Stem Cell Research and Technology

Summary

Stem cell research is the field of science that examines specific cells that can divide indefinitely in culture and give rise to specialized cells to provide therapy for diseases. There are two main types of stem cells—embryonic and somatic stem cells. Embryonic stem cells form in the early stages of embryonic development, and somatic stem cells are adult stem cells found in various tissues in the body. Stem cell research and technology have the potential to replace or repair a person's damaged or dysfunctional cells or tissues in treating or curing diseases.

Definition and Basic Principles

Stem cells have the basic properties of being undifferentiated cells that can divide indefinitely and have the potential to develop into many different types of cells in a body during early embryogenesis and growth of an individual. Stem cells are different from other cells in the body in that they can renew themselves through cell division, allowing them to act as a repair mechanism and replenish damaged or dead cells. When each stem cell divides, it has the potential to either remain a stem cell or become another cell type with a more specialized function.

There are two main types of stem cells—embryonic and somatic (also called adult stem cells). Embryonic stem cells are pluripotent—they can become any type of cell in the body. This is because these cells arise from the blastocyst early in embryogenesis, making up the inner mass of cells. The inner cell mass gives rise to the entire body of an organism, including all the specialized cell types and organs, such as the heart, muscle, brain, skin, and other tissues. Somatic stem cells are multipotent—they are found only in specialized tissues in the body, which are specific populations of cells used to generate replacements for cells that are damaged or dead because of normal aging, injury, or disease.

Stem cell therapy uses stem cells to replace or repair a patient's cells or tissues that are damaged or missing. Most stem cell therapy is still experimental in that it has not yet proven to be effective or safe, but stem cells have the potential to treat many diseases. The U.S. Food and Drug Administration (FDA) routinely reviews and approves stem cell therapies using blood stem cell transplants for patients with blood cancers or immune system diseases.

Background and History

Embryonic stem cells were first studied in mice in 1981 when scientists discovered ways to derive embryonic stem cells from mouse embryos. This led to the 1998 discovery of a method to derive stem cells from human embryos and grow them in the laboratory. However, the use of human embryonic stem cells—taken from embryos initially created for reproductive purposes—has been limited because several stem cell lines have been allowed to be grown in the laboratory for research purposes. This constraint led to further discoveries of how to derive stem cells from somatic tissues. In 2006, scientists discovered conditions allowing these specialized tissue stem cells to be reprogrammed genetically to become pluripotent. These stem cells, reprogrammed to express specific genes or maintain these cells in a stem cell-like state, are called induced pluripotent stem cells.

Stem cell research and technology remain the focus of much ethical, legal, and political debate, resulting in frequent policy and law changes. In March 2009, President Barack Obama lifted the ban on generating new stem cell lines, making federal funding for embryonic stem cell research available without the previous limits on the stem cell lines generated. Under President Donald Trump, fetal tissue research was limited, and an ethics panel was established to review grants. President Joe Biden reversed these policies in the early 2020s, allowing government scientists to resume research.

How It Works

To identify stem cells, cells must first be grown in the laboratory, or cultured. The first step in isolating stem cells is to transfer the inner cell mass of a blastocyst into a cultural medium in a laboratory dish. The culture medium contains nutrients that cells need to grow and divide. Stem cells do not always grow, but when they continue to grow and divide, they are then divided into other culture dishes, called subculturing, so millions of copies of the same stem cell (cloning) can be used for research.

Embryonic Stem Cells. Embryonic stem cells are the easiest stem cells to divide and reproduce in culture and have been shown to live for months without differentiating. When these cells continue in their stem cell state, they are considered pluripotent and have the same genetic makeup as the original stem cells from the inner cell mass. These cells are called an embryonic stem cell line. These cells may be frozen and shipped to other laboratories for further culturing and experimentation.

