Joanne P. Shelby-Klein, BSN, RN

Stem Cells, all human beings and animals have them, but what are they and what can they do?

Stem Cells are the forerunners or building blocks of all cells in the human body. They are able to reproduce themselves to replace or fix the different tissues in the body. All cells in the human body are unique and have specific unchanging duties. These include, skin cells, muscle cells, any and all cells human beings have. Stem Cells, unlike fully formed cells, have not grown into their specific identity and function. Stem Cells can renew themselves by cell division even after being inactive for a long time. Under either natural physical or controlled laboratory conditions, they can be adjusted to become a specific tissue or organ cell and perform various jobs. Some organs, especially in the abdomen and bone marrow, have stem cells that regularly become active to repair damaged tissues. Stem cells have a huge potential to offer new treatments for many diseases. In fact, scientists are already using stem cells to look at normal growth and development, as well as birth defects and screening for medications.

Scientists have been working with two types of stem cells from both animals and humans. One cell type is the Embryonic Stem Cell (ESC), the other is Somatic or Adult Stem Cells. Both types of stem cells have the following in common: they can divide and renew for extended periods of time, they have no special functions and can give birth to special cell types as needed. Unlike blood cells, muscle tissue or nerve cells, stem cells can increase in numbers many times over. if they remain an unspecialized cell, they are considered to be capable of long term self renewal. How and why this occurs is of great interest to scientists. They need to understand why some cells remain and can grow to numbers, in order to continue researching stem cell use in medicine. The ongoing research will continue to answer questions about how an organism grows and replaces damaged cells in the body.

EMBRYONIC STEM CELLS (ESC)

Embryonic stem cells come from embryos, usually developed from eggs that have been fertilized in a clinic and given for research, not from fertilized eggs in a womans body. The process of growing eggs in the lab is known as a cell culture. Embryonic stem cells are started by putting cells not yet implanted in the uterus onto a plastic lab culture dish that contains a special culture broth. The culture broth causes the cells to divide and spread across the dish. Cells that divide and spread enough will have samples taken and put into another culture dish. This process is repeated many times over many months and produce millions of cells. Embryonic stem cells that grow in the culture dish without changing to a specific type of cell are called the stem cell line.

ADULT STEM CELLS

It is believed that an adult stem cell is a cell that has no specific duty and is found between specialized cells in a tissue or organ. Adult stem cells can renew and regenerate to become part of some or all of the special cells of a tissue or organ. The main responsibility of adult stem cells is to maintain and fix the tissue in which they are found. Scientists may refer to adult stem cells as Somatic stem cells. Somatic refers to the cells of the body that are mature.

Research on adult stem cells has been going on since the 1950’s and generates interest and excitement. Adult stem cells have been found in more tissues than scientists thought possible. Researchers and doctors have been asking if adult stem cells could be used for transplant. Adult blood forming stem cells found in the bone marrow have been used for transplantation for over 40 years. There is now evidence that stem cells exist in the brain and heart, areas where they were not expected to exist. This offers hope that if the specialization of stem cells can be carefully controlled in the lab, new transplantation based therapies can be developed.

Adult stem cells have been found in many organs and tissues such as the brain, bone marrow, blood, blood vessels, muscles, skin, teeth, heart, liver, abdomen, ovaries and testis. It is believed that stem cells may remain dormant until they are called into action to make more cells to maintain tissues or because of an injury/disease.

Making quantities of stem cells is difficult. Many scientists are working to grow quantities in a culture dish and stimulate growth into specific cell types. Scientists are working on treatments for regenerating bone, making insulin producing cells for diabetes type-1 treatment and repairing heart muscle damage. Research in this and other disease processes is ongoing.

Adult stem cells come in different specialized types depending on where they are found in the body.

• Hematopoetic stem cells help form all types of blood cells including red blood cells, white blood cells, B lymphocytes, T lymphocytes, natural killer cells, neutrophils, basophils, eosinophils, monocytes and macrophages.

• Mesenchymal stem cells are reported to be found in many different tissues. For example, bone marrow contains bone marrow stromal stem cells and skeletal stem cells. These in turn make bone cells called osteoblasts and osteocytes, cartilage cells ( chondrocytes) , fat or adipose cells and stromal cells that help with blood formation.

• The brain has three major cell types that are Neural stem cells. One is nerve cells called neurons. Two other types astrocytes and oligondendrocytes. These two types are non-neuronal. All types are key parts of the nervous system cells. These help rebuild and replace old or damaged cells.

• The digestive tract contains Epithelial stem cells. They are present in the linings and are able to activate as needed.

• Skin stem cells are in the basal or bottom layers of the skin and hair follicles. The skin stem cells (epidermal)form keratinocytes which go to the skin surface to form a protective layer. Follicular stem cells work with the hair follicle and the epidermis.

Both embryonic stem cells and adult stem cells have potential for usage in stem cell based therapies ( cell based regenerative therapies). Each has their own advantages and disadvantages. A major difference in the types of stem cells is the number of and specific cells they become. Embryonic stem cells can become any and all cells because they are considered pluripotent. Adult stem cells are believed to be limited to forming the cell types of their site of origin.

