Tuesday, February 28, 2017

Stem Cell Basics

Stem cells are the foundation from which all parts of the human body grow.

Cells in the human body

The human body comprises more than 200 types of cells, and every one of these cell types arises from the zygote, the single cell that forms when an egg is fertilized by a sperm. Within a few days, that single cell divides over and over again until it forms a blastocyst, a hollow ball of 150 to 200 cells that give rise to every single cell type a human body needs to survive, including the umbilical cord and the placenta that nourishes the developing fetus.

Basic cell biology

Each cell type has its own size and structure appropriate for its job. Skin cells, for example, are small and compact, while nerve cells that enable you to wiggle your toes have long, branching nerve fibers called axons that conduct electrical impulses.
Cells with similar functionality form tissues, and tissues organize to form organs. Each cell has its own job within the tissue in which it is found, and all of the cells in a tissue and organ work together to make sure the organ functions properly.
Human CellRegardless of their size or structure, all human cells start with these things in common:
  • nucleus that contains DNA, the genetic library for the entire body. Different cells read and carry out different instructions from the DNA, depending on what those cells are designed to do. Your DNA determines virtually everything about your body, from the color of your eyes to your blood type and even how susceptible you are to certain diseases. Some diseases and conditions, such as color blindness, also are passed down through DNA.
  • Cytoplasm – the liquid outside the nucleus. The cytoplasm contains various components that make the materials that the cell needs to do its job.
  • Cell DivisionThe cell membrane – the surface of the cell, a complex structure that sends and receives signals from other cells and lets material in and out of the cell. Cells have to be able to communicate to work together in tissues and organs.
Most cells divide. Shortly before division, the DNA replicates and then the cell divides into two daughter cells. Each has a complete copy of the original cell’s DNA, cytoplasm and cell membrane.

About stem cells

Stem cells are the foundation of development in plants, animals and humans. In humans, there are many different types of stem cells that come from different places in the body or are formed at different times in our lives. These include embryonic stem cells that exist only at the earliest stages of development and various types of tissue-specific (or adult) stem cells that appear during fetal development and remain in our bodies throughout life.
Stem cells are defined by two characteristics:
  • They can make copies of themselves, or self-renew
  • They can differentiate, or develop, into more specialized cells
Beyond these two things, though, stem cells differ a great deal in their behaviors and capabilities.
Embryonic stem cells are pluripotent, meaning they can generate all of the body’s cell types but cannot generate support structures like the placenta and umbilical cord.
Other cells are multipotent, meaning they can generate a few different cell types, generally in a specific tissue or organ.
As the body develops and ages, the number and type of stem cells changes. Totipotent cells are no longer present after dividing into the cells that generate the placenta and umbilical cord. Pluripotent cells give rise to the specialized cells that make up the body’s organs and tissues. The stem cells that stay in your body throughout your life are tissue-specific, and there is evidence that these cells change as you age, too – your skin stem cells at age 20 won’t be exactly the same as your skin stem cells at age 80.

Types of Stem Cells

Stem cells

Stem cells are the foundation for every organ and tissue in your body. There are many different types of stem cells that come from different places in the body or are formed at different times in our lives. These include embryonic stem cells that exist only at the earliest stages of development and various types of tissue-specific (or adult) stem cells that appear during fetal development and remain in our bodies throughout life.
All stem cells can self-renew (make copies of themselves) and differentiate (develop into more specialized cells). Beyond these two critical abilities, though, stem cells vary widely in what they can and cannot do and in the circumstances under which they can and cannot do certain things. This is one of the reasons researchers use all types of stem cells in their investigations.
In this section:
  • Embryonic stem cells
  • Tissue-specific stem cells
  • Mesenchymal stem cells
  • Induced pluripotent stem cells

Embryonic stem cells

Embryonic stem cells are obtained from the inner cell mass of the blastocyst, a mainly hollow ball of cells that, in the human, forms three to five days after an egg cell is fertilized by a sperm. A human blastocyst is about the size of the dot above this “i.”
In normal development, the cells inside the inner cell mass will give rise to the more specialized cells that give rise to the entire body—all of our tissues and organs. However, when scientists extract the inner cell mass and grow these cells in special laboratory conditions, they retain the properties of embryonic stem cells.
Embryonic stem cells are pluripotent, meaning they can give rise to every cell type in the fully formed body, but not the placenta and umbilical cord. These cells are incredibly valuable because they provide a renewable resource for studying normal development and disease, and for testing drugs and other therapies. Human embryonic stem cells have been derived primarily from blastocysts created by in vitro fertilization (IVF) for assisted reproduction that were no longer needed.

