Tag: ips cells

Bioethics News

Pulmonary organoids produced from human iPS cells in three dimensions (3D)

Lung organoids have been produced from human pluripotent stem (iPS) cells that contain various components of lung tissue, and even airways and alveolar structures (see HERE). Recapitulation of lung development from human pluripotent stem cells (hPSCs) in three dimensions (3D) would allow deeper insight into human development, as well as the development of innovative strategies for disease modelling, drug discovery and regenerative medicine. Lung organoids produced resemble those of the second trimester of pregnancy. The authors discuss the potential use of this model to study pulmonary fibrosis in vitro and to model lung diseases.

Photo ARTICLES | Journal of Applied Physiology

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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.

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

  Rev Clin Esp. 2017 Jan – Feb;217(1):30-34. doi: 10.1016/j.rce.2016.08.003. Epub 2016 Oct 5.
Justo Aznar Ph.D. MD
Julio Tudela Pharm Ph.D.
Institute of Life Science – Bioethics Observatory
Catholic University of Valencia – Spai

iPS cells current clinical applications

Abstract

On the 10-year anniversary of the discovery of induced pluripotent stem – cells iPS cells, we review the main results from their various fields of application, the obstacles encountered during experimentation and the potential applications in clinical practice. The efficacy of induced pluripotent cells in clinical experimentation can be equated to that of human embryonic stem cells (see HERE); however, unlike stem cells, induced pluripotent cells do not involve the severe ethical difficulties entailed by the need to destroy human embryos to obtain them (see HERE). The finding of these cells, which was in its day a true scientific milestone worthy of a Nobel Prize in Medicine, is currently enveloped by light and shadow: high hopes for regenerative medicine versus the, as of yet, poorly controlled risks of unpredictable reactions, both in the processes of dedifferentiation and subsequent differentiation to the cell strains employed for therapeutic or experimentation goals (see more HERE).

KEYWORDS:

Cell reprogramming; Embryonic stem cells; Regenerative medicine; iPS cells

*Discovery of iPS cells, see HERE

*See HERE our article, Stem cell treatments with embryonic and iPS cells. Their usefulness (12-09-2016).

Photo: NATURE

 

La entrada Ten years since the discovery of iPS cells.

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.

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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.

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Intestinal tissue produced from embryonic stem cells and iPS

The intestinal nervous system controls several functions of the gastrointestinal tract, and when impaired causes bowel abnormalities. Now, a group of American researchers has generated intestinal tissue from embryonic and iPS cells (this last hasn’t ethics problems), using them to study the molecular basis of Hirschsprung disease. In the authors’ opinion, this is the first time that functional intestinal tissue has been produced that can be used to study motility disorders of the human gastrointestinal tract (See HERE).

Photo: University of Melbourne

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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.

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The situation of the clinical use of stem cells

In January 2017, an article was published in JAMA (The Promise of Palliative Care – Translating Clinical Trials to Clinical Care) which, in our opinion, summarises the situation of the clinical use of stem cells extremely well.

It begins by referring to the possible sources of stem cells: embryonic, adult and induced, the latter known as iPS cells.

Stem cells clinical use

It continues by saying that stem cells have many clinical applications, especially stem cells from bone marrow; these are used particularly in haematological diseases, but also in bone fractures, retinal diseases, spinal cord injuries, Parkinson’s and Huntington’s disease, and in myocardial infarction, although many of these treatments are still in the experimental phase.

While stem cells might sooner or later help to treat many patients, they can also have negative side effects if not used correctly, as these cells can emigrate to other parts of the body and create problems, as well as causing tumors.

Finally, the authors refer to the proliferation of clinics offering stem cell treatments, warning that many of these do not meet the necessary quality requirements, since they are not supervised by the health control agencies of the different countries and, as such, they offer the possibility of remarkable cures that are not yet medically proven. Cosmetic treatments and treatments for arthritis and autism are particularly sought after.

See our Special Report about this matter.

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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.

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Serotonin produced from neurons obtained with iPS and embryonic stem cells

Serotonin is implicated in functions as important as humour, sadness, feelings of aggression, anxiety and sleep disturbances, among others. A deficiency in serotonin release has been related with schizophrenia, depression, bipolar disorder, obsessive-compulsive disorders, chronic pain and eating disorders. All of this supports how important it is for the central nervous system to function well. Now, to facilitate “in-vitro” studies of the neurons that produce this substance, a technique has been developed that enables them to be obtained from human pluripotent cells, both embryonic and human iPS cells (Nature Biotechnology 34; 89-94, 2016). The use of human embryonic stem cells has objective ethical difficulties, but not so human iPS cells, so their use opens up a scientific and ethical avenue for the production this substance from neurons, and to take another step forward in the treatment of conditions linked to serotonin imbalance.