Somatic Stem Cells. Somatic (adult) stem cells are undifferentiated cells found in a tissue or organ that can renew themselves and differentiate to become specialized cells of that tissue or organ. Adult stem cells are used to regenerate or repair the tissue in which they are located. Known somatic stem cells are located in the brain, bone marrow, peripheral blood and blood vessels, muscles, skin, teeth, heart, liver, ovarian epithelium, and testes. To be used as a somatic stem cell, these cells need to demonstrate that they can generate a line of genetically identical cells that can give rise to all the differentiated cell types of that tissue. Once these cells are identified, they can be used to regenerate and repair cells within that tissue. Experiments are ongoing in transdifferentiation, in which certain somatic stem cells are reprogrammed into other cell types or even to become like embryonic stem cells, called induced pluripotent stem cells, with the introduction of embryonic cells.

Applications and Products

There are several reasons stem cells are important in science and the advancement of health care.

Cell Specialization and Development. Pluripotent stem cells help scientists understand the complexity of human development and how genes work to make decisions so that cells differentiate to become specialized cells. As development proceeds from an embryo to an individual human, genes turn on and off to give rise to protein expression and cell differentiation. These decision-making genes control the expression of pluripotent stem cells. Scientists know that certain diseases, such as cancer and birth defects, are caused by abnormal cell division and cell specialization. Understanding normal cell development will allow scientists to determine the errors that cause debilitating and often lethal diseases.

Medical Drug Testing. Stem cell research may change how medical drugs are developed and tested for safety. These new drugs can be tested on stem cell lines first. Using pluripotent stem lines will expand the cell types that can be tested in the laboratory before a drug is tested on animals and humans, streamlining drug development processes.

Cell Therapies. Stem cells have the potential to be used to generate cells and tissues that could replace or regenerate damaged cells and tissues in humans. Such cell therapies could help treat disorders that disrupt cell function or destroy tissues, such as cancer, heart disease, diabetes, spinal cord injury, arthritis, Parkinson's disease, and Alzheimer's disease. In 2011, the FDA approved the first hematopoietic progenitor cells-cord (HPC-C) cell therapy called Hemacord. Derived from umbilical cord blood, the treatment effectively treats leukemia, lymphoma, sickle cell anemia, and multiple sclerosis. Stem cells derived from bone marrow have shown efficacy in similar treatments and the preservation of bone marrow cells in patients undergoing radiation or chemotherapy.

Modern medicine relies on donated organs and tissues to replace destroyed tissue in heart, bone marrow, and kidney transplants. However, the number of people suffering from these disorders far outnumbers the organs and cells available. Stem cells offer a unique opportunity to create a renewable source of replacement cells and tissues to treat these diseases.

Another problem in the transplant process is that the recipient's body tends to reject the foreign cells from the donor. With stem cells, the research could focus on developing cell modifications to minimize tissue incompatibility or to create tissue banks with common tissue type profiles that many individuals would accept. Stem cells from human exfoliated deciduous teeth offer advantages over other stem cells as they can be easily isolated, regenerated into solid tissues, and used for donor’s close relatives.

Somatic Cell Nuclear Transfer. In somatic cell nuclear transfer, the nucleus of virtually any somatic cell is taken from an individual patient and fused with a donor egg cell from which the nucleus has been removed. That cell is then stimulated to develop into a blastocyst, and the inner cell mass is taken to create a culture of pluripotent stem cells. These stem cells can be stimulated to develop into specialized cells that are needed to repair damaged tissues or organs. Because the genetic information is taken from the individual patient, these cells theoretically would not be rejected by the patient as they are genetically identical to those of the individual. This type of transplantation would not require immune-suppressing drugs to be successful, and patients would have a far greater chance of survival.

Somatic Stem Cell Therapies. There are disadvantages and advantages to using somatic stem cells for therapies. One disadvantage is that these stem cells are multipotent but not pluripotent, and the types of cells that can be developed are limited. Previously, scientists believed somatic stem cells could develop into only the specialized cells from which they were derived, making it necessary to use only bone marrow stem cells for bone marrow transplantation, liver stem cells for liver diseases, and so on. However, experiments on mice have shown that various blood cell types were produced when neural stem cells were placed into bone marrow. So, even specialized stem cells may be manipulated to have a wider-reaching potential than previously thought. However, the biggest limitation of somatic stem cells is that they have yet to be isolated from all the tissues of the body.