Tissue-specific stem cells

Tissue-specific stem cells (also referred to as somatic or adult stem cells) are more specialized than embryonic stem cells. Typically, these stem cells can generate different cell types for the specific tissue or organ in which they live.
For example, blood-forming (or hematopoietic) stem cells in the bone marrow can give rise to red blood cells, white blood cells and platelets. However, blood-forming stem cells don’t generate liver or lung or brain cells, and stem cells in other tissues and organs don’t generate red or white blood cells or platelets.
Some tissues and organs within your body contain small caches of tissue-specific stem cells whose job it is to replace cells from that tissue that are lost in normal day-to-day living or in injury, such as those in your skin, blood, and the lining of your gut.
Tissue-specific stem cells can be difficult to find in the human body, and they don’t seem to self-renew in culture as easily as embryonic stem cells do. However, study of these cells has increased our general knowledge about normal development, what changes in aging, and what happens with injury and disease.

Mesenchymal Stem Cells:
You may hear the term “mesenchymal stem cell” or MSC to refer to cells isolated from stroma, the connective tissue that surrounds other tissues and organs. Cells by this name are more accurately called “stromal cells” by many scientists. The first MSCs were discovered in the bone marrow and were shown to be capable of making bone, cartilage and fat cells. Since then, they have been grown from other tissues, such as fat and cord blood. Various MSCs are thought to have stem cell, and even immunomodulatory, properties and are being tested as treatments for a great many disorders, but there is little evidence to date that they are beneficial. Scientists do not fully understand whether these cells are actually stem cells or what types of cells they are capable of generating. They do agree that not all MSCs are the same, and that their characteristics depend on where in the body they come from and how they are isolated and grown.

Induced pluripotent stem cells

Induced pluripotent stem (iPS) cells are cells that have been engineered in the lab by converting tissue-specific cells, such as skin cells, into cells that behave like embryonic stem cells. IPS cells are critical tools to help scientists learn more about normal development and disease onset and progression, and they are also useful for developing and testing new drugs and therapies.
While iPS cells share many of the same characteristics of embryonic stem cells, including the ability to give rise to all the cell types in the body, they aren’t exactly the same. Scientists are exploring what these differences are and what they mean. For one thing, the first iPS cells were produced by using viruses to insert extra copies of genes into tissue-specific cells. Researchers are experimenting with many alternative ways to create iPS cells so that they can ultimately be used as a source of cells or tissues for medical treatments.

Stem Cells and Research

Stem cell science informs our understanding of the human body and approach to medicine.

These are just a few of the ways stem cells are being used:
  • To study normal human development. Scientists are investigating how stem cells form tissues and organs, how aging impacts their function and their role in various diseases and conditions. A better understanding of the inner working of living organisms leads to earlier detection, better diagnosis and more effective treatments for diseases and injury.
  • In drug discovery, which is the process by which new drugs are identified for a particular disease. Scientists can use stem cells, or tissues grown from them, to search for new drugs that improve their function or alter the progress of disease, as well as to test how drugs might affect different organs (for example, the liver or the kidneys), or how they might affect different people.
  • For cell replacement. Scientists are exploring how to use stem cells to generate tissue that, when transplanted, will take the place of tissue damaged by disease, aging or injury. For example, transplantation of healthy retinal pigment epithelial cells to the eye to replace those lost in macular degeneration is now being tested in clinical trials.
  • For endogenous, or self, repair. Scientists are also exploring ways to stimulate self-repair, coaxing stem cells in the human body to generate healthy cells to heal damaged tissue from within or to prevent further damage.
Stem cell research holds tremendous promise for medical treatments, but scientists still have much to learn about how stem cells, and the specialized cells they generate, work in the body and their capacity for healing. Learn more about clinical translation, the process through which science becomes medicine.

How Science Becomes Medicine

The process by which science becomes medicine is designed to minimize harm and maximize effectiveness.

There is a well-established path by which scientific discoveries are developed into new medical treatments

Clinical translation is the multi-step process of turning scientific discoveries made in the laboratory into real-world medical treatments. This process involves testing a potential new treatment in a series of experiments to assess its safety and effectiveness. When tested on people in the context of a rigorous clinical trial, many possible new treatments fail