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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.

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Scientists closer to growing human organs in pigs

Scientists have moved closer to growing human organs in animals, with US researchers reporting that they have successfully created human-pig chimera embryos.

According to a study published this week in the journal Cell, geneticists from California’s Salk Institute have injected pig embryos with induced pluripotent stem cells (iPS cells) from humans, and then grown the embryos for a month. The iPS cells were injected in vitro into pig blastocysts, and the hybrid embryos were then returned to a sow for gestation.

The scientists said that after 28 days some of the iPS cells had developed into the precursors of various tissue types, including heart, liver and neurons.

Juan Carlos Izpisua Belmonte, who led the work on the part-pig, part-human embryos at the Salk Institute for Biological Studies in La Jolla, California, said: “The ultimate goal is to grow functional and transplantable tissue or organs, but we are far away from that. This is an important first step.”

The study raises a number of significant bioethics issues, including the risk of creating animals with human consciousness, and the dangers of accidentally introducing human-animal chimeras into the wild.

Dr David King, Director of Human Genetics Alert, the secular watchdog group, said:

“I find these experiments disturbing…The concern about mixing species touches something deep in the human psyche and our culture that is hard to put into words. It is not about some “wisdom of nature”, but about the unwisdom of scientists.’

Insoo Hyun, a medical ethicist at Case Western Reserve University, has no ethical objections to the experiments.

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 Therapy Has a Lot to Offer…It Just May Take Some Time to Get There

By: Ashwini Nagappan

In conversation with the New York Times, Dr. Shinya Yamanaka, the director of Kyoto University’s Center for iPS Cell Research and Application and researcher at the Gladstone Institutes, illuminates the complexities and future of stem-cell research. Yamanaka was jointly awarded the 2012 Nobel Prize in Physiology or Medicine for reconfiguring adult cells back to their pluripotent states. These induced pluripotent stem cells, or iPS cells, have been used as treatments for conditions such as macular degeneration.

However, Yamanaka mentions that these treatments are temporarily suspended because of the possibility of mutations developing in the patients’ iPS cells. Cancer could be a potential outcome because the production of iPS cells increases the chance of mutations. Researchers are rigorously testing to make sure that there are no cancer-causing mutations and that the cells function as they should. In order to be certain that these cells are safe, they are transplanted into mice or rats for about a year. Yamanaka approximates that only 100 lines would be needed to cover the Japanese population and 200 lines for the US population.

Yamanaka acknowledges that the potential for stem cells may have been too eagerly anticipated as they can only remedy the small portion of diseases that are caused by a single cell failure such as heart failure. Stem cell therapy cannot target diseases caused by multiple types of cell failures. He mentions an alternative to iPS known as direct cellular reprogramming, which would be beneficial if the patient in question was elderly instead of a younger person, and if the area targeted was larger instead of a small wound.

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.

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Ethical reflection on the latest biomedical experiments by Juan Carlos Izpisua and his group

Juan Carlos Izpisua biomedical experiments. They present serious ethical problems primarily because some of them use human embryonic stem cells

pdfOver the last few days, some of the biomedical experiments conducted by Juan Carlos Izpisua and his group — in which researchers from several Spanish universities take part — have been widely reported by various media.

Let us say at the outset that we see no need to highlight the biomedical importance of these experiments (some of which we would dare describe as spectacular), as this has already been abundantly emphasised by the media. Quite another matter is the possibility of being able to use what they have achieved in human medicine, which could take several years.

The bioethical aspects of these experiments have scarcely been addressed, however, and we believe they merit consideration.

Before we go any further, and in order to structure this report, the experiments by Izpisua to which we are referring should be divided into three groups. Concisely (although we will refer to this in more detail below) they are: a) to create quasi-human organs in animals, to be ultimately used for clinical transplants; b) to modify the CRISPR technique that offers so many biomedical possibilities, to make it more efficient, and c) to apply cell reprogramming “in vivo”, to try to rejuvenate a group of experimental animals.

  1. To create quasi-human organs in animals.

chimeraThese experiments were first reported in an article published in Nature in May 2015. They essentially consist in injecting human embryonic stem cells into mice so that they can generate quasi-human organs, since the human cells injected into the animal will produce organs with a genome that is very close to the human one.

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.