The development of the atomic bomb during World War II brought unprecedented devastation to the Japanese cities of Hiroshima and Nagasaki. However, this tragedy also stimulated a wave of biomedical research aimed at both understanding the effects of radiation and developing treatments for radiation exposure. This research ultimately led to the development of the bone marrow transplant, which has saved countless lives and is the only broadly available stem cell therapy in use today .
One of the major breakthroughs for bone marrow transplants came in the 1950s, six years after the bombs were dropped on Hiroshima and Nagasaki. At this time, Egon Lorentz showed that mice could recover from a lethal dose of radiation if they received bone marrow from a healthy donor . When doctors transplant bone marrow into a patient, hematopoietic stem cells (HSCs) naturally present in the bone marrow are transferred from donor to recipient. HSCs have the unique ability to become any kind of cell in the blood, so donor HSCs grow and divide to replace all types of blood cells in the recipient. These include red blood cells that carry oxygen through the body as well as other cells critical to immune function. Moreover, because stem cells by definition generate additional stem cells, bone marrow transplants continue to supply healthy blood cells over time. This makes bone marrow transplants a powerful clinical tool, and to this day, a similar approach is used to treat leukemia. Chemotherapy or radiation designed to kill cancer cells is often followed by hematopoietic stem cell transplant in order to promote growth of a new, healthy blood supply .
It may come as a surprise that bone marrow transplants constitute a form of stem cell therapy. That is because most people use “stem cells” to refer to embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) when they discuss this topic. (For a more detailed description of ESCs and iPSCS, see Stem Cells: A Brief History and Outlook.) By contrast, bone marrow transplants take advantage of a population of adult HSCs, which can only become blood cells. This is what distinguishes them from ESCs and iPSCs, which are capable of developing into a much broader range of cell types. As a consequence, the utility of hematopoietic stem cells is limited mainly to diseases that occur or originate in the blood or bone marrow.
Scientists are now working to establish other forms of stem cell therapies, but none are as well established as the bone marrow transplant. Here, we will discuss one example of a stem cell therapy currently in development. We will then touch on the major technical challenges that have slowed the creation of new stem cell therapeutics.
The Promise of Vision: A Case Study
As with any potential medical treatment, stem cell therapies must go through a rigorous set of experiments and clinical trials before they can be approved for widespread use. So far, the most successful trials have used human embryonic stem cells (hESCs) to treat patients with Stargardt’s Macular Dystrophy and age-related macular degeneration [3, 4]. These diseases affect a specific layer of cells in the eye known as the retinal pigmented epithelium (RPE). Because the RPE performs several functions that are critical for the detection and processing of light, patients eventually lose their eyesight and become blind .
Figure 1: Outline of a stem cell treatment for Stargardt’s Macular Dystrophy and age-related macular degeneration. Scientists first isolate human embryonic stem cells, then provide the environmental conditions necessary for these cells to become retinal pigmented epithelium (RPE) cells. These RPE cells are then transplanted into a patient’s eye to allow new cells to replace the RPE cells lost due to disease. Figure created by Hannah Somhegyi.
To test the utility of stem cell therapy for the treatment of Stargardt’s Macular Dystrophy and age-related macular degeneration, scientists chose patients who had already lost the majority of their vision. A group of doctors and scientists then grew stem cells in a dish . By providing a particular combination of proteins and nutrients, they made the stem cells lose their “stem-like” properties and become mature RPE cells. Doctors then transplanted RPE cells to a specific region of the eye (see Figure 1). The results showed great promise. Transplanted cells appeared to survive, grow, and associate with other cells in the correct region of the eye. Moreover, patients did not show signs of negative side effects, and tests suggested that vision actually improved. This is not to say that patients regained their sight; rather, it suggests that the treatment shows potential. For example, a patient who could only see hand motions prior to surgery was able to count fingers after the transplant. This improvement may seem minimal, but the benefits of treatment could be more pronounced if transplants were given prior to profound loss of vision. Nevertheless, additional clinical trials will have to take place before the treatment can be made more readily available.
Barriers to Progress: The Challenges of Stem Cell Biology
Stem cells could in theory be used to treat any number of diseases. You might therefore wonder why progress has been so slow, given that the first successful bone marrow transplant took place over fifty years ago. The answer is not trivial. To begin with, hematopoietic stem cells (HSCs) present in the bone marrow are a unique example of adult stem cells that can be easily accessed for clinical or research purposes. Though other adult stem cells do exist, they can only form a limited number of cell types (just as hematopoietic stem cells can only form blood cells), and most are far more difficult to access. For example, populations of adult neuronal stem cells are present deep within the brain, but removing these cells would require penetrating the skull and brain tissue. Thus, researchers have focused much of their efforts on using the more versatile ESCs and iPSCs for the development of therapeutics.
In order to actually use ESCs and iPSCs, scientists have to develop stem cell lines. This means that scientists must put stem cells in a dish and grow them in an environment that allows the cells to retain their unique, “stem-like” properties. This alone was a major roadblock in the field of stem cell biology. Indeed, the first line of human-derived ESCs was not created until 1998, and iPSC lines did not even exist until 2006.  When you consider this timeline, the development of ESC- and iPSC-based stem cell therapies does not seem slow at all.
Stem cell therapies also present technical challenges that must be addressed for safety. Because of their ability to produce a large number of cells, ESCs and iPSCs can generate tumors in the body. Thus, therapies require that scientists direct the growth of these cells into the specific cell type needed to treat a given disease. However, discovering and replicating the precise environmental conditions needed to make stem cells become the desired cell type can be an arduous process. Further, much like organ transplants, transplantation of stem cells presents the possibility of immune rejection. Patients must be matched with an appropriate stem cell line, or iPSCs must be developed from individual patients to prevent immune rejection (indeed, this is one of the benefits of iPSCs). Of course, these are only some of the technical concerns associated with stem cell therapeutic advancement.
Conclusion: A Promising Future
The success of early clinical trials for ESC-based therapeutics in diseases of the eye brings with it great hope for the future of stem cell therapy. Indeed, new trials are emerging for the treatment of diseases like Parkinson’s Disease . It would, however, be wrong to suggest that all stem cell therapies have met with success. Several trials have been terminated early (treatment of spinal cord injury ) or have shown limited medical benefits (treatment of Amyotrophic Lateral Sclerosis). Nevertheless, biomedical research is constantly evolving, and more expanded options for stem cell therapy may emerge not too far into the future.
Elizabeth Lamkin is a graduate student in the Program in Neuroscience at Harvard University.
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3 thoughts on “Hope Amidst Tragedy: Stem Cell Therapies and the Atomic Bomb”
please I’ll like to have private discuss with the author concerning the subject of discourse most especially on the issue of the status of the embryo. one is the embryo a human person? does the embryo deserves or shares same rights and protection as with full human adult or person or is their any violation in the process of using the embryo for research purpose?
Hello and thanks for reading! Legally, an embryo from which ESCs are derived is not considered a human person (usually it’s from a pre-implantation embryo from IVF clinics). You can read more about ESCs and how they are grown in the lab here: https://stemcells.nih.gov/info/basics/3.htm
Stem-cell therapy is widely defined as the use of stem cells for treating or preventing a disease or condition. The most widely used stem cell therapy today is via bone marrow transplant, but with the exponential growth of technology and medical research, therapies derived from umbilical cord blood are growing in popularity. For more details please visit here: https://www.cordlifeindia.com/about-stem-cells