Stem Cells

Discovering the Potential

The scientific study of stem cells has existed for a long time and has already contributed greatly to modern medicine. As scientific inquiry continues to advance and as discoveries gain more traction and acceptance in the scientific and medical communities, the true breadth and potential of this area of study can start to be realized.
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Though it remains a controversial area of study for some, for others, stem cells show great promise. If scientists can differentiate adult stem cells in a controlled environment, stem cell therapies could revolutionize modern medicine.

Discovered in the 1950s and first transplanted in the late 1960s, adult haematopoietic stem cells from bone marrow were the first instance of stem cell therapy and there is hope that with new discoveries and advancements in the field, greater medical benefits and applications will arise. Until recently, very little was known about stem cells and their potential uses, but research is yielding promising results.

Stem cells are defined as: “An undifferentiated cell of a multicellular organism which is capable of giving rise to indefinitely more cells of the same type, and from which certain other kinds of cell arise by differentiation,” by Oxford Dictionary; this only begins to scratch the surface of the complex composition and untapped potential of stem cells.

Scientists want to understand how stem cells have the potential to develop into different types of cells in the human body as it grows. Stem cells are unique, in that they can divide and multiply, replenishing and repairing other cells in the body. The unique aspect is that stem cells can remain as a stem cell or can develop into a different kind of cell that is more specialized in its function.

Stem cells vary from other cells in two ways: they are unspecialized and are capable of multiplication through division, dependent on the environment and circumstances to which they are subject. Through a process of differentiation, they can become tissue- and organ-specific specialized cells.

All stem cells share three general properties: they can divide and regenerate many times, called proliferating; they are unspecialized, meaning they do not have tissue-specific structures that make them specialized; and they also have the capacity to become specialized cells. This occurs through a process of differentiation and takes place in stages.

For years, scientists believed that only two kinds of stem cell existed: embryonic stem cells and non-embryonic stem cells, otherwise referred to as adult or somatic stem cells. Embryonic stem cells have traditionally been derived from animals.

Scientists first discovered embryonic stem cells in mice in 1981, leading to a whole new world of discovery. In 1988, the first embryonic stem cells were developed from hamsters while the first embryonic stem cell lines from a primate didn’t occur until 1995. And everyone knows about the successfully cloned lamb named Dolly in 1996.

The following year, scientists discovered the origins of leukaemia were in the haematopoietic stem cells. This was significant for those working toward a cancer cure as it was the first instance of a cancer-related stem cell. The 1990s was also when scientists first discovered the existence of stem cells in the adult brain.

In 1998, scientists investigated human embryonic stem cells that were no longer being used for in vitro fertilization. The existence of different stem cell types did a lot for the study of proliferation and differentiation of stem cells, especially human embryonic stem cells. The ability to grow embryonic stem cells without using mice or other non-human sources eliminates a great deal of risk related to the transmission of viruses from the animal to human cells. This was a terrific advancement for science that was very promising for stem cell-based therapies.

A major discovery took place in 2006 when scientists identified conditions in which some specialized mouse-derived adult stem cells could be differentiated through genetic modification to create a new type of cell known as induced pluripotent stem cells (IPSC). Human IPSCs were discovered a year later.

A great deal of effort has been dedicated to establishing a standard process to grow and test the cells’ properties. This is necessary to determine whether stem cells can be sub-cultured, to determine the cells’ ability to re-grow after they have been frozen and stored, and what actions must be taken to ensure their successful re-plating and growth. Scientists have discovered that embryonic stem cell cultures will grow if the ideal conditions exist and can remain undifferentiated in this environment. If they clump, that is a sign that the process of differentiation could occur and that the culture is healthy, though the process remains uncontrolled.

To create specialized, differentiated cells that serve a specific medical purpose, i.e. blood cells, scientists need a way to control the process of differentiation. If this is achieved, treatments for a variety of medical conditions such as diabetes, spinal cord injuries, multiple sclerosis, muscular dystrophy, Alzheimer’s, and even heart disease and arthritis could be discovered.

Unlike embryonic stem cells, adult stem cells are undifferentiated cells that are found in tissues and organs in the body, such as the brain, bone marrow, blood, teeth, skin, heart, liver, and many other vital organs. These cells can differentiate to become specialized cells and support repair and regeneration efforts in the tissue or organ of which they are a part. Scientists are discovering an increasing number of sources of origin of these cells – new tissues and organs that contain adult stem cells.

