application.4  Another limitation is the incomplete reprogramming, which depends on the type of cell employed,5 and the problems of mutagenesis resulting from inserting exogenous transcription-factor coding genes, which can cause tumors in the employed cells used.6 Recent studies aim to mitigate this effect.7 A clinical trial for treating macular degeneration with retinal pigment epithelium cells derived from autologously obtained iPS cells has recently been halted.8 After an initially successful experience with the first treated patient, the genetic sequencing of the iPS cells obtained from the second patient revealed mutations in 3 different genes, one of which was classified as oncogene in the Catalogue of Somatic Mutations in Cancer.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

Bioethics Blogs

Regenerative Medicine: Making Blood Stem Cells in the Lab

Caption: Arrow in first panel points to an endothelial cell induced to become hematopoietic stem cell (HSC). Second and third panels show the expansion of HSCs over time.
Credit: Raphael Lis, Weill Cornell Medicine, New York, NY

Bone marrow transplants offer a way to cure leukemia, sickle cell disease, and a variety of other life-threatening blood disorders.There are two major problems, however: One is many patients don’t have a well-matched donor to provide the marrow needed to reconstitute their blood with healthy cells. Another is even with a well-matched donor, rejection or graft versus host disease can occur, and lifelong immunosuppression may be needed.

A much more powerful option would be to develop a means for every patient to serve as their own bone marrow donor. To address this challenge, researchers have been trying to develop reliable, lab-based methods for making the vital, blood-producing component of bone marrow: hematopoietic stem cells (HSCs).

Two new studies by NIH-funded research teams bring us closer to achieving this feat. In the first study, researchers developed a biochemical “recipe” to produce HSC-like cells from human induced pluripotent stem cells (iPSCs), which were derived from mature skin cells. In the second, researchers employed another approach to convert mature mouse endothelial cells, which line the inside of blood vessels, directly into self-renewing HSCs. When these HSCs were transplanted into mice, they fully reconstituted the animals’ blood systems with healthy red and white blood cells.

As reported in Nature, both teams took advantage of earlier evidence showing that HSCs are formed during embryonic development from budding endothelial cells in the aorta.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

Bioethics Blogs

The Ethics of In Vitro Gametogenesis

Françoise Baylis comments on the ethics of using gametes derived from human induced pluripotent stem cells for future human reproduction.

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A recent New York Times article, provocatively titled “Babies from Skin Cells? Prospect is Unsettling to Some Experts,” has once again drawn attention to controversial research by scientists at Kyushu University in Japan who succeeded in making fertile mouse pups using eggs created through in vitro gametogenesis (IVG). This is a reproductive technology that involves creating functional gametes (sperm and eggs) from induced pluripotent stem cells. Induced pluripotent stem cells are cells derived from adult body cells (such as skin cells) that have the ability to become other body cells including reproductive cells (sperm and eggs).

Supporters of this reproductive technology eagerly anticipate similar research in humans. Indeed, enthusiasts are quick to trumpet the potential benefits of in vitro gametogenesis. These benefits fall into three general categories.

First, we are told that research to derive human gametes from induced pluripotent stem cells is important for basic science. It will advance our understanding of gamete formation, human development, and genetic disease. In turn, this increased understanding will create new options for regenerative medicine.

Second, we are told that this research will allow clinicians to improve fertility services. For example, with in vitro fertilization (IVF), women typically have to undergo hormonal stimulation and egg retrieval. This can be onerous in terms of the time required for interviews, counseling, and medical procedures. It can also be harmful. Potential psychological harms include significant stress and its sequelae.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

Bioethics News

Stem cell research. The two sides of the coin

Science facing market

The “heads” of stem cell research

Stem cells today represent a great hope for the future of regenerative medicine due to their ability to differentiate into cell lines of almost any tissue, making them a promising therapeutic option for many diseases.

These pluripotent cells are found in embryonic and also in adult tissues. Their isolation and culture in specific media may lead to the development of tissues that are useful in regenerative therapies for conditions such as heart disease, myelopathies, diabetes, nerve injuries, retinopathies, etc. After their isolation, they are injected directly into the tissues to be regenerated, so that the stem cells differentiate into cells of these same tissues.

