The realities, ethical dilemmas and medical promises of an emerging field of research.
The news about stem cell treatments never ceases to surprise. Without a doubt, these generic cells, capable of generating all the different types of cells that exist in an organism, are the biological treasure of the 21st century. Fully understanding how it works occupies the minds and resources of thousands of scientists around the world, and for good reason. Tools are expected from stem cells to treat health problems ranging from skin burns to cornea, kidney and liver transplants. The media hails them as salvation from blindness, baldness and wrinkles; or they present them as a future solution for diseases such as type 1 diabetes, Alzheimer’s disease and Parkinson’s disease. Although it seems exaggerated, the results reported each year allow us to dream that the future is practically just around the corner.
wonders in sight
In 2014, three people with spinal cord injuries received injections of stem cells derived from embryonic nervous tissue at Balgrist University Hospital in Zurich, Switzerland. Six months after treatment, two of the patients could already feel stimuli such as pressure, cold, heat and electrical touches on their skin. By 2015, two more people had reported the same improvements. Although the news provided hopeful results for people with paralysis, the road ahead is still very long: the treatment gave patients back sensation in their skin, but it did not improve the body’s function. Spinal cord injuries involve a host of factors beyond just a few damaged cells. Furthermore, each injury is different, and according to its characteristics, the environment in which the cells live drastically changes (toxins are released into the bloodstream, scars are generated that make movement impossible, etc.). Stem cell injections to treat paralysis are a good start, but scientists still need to fully understand the mechanisms that promote improvements. Without this understanding, effective large-scale treatments cannot be considered, and for the moment the research remains in the clinical study phase. However, despite the flaws and blanks, stem cells are the possible solution for many diseases and illnesses.
The medical promise of stem cell treatments is beginning to crystallize and its findings seem to come from science fiction. While a team develops skin extensions in a Petri dish to replace damaged segments in patients who suffered severe burns, Harald C. Ott of Massachusetts General Hospital looks closely at the first rat kidney designed and built in a laboratory at from a handful of cells carefully fed in a glass box, and is excited when he discovers that the organ is capable of filtering urine. Subsequent transplantation of the kidney into a live rat will demonstrate whether the organ functions both in the laboratory and in a living system. At the same time, Mark Post, from Maastricht University, the Netherlands, presents to the world the first meat burger generated in a laboratory from cow stem cells. It is a time of realities combined with wonders.
Origin does matter
One cannot talk about stem cells without considering the ethical dilemma that constantly accompanies the topic, and this boils down to this question: where do the cells used in research or treatment come from? At first, the source of stem cells by definition was the blastocyst, an early stage of the embryo that forms a few days after fertilization. The approximately 200 cells of the blastocyst are very special, as they can generate all the cells in the body. Because they are capable of generating cells of any type, embryonic stem cells are considered pluripotential. To obtain them, the blastocyst must be destroyed, which is why research with pluripotent stem cells is subject to a tight scheme of ethical guidelines and constant worldwide surveillance.
Fortunately, in the last two decades, reserves of stem cells have been discovered in the adult organism, which could make it possible to overcome the problem of obtaining them from embryos. The disadvantage is that adult stem cells are few and are not as flexible or durable as embryonic stem cells.
Stem cells are found in the spinal cord, tooth pulp, retina, blood, placenta and umbilical cord, to name a few sources. Dr. Mayana Zatz, from the University of Sao Paulo, Brazil, comments with good humor that her research on muscular dystrophy with stem cells will benefit from many donors now that her team has obtained stem cells from adipose tissue which is removed during liposuction. These fat-derived cells have been used in the laboratory to produce dystrophin, a protein essential for muscle function that is no longer produced in the cells of people with muscular dystrophy. The procedure has worked in rodents and dogs with this condition, so clinical trials with humans are expected in the coming years.
Suddenly, even in small quantities, non-embryonic stem cells are even in the fat! The natural function of these cells is to divide to produce cells of specific types to regenerate the tissues around them. Within the body, these cells only give rise to certain types of cells, which is why they are called multipotential: hematopoietic stem cells, for example, constantly replenish platelets, white blood cells and red blood cells, but are unable to generate cardiac cells, muscle cells or neurons. Although not as flexible as pluripotent cells, these cells are a fantastic source for stem cell research.
Back to the Future
In 2006, Japanese doctor Shinya Yamanaka made a discovery that revolutionized our understanding of cellular physiology. Yamanaka, a doctor specializing in severe spinal cord injuries, joined the numerous groups of scientists already investigating the functioning of stem cells at the University of Tokyo. But Yamanaka brought a different perspective: while other groups attempted to direct a stem cell toward the cell type that was required (i.e., direct the process “forward”), Yamanaka was more interested in understanding the specialized cell process by following the reverse tracks to the origin. The researcher wondered why stem cells scattered here and there in the adult body could remain in that state instead of suffering the same fate as their neighbors and transforming into more specialized cells. In other words, he was interested in finding the essence of pluripotentiality. Stem cells have the ability to produce cells that will behave like them, will not undergo any specialization and will continue to produce stem cells in a process of constant renewal of this valuable biological reserve. But they can also give rise to daughter cells that follow other paths and respond to signals from the environment to become blood cells, neurons, liver cells, heart cells, muscle cells and all types.
In the words of Austin Smith of the University of Cambridge, Yamanaka was attracted by the moment in which the stem cell “has to make a decision: give rise to daughter cells that in turn act as stem cells, or give rise to cells daughters that continue physiological processes of differentiation until they become specialized cells. In an interview, Yamanaka narrates that his research started from considering that in the same person, a pluripotent cell and a skin cell contain the same genetic information. What makes them so different in function and form is that the same DNA segments are not active.
Yamanaka assumed that if he managed to introduce into the skin cell the biochemical factors that give instructions to stop the differentiation process, this already differentiated mature cell could be reprogrammed to reverse its specialization; That is, making it go back in time so that it behaves like a stem cell again. Yamanaka began by identifying the factors capable of promoting cellular reprogramming. Initially, the researcher and his team considered a hundred proteins that could act together or separately. This gave rise to more than a million combinations, but the final answer was surprisingly simple: it was enough to add, using a retrovirus, four factors to the culture of skin cells to obtain cellular reprogramming. These factors, called Sox2, Oct4, c-Myc and Klf4, act at the same time in embryonic stem cells and together constitute the essence of pluripotency. Yamanaka named the resulting stem cells induced pluripotent stem cells (iPS). His discovery opened the possibility of doing research with stem cells that do not come from embryos. Currently, iPS are grown on a large scale in laboratories around the world. For this discovery Shinya Yamanaka received the Nobel Prize in Physiology or Medicine in 2012.
The fall of Icarus
The promises of stem cells have dazzled more than one in the same way that the mythical Icarus was dazzled by the beauty of the Sun and lost his wax wings for getting too close. This has led to some scandals. One of the most famous cases is that of the South Korean scientist Hwang Woo-suk. This researcher appeared in the most important media in the world during 2004 and 2005, when he announced findings related to the creation of pluripotent cell lines obtained from the nuclei of mature cells, among other findings. Magazine Science published his articles, in which several apparently perfect and magnificent cell lines for research were seen, but soon several scientists from various parts of the world began to detect flaws in the images and methodology. The scandal grew in 2006, when it was discovered that Woo-suk had forced several of his students to “donate” biological material for research. Woo-suk was even on the verge of going to jail.
The most recent scandal occurred in 2014, when researcher Haruko Obokata, from the Riken Center, in Kobe, Japan, published in the journal Nature an amazingly simple methodology to generate stem cells from baths with acidic agents in 30 minutes! The procedure, known as STAP, was…