Scientists know that adult stem cells can occur in multiple tissues in the body, entering normal differentiation pathways to achieve specialization. There are many examples of different pathways where adult stem cells can enter in the many tissues in which they can exist, dividing over a long period to become specialized: mesenchymal stem cells, neural stem cells, and epithelial stem cells, for example.

Embryonic stem cells are pluripotent, meaning they have the capacity to become any specialized cell in the body through differentiation, making cultures easier to grow; adult stem cells are limited in this regard. Similarly, adult stem cells are rarer and more difficult to extract and culture, though they are more likely to be successfully transplanted and less likely to be rejected by a patient’s immune system.

Human stem cells can provide insight into human development – chiefly, how undifferentiated cells become specialized through differentiation. Scientists can study the genes and their impact on development, focussing on abnormal developments such as cancer and environmental influences. Indeed, internal and external conditions influence the differentiation of stem cells. Scientists are still working diligently to understand how proliferation and self-renewal occurs and what environmental conditions can help to encourage and regulate this process to achieve desired results.

For example, cancer is thought to occur because of problems in the differentiation process. By understanding how normal cells divide and multiply, cell abnormalities can also be better understood which could lead to better treatments and perhaps even preventative measures to avert these abnormalities.

Another potential application is the ability to address the demand for transplantable tissues and organs, as stem cells could serve as a renewable resource in this capacity. Substantial headway has been made in the area of stem cell research dedicated to the treatment and reversal of cardiovascular disease and diabetes.

It has been discovered that stem cells are capable of something called transdifferentiation. Transdifferentiation has been identified in several species, though it remains to be seen in human stem cells. In human cells, scientists have had to fuse a donor cell, or transplant a stem cell to achieve human stem cell division and multiplication – essentially reprogramming cells through genetic modification.

Currently, stem cells are being used to test new drugs. IPSCs show great application in this area, as it would allow for drug testing on a wider variety of cell types. Regardless of the potential and how far scientific discovery has come, many questions still require answering: How many kinds of cells exist? How do they evolve and exist? What are their core characteristics in various environments? Several technical hurdles must be overcome, such as discovering how to proliferate large quantities of cells, enough to be impactful, as well as understanding how to differentiate these cells into the desired specialized cell type.

Further to these hurdles, there is still concern related to the implantation and acceptance of the new tissue and its ability to function as intended in the patient going forward. These hurdles are being overcome, one by one, as scientific inquiry advances.

The area of study related to stems cells has offered a new source of hope for many people. In December, 2016, scientists from Tomsk Polytechnic University’s Laboratory of Novel Dosage developed a technology to use mesenchymal stem cells to help fight cancer cells in the body.

As the field of study continues to advance, ethical issues and regulatory frameworks must be considered. Discourse has taken place in the political, public, and religious spheres to establish laws and regulations related to stem cell harvesting and scientific study related to stem cells. The goal is to ensure ethical research that will support advancements.

In 2016, the International Society for Stem Cell Research (ISSCR), which endorses ethical and evidence-based research that could result in the advancement of prevention and treatment of disease, were consulted by the Australian Therapeutic Goods Administration regarding the regulation of autologous cell and tissues and the ISSCR responded.

The ISSCR endorses the regulation of autologous products that “involve more than minimal manipulation of a patient’s cells and place strict limitations on the direct advertisement of cell-based therapies,” the highest level of regulatory oversight scheme made available during consultation, highlighting the importance of “proactive regulatory oversight” in the interest of public safety.

Be they controversial, stem cells have great potential, and as scientific discovery advances, the greater the potential grows. Once science can more concretely identify and understand stem cells, their characteristics, and their uses, greater public benefit will result. Change is always fraught with uncertainty, but sometimes the greatest changes come from the most controversial moments.

For those who are currently suffering from a serious life-threatening or debilitating disease, stem cell therapies cannot come soon enough. The potential for the therapies, treatments, and cures that the scientific and medical communities are excited about could very well become a reality.

The regulatory environment is one which supports further study in hopes of advancement. Research continues to break ground, as these studies are receiving a great deal of support and funding. As more details emerge related to the unique and complex characteristics of stem cells and their differentiation and proliferation, greater medical advancements can continue to be made.

Stem Cells

The scientific study of stem cells has existed for a long time and has already contributed greatly to modern medicine. As scientific inquiry continues to advance and as discoveries gain more traction and acceptance in the scientific and medical communities, the true breadth and potential of this area of study can start to be realized.

September 20, 2017, 7:06 PM AEST

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