Transplantation. One advantage of somatic stem cells is in transplantation. If these cells could be isolated from a patient and directed to divide and specialize in a manner that conveys normal cell function, they could then be transplanted back into the patient without immune rejection. This would also reduce or avoid the need for embryonic stem cells from human embryos or human fetal tissue. However, isolating somatic stem cells and growing them in culture has been difficult. Even if it becomes possible, growing and manipulating them quickly enough to correct a disease state may be impossible. Rigorous research will be required to overcome the obstacles of this type of cell therapy.

Multipotent hematopoietic stem cells (HSC) derived from bone marrow or blood can generate blood components, and their transplantation can help treat blood-related or hematopoietic problems like leukemia and thalassemia. However, such procedures still have limitations, like the requirement of antigen-matched donors and a low number of cells harvested.

Gene Therapy. Genetically modified stem cells or specialized cells derived from them can be used as vectors for delivering genetic material to replace mutated or missing genes. Research continues targeting specific areas for better treatment of gene disorders using a combination of gene therapy and stem cells.

Careers and Course Work

The field of stem cell research is growing, and careers in it can include medical doctors, doctorate-level researchers, and laboratory technologists with a bachelor's degree in biology or a related field. The number of laboratories conducting stem cell research is increasing, and funding for this type of research has expanded.

A bachelor's degree is required even for low-level positions in a research laboratory. A master's degree in a biological field may help in the competitive job market. A doctorate is essential to making decisions about the type of research and the funding received, as well as to direct a laboratory, including technologists. Medical doctors often participate in medical research at an institution and are involved in the patient aspect of the research and how it is applied in the clinical setting.

In the United States, the National Institutes of Health supports short-term training courses in human embryonic stem cell culture techniques. These training courses include hands-on experience to improve the knowledge and skills of biomedical researchers to maintain, characterize, and use human embryonic stem cells in basic research studies. The courses are given at various locations throughout the United States, including the University of North Carolina, Baylor College of Medicine in Texas, and Harvard University in Boston, Massachusetts.

Social Context and Future Prospects

Acceptance of stem cell research has been greatly expanded with publicity regarding the potential benefits of this type of research. Also, numerous scientific publications have led to advances in the field. However, considerable controversy remains regarding the ethical implications of using embryonic stem cells. In the United States, much debate has centered on the use of human embryos and fetal tissue created for reproductive use. Although these embryos are no longer needed, using them for research means they can no longer be used to produce a viable individual. The morals and ethics of this research remain a topic of debate.

However, stem cell research is not limited by the availability of embryonic stem cells. Alternative stem cells, such as somatic stem cells and induced stem cells, have been developed, and researchers may be able to use these instead. The competitive nature of scientific endeavors has led to the advancement of all fields of science, and continued work in this field has produced further success in the use and potential of stem cells to eliminate the threat of some of the most deadly human diseases. 

The use of these cells is continually expanding with research. In 2021, Singaporean research conducted the first-in-man clinical study for the scope of umbilical cord blood (UCB) cell therapy for treating hematopoietic disorders. The Harvard Stem Cell Institute conducts continuous research to uncover stem cell applications in treatment, diagnosis, and disease prevention. Applications uncovered in the 2020s range from life-saving to life-quality improvements—genetic engineering of pancreatic cells to treat Type 1 and rare genetic forms of diabetes, treating aggressive brain and spinal cord cancer called Glioblastomas (GBMs), understanding genes associated with autism spectrum disorder, the discovery of a new function of the protein alpha-synuclein which is a hallmark of Parkinson's disease, growing two layers of heart muscle cells from stem cells, and treating hearing loss with regenerative cells.

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