A third way of obtaining pluripotent cells is that described by Yamanaka 10 years ago, a finding for which he was awarded the Nobel prize in Medicine. Starting from a differentiated adult cell, Yamanaka managed to find a way of “dedifferentiating” it so that it returned to its pluripotent state, to then “redifferentiate” it into a particular cell line with therapeutic utility. These are known as iPS or induced pluripotent stem cells.

Similarly, tissues that simulate the function of certain organs have been reproduced in vitro from stem cells, and could, in the future, be an alternative to current organ transplantation.

The current state of the clinical application of stem cells remains uncertain. Although successful outcomes have been reported in some fields, such as cardiology and haematology, many clinical trials and therapeutic applications have failed due to problems arising in the differentiation processes and the appearance of tumours.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

Bioethics Blogs

All we like SHEEFs, Part 2

Carrying on with last week’s musings…

In thinking further, I think my attempt was confused by conflating the moral status of a SHEEF—a synthetic human entity with embryo-like features, something more than a clump of cells of human origin, but less than a human being—with reasons why I might want to hold that nobody should ever make certain sorts of SHEEFs.

Again, SHEEFs are human, not non-human.  But they may not command a “right to life” in every instance.

I would return to a statement I made last week, that any totipotent human entity, that is, any human entity capable of developing into a full human being under the right circumstances, should be accorded a full human right to life from the moment he or she comes into existence.  We other humans ought to give him or her a chance to live, care for him or her as one of us, grant him or her any research protections extended to human research subjects in general, and so on.  So-called human “embryos in a dish” would be in this group.

The same cannot be said for individual human cells, including human gametes formed from cells like induced pluripotent stem cells.  There may be arguments why those ought not to be produced, but that is for another time.

I would not say that a laboratory-created or sustained human heart, for example, ought to be protected from instrumental uses, including destruction for the research enterprise.  I think I would want to argue that we humans ought not make such a thing as part of a human-non-human animal hybrid, but again, that’s a different argument.  

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

Bioethics Blogs

The moral problem of manufacturing children

Mark McQuain’s post yesterday about the moral concerns raised by some of the new things such as in vitro gametogenesis in conjunction with human induced pluripotent stem cells being developed in the field of artificial reproductive technology made me think of something that Leon Kass had written in the early days of in vitro fertilization. In the early years when in vitro fertilization was being hailed as an advance which would provide the ability to have their own biological children to many couples who were suffering from infertility for whom no effective treatment had previously been available, he and others warned that we needed to be morally cautious about this new technology because it would lead to us thinking of children as something that we could manufacture. A significant part of what he and others were saying was that up until that time the conception of children had always been something that was shrouded in a certain degree of mystery. There was an understanding of the miraculous nature of the creation of a new human being, and by those who had a sense of the divine origin of human beings it was understood that every child was a gift from God. This was something that impacted how children were viewed in society and individually by their parents. If each child was a gift from God, made in his image, and received through the natural consequence of the expression of the love the couple had for each other, we could understand that each child should be loved unconditionally.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

Bioethics Blogs

Do Extended Pluripotent Stem Cells Raise Ethical Issues?

On April 6, the journal Cell published work (subscription or online article purchase required) from the Salk Institute in San Diego, in which scientists have created a new “reprogrammed” stem cell.

These cells are called “extended pluripotent stem cells” or “EPS” cells.  They are different from embryonic stem (ES) cells, which are removed from intact embryos that arise from fertilization—typically requiring specific creation and destruction of an embryo.   Of course, ES cells can be human or non-human, depending on the source.

EPS cells are similar to “induced pluripotent stem cells,” or iPSCs, invented in 2006.  The latter are generated from adult skin cells that have been reprogrammed, using genetic alterations.

EPS cells may be made by reprogramming ES cells or skin cells or, if I understand the work correctly, iPSCs.  In this case, the reprogramming is done with a cocktail of chemicals in the lab.

But EPS cells are more capable than iPSCs.  Unlike iPSCs, which can give rise to many different types of cells but not all—including not a placenta and not an entire intact new individual—EPS cells can do all of that.  They are totipotent, meaning they can make all the cells of an individual from their species.  Moreover, they are quite long-lived in the laboratory.  EPS cells from one species—e.g., humans—can be placed into non-human (e.g., mouse) embryos to make hybrid animals that, it appears, survive quite well and can breed.  And, remarkably, the authors of the Cell paper report (again, if I understand correctly, and I think I do) that they were able to use a mouse EPS cell to give rise to a whole new mouse, not “just” a laboratory tissue hybrid.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.