Another difference is that embryonic stem cells grow easily and rapidly in the culture dish. Adult stem cells are very rare in mature tissues, so obtaining cells are very difficult. It is also very difficult to expand the numbers of adult stem cells and methods to do so in a culture dish have not been completely developed.

It is believed that tissues from both embryonic and adult stem cells have differences in the likelihood of being rejected after transplantation. It is unknown whether tissues received from embryonic stem cells cause transplant rejection. There have been few clinical trials to date to test the safety and rejection potential. More research is needed in this area.

Adult stem cells ,and the tissues coming from them, are currently thought to be less likely to cause rejection after a transplant. It is believed a patient’s own cells could be grown in a culture, manipulated to become the specific needed cell type and given back to the patient. Since the stem cells and tissues come from the patients own body, these cells are less likely to be rejected by the immune system. This gives the patient a huge advantage since the current procedure to prevent rejection is by the patient taking continuous doses of immunosuppressive drugs that can cause serious side effects.

As you can see there are many potential uses for human stem cells in science and medicine. This involves ongoing research and clinical trials. The study of human embryonic stem cells will provide more information on complex human growth and development. It will help scientists to understand how the unspecified stem cells become the specific tissues and organs. Serious medical conditions like birth defects and cancer happen when cells divide abnormally. When scientists understand what genes trigger the abnormal division more information will be available on how the disease starts and develops and more importantly new treatment strategies may be developed. Recent research and development have suggested some of the factors involved. It is important, however, that techniques and procedures must be developed to safely put these factors into the cells and monitor the processes triggered by the factors introduced.

Human stem cells are used to test the safety of new medications. New medications are tested on specific cultured cells to observe for reactions or adverse effects. This needs to be done very carefully and under controlled conditions. Scientists must be able to precisely control the development of stem cells into specific cell types for the drug to get accurate information on the drugs effects and action.

The most important potential use for stem cells is creating new cells and tissues for cell based therapies such as transplantation. Donated organs and tissues are currently used to replace damaged or destroyed tissues. Unfortunately the need for transplantable organs and tissues is greater than the available supply. Stem cells offer the possibility of renewable replacement cells to treat diseases such as macular degeneration, spinal chord injuries, strokes, burns, heart disease, diabetes, and arthritis. Bone marrow transplants are already being used in treating certain types of cancer. Research and clinical trials looking into cell transplantation is ongoing and offers hope to doctors and patients alike.

Many patients have questions about clinical trials and how they help in medical research. Clinical trials are also known as Research Studies and have been used in medicine for a long time. The World Health Organization (WHO) describes a Clinical trial as a research study that assigns willing human participants to one or more health related treatments to see if the treatments are safe and effective. Clinical trials must follow a specific and pre-defined plan and protocol for the treatment of the disease being examined. Patients must sign consents to agree to participate in a Clinical Trial and must perform the specific protocol as instructed otherwise the results will be inaccurate.

Clinical trials come in 3 phases to test the effectiveness and safety of the new drug or treatment.

• Phase 1 of a clinical trial involves a few patients to see how safe the drug or treatment is. At this stage the new drug or treatment is being tested by itself to see what side effects and adverse reactions occur. The new treatment is not being compared to anything else. It is just being studied to see how it works.

• Phase2 uses a r number of patients to test the treatment or drug. The Scientific researchers have a better idea how the treatment works and how safe it is based on the results from Phase 1. This phase gives researchers a better idea of how the drug works, what exactly it does and what side effects (both minor and major) occur. The number of patients used in this phase is still small so scientists can’t get enough firm evidence to support the safety and effectiveness of the treatment so before releasing to general use, the clinical trial proceeds to Phase 3.

• Phase 3 is also known as a Randomized Clinical Trial. This phase uses a number of patients to test the treatment. In this phase the new treatment may be tested against older more established treatments to see if it is as safe and effective. It also helps determine on a scale, what the side effects are. Participants are divided into two groups, those who will use the new treatment and those who will be in the standard group that take a placebo or the standard treatment. Most phase 3 trials will randomly assign the patients to the control group or the new treatment group. Patients then report their symptoms and effects and help researchers know what effects the treatment actually has.

Patients may be asked to participate in any phase of a clinical trial. If you are interested in participating in a clinical trial or a research study, talk to your Doctor to see if there is one that is right for you and what you need to do to participate. Patients are always needed for the ongoing research in medicine, especially in the area of stem cells. If you have questions about Stem Cell and Stem Cell Research, write them down and discuss with your Doctor.

REFERENCES:

1. What are the potential uses of human stem cells and the obstacles that must be overcome before these potential uses will be realized? In Stem Cell info (http://stemcells.nih.gov/info/basics) Bethesda MD. NIH US Department of Health and Human Services 2009. Cited 2/5/15

2. What are Clinical Trials and Why Do we need them? http://www.healthtalk.org/peoples-experiences/medical-research/clinical-trials/what-are-clinical-trials-and-why-do-we-need-them. Cited 02/05/15.

3. Knowles Lori P. “What are Stem Cells and Where Do They Come From?” Stem Cell Network, For the Public,Ethics and Policy, Spring 2010. http://www.stemcellnetwork.ca/.

4. Joanne P. Shelby-Klein, BSN, RN