Stem Cells summary

We’ll all grow old and die one day. It’s inevitable. But along the way, wouldn’t it be ideal to avoid as many of the disabilities and diseases associated with old age as possible?

Medical conditions like Alzheimer’s disease or a stroke can be life-changing, and it’s only natural to hope for a “miracle cure” if you or a loved one are affected. But many claim that this miracle might already be here, in the form of stem cell therapy. As a result, a great deal of research – and a large sum of money – is now focused on this very area. But is it worth all the hype?

In this Blink to Jonathan Slack’s Stem Cells, we’ve kept medical jargon and technical aspects to a minimum. Instead, we focus on what stem cells are, the limitations of current stem cell treatments, and the potential for treatments in the future – all in an effort to get to the bottom of this complex science.

In this Blink, you’ll also discover

• why embryonic stem cells only exist in tissue cultures;
• what “the quickening” refers to; and
• the difference between pluripotent and tissue-specific stem cells.

As we’ve already mentioned, embryonic stem cells typically cause the most ethical and political debates – especially human ES cells.

Opponents of stem cell research often argue that preimplantation embryos should have full human rights and that using them to make ES cells is tantamount to murder. Usually, the reasoning is based on religious grounds. Modern-day Catholics, for instance, believe that human life begins at fertilization. Interestingly, this wasn't always the case. In the Middle Ages, the Catholic Church proclaimed that the soul entered the fetus during quickening. This was when a mother first felt the fetus move – around 18 to 24 weeks. Buddhists share the modern Catholic view, while Jewish and Islamic teachings acknowledge the embryo only after 40 days have passed. For Hindus, life starts depending on when reincarnation occurs – somewhere between conception and seven months.

Biomedical scientists’ views differ on many things. But they generally agree that personhood develops gradually and that preimplantation embryos aren’t human beings – they’re more like cell cultures or tissue samples. Martin Evans and Matthew Kaufman of Cambridge University, and Gail Martin of the University of California, first isolated mouse ES cells in 1981. The isolation of human ES cells followed about seven years later when James Thomson first grew them from human embryos at the University of Wisconsin. But, believe it or not, it’s actually mouse ES cells that have been the most important to science thus far.

These mouse cells can be injected into mouse blastocysts – an early-stage embryo which contains a clump of undifferentiated cells. They then integrate with the host embryo, and the resulting offspring carry the gene variants injected at the blastocyst stage. The result? A line of genetically modified mice.

Big deal, huh? Well, yes, actually! The last 35 years of research on tens of thousands of genetically modified mice has been based on this very technique. Without these mice, a lot of the research on human diseases, investigations into normal gene function, and testing of new drugs wouldn’t have been possible.

Human ES cells share many of the same properties as those of mouse ES cells, including being made from embryos. But there are some big differences.

For example, we now know there are two pluripotent cell states known as naive and primed. Mouse ES cells are the naive type, and human ES cells are primed. Scientists don’t yet know why this is the case, but it results in differences in gene expression, appearance, and behavior. Only naive cells can be integrated into a host embryo, whereas only primed cells can carry out the process of differentiation.

So, where do human ES cells come into the picture? Well, scientists use them in three main areas of research – normal human development, the cellular pathology of genetic diseases, and drug screening – which may remove the need for animal testing.

It’s 1997 and Ian Wilmut is working at the Roslin Institute near Edinburgh, Scotland. He takes the nucleus from a sheep tissue culture cell and transplants it into the enucleated oocyte of a female sheep. He then transfers the resulting embryo into the uterus of another sheep, which acts as a surrogate mother. Some 22 weeks later, a newborn lamb becomes the first-ever cloned mammal: Dolly.

Actually, successful cloning had been around long before Dolly. By the late nineteenth century, scientists had managed to clone frogs and sea urchins.

Cloning something means making an identical genetic copy. These days, it’s a common enough procedure and occurs virtually every day around the world in every biomedical laboratory. But the type of cloning we’re talking about here isn’t as dramatic as cloning a full animal – it’s growing a colony of cells, where each cell is genetically identical to its founder.

Most people agree that cloning humans would be a bad idea. But by using somatic cell nuclear transplantation – the process used in producing the embryo that went on to become Dolly – it’s possible to establish an ES cell line as a source for therapeutic cloning.

It’s not easy to do. First achieved in 2013, it’s only been successfully repeated in a few labs. Part of the problem is obtaining human oocytes, which have to be surgically harvested from human female volunteers – an unpleasant and risky procedure. Then, only a small minority of reconstituted eggs successfully develop into an ES cell line.

In 2006, Shinya Yamanaka of Kyoto University discovered a new methodology that made it easier to produce cells similar to ES cells, called induced pluripotent stem – or iPS – cells. One year later, human iPS cells were being made. Nowadays, they can be produced using white blood cells extracted from a simple blood sample.

iPS cells are patient-specific. As such, differentiated cells are an immunological match to the donor. This means that if these cells are grafted back to the patient, there’s no need for immunosuppressive drugs. At present, though, the costs of production are too high for this treatment to be viable.

Instead, banks of iPS cell lines are being created in the hope that most of the population could find a suitable match for grafting and only require a minimal amount of immunosuppression. Research into other solutions is also underway. 

Of all the therapies, the treatment of retinal degeneration has had the most success – and promise for the future. Roughly 10 percent of people over the age of 65 experience a degree of age-related macular degeneration, or ARMD, in the center of the eye’s retina. Severe cases are characterized by a loss of central vision, which results in an inability to read and to recognize faces. Clinical trials carried out in several countries since 2011 have shown that grafts below the retina have few side effects and require little immunosuppression. Most treatments have resulted in an improvement in visual acuity. A high prevalence of ARMD coupled with a relatively simple treatment means that it’s likely this will be used more frequently in the future.

Similar types of pluripotent cell therapies are also in the works to treat type 1 diabetes, Parkinson’s disease, heart disease, and even spinal injuries – but, so far, studies show varying results.

Our bodies are continually exchanging cells: cells die, and new cells replace them. But not all cells do this in the same way.

Some cells, known as post-mitotic cells, don’t ever divide again. Examples of these are neurons and muscle fibers. 

Other cells, known as expanding cells, divide only during our childhood; they stop when we stop growing. These include cells in connective tissues and in many organs, including the liver, kidneys, thyroid, and others.

And then there are others, known as renewal cells, that continually replace the tissues in which they’re found; they generate new cells exactly in time with the death of old cells. Renewal cells persist for the whole life of the organism. In humans, they’re found in the epidermis, as well as in things like our intestines, testicles, and the hematopoietic system of our bone marrow – which is responsible for generating both blood cells and the cells of our immune system. 

Over 50,000 hematopoietic stem cell transplants – HSCTs – are performed around the world annually. It’s undoubtedly the most important type of stem cell therapy currently in use. Better known as “bone marrow transplantation,” HSCT is now the preferred term as it also covers transplants where the blood-forming cells come from other sources, like the umbilical cord. Its main use is to treat leukemia and lymphoma. HSCT has also been used to treat some genetic blood diseases, including sickle cell anemia and a group of hemoglobin diseases.

Other existing treatments rely on tissue-specific stem cells. For instance, it’s possible to use cultured epidermis to treat severe burns, or to use stem cells from the cornea to treat eye diseases and injuries.

We can all be thankful for the advances in medicine in the twentieth and twenty-first centuries. Yet future generations may look back on us with disbelief: we live in a time where spinal injuries can lead to full paralysis, where lost limbs can't be regenerated, and where heart failure and cancer can end in death.

The hype surrounding the promise of cures in the 2000s was partly a result of the controversies over human embryonic stem cells. Many politicians also believed stem cell therapy would be “the next big thing” that might rescue them from failing economies. But scientists are less optimistic about therapies; they see more value in research on embryonic development and in drug screening.

When we think about the future, we can draw some lessons from hematopoietic stem cell transplantation, or HSCT – a story that analysts wouldn’t have been able to predict in advance.

First of all, little was known about the hematopoietic system in the 1950s when research in this field began. It took decades before hematopoietic stem cells were finally isolated in mice in 1988 – and then a few more years before they were isolated in humans. 

In spite of advances in cure rates for diseases like leukemia, the treatment is very aggressive and there’s a high mortality rate. This means it’s not suited to treat many other diseases where the risks can’t be justified. Plus, the cost of HSCT treatment is prohibitively expensive – upward of $600,000 in the US and €200,000 in Germany. 

Looking back at all this with the benefit of hindsight, we can see that knowledge of the hematopoietic system was only acquired as a result of the research. Many of the discoveries had no potential commercial value. And others that did were discarded during development. There have been long delays between understanding the biology and the implementation of new therapies. In the case of HSCT, it took around 20 years. Regulations today would probably make that much longer.

Gene and cell manipulation will yield great innovations in the future. In the next ten years alone, there’ll probably be some advances in stem cell therapy: cell grafts may be able to treat age-related macular degeneration in the eyes, dopaminergic neurons for Parkinson’s disease, and cardiomyocytes to repair damaged hearts. Treatment of type 1 diabetes through implants of pancreatic beta cells may also prove feasible. And we may even see the reversal of paralysis from spinal trauma.

Stem cell biology has enormous potential. But predicting its future is difficult. Biomedical scientists believe that we’ll someday be able to regenerate missing limbs, and there’ll certainly be cures for diabetes, cancer, and heart failure. But progress toward these outcomes will likely be slow – and require a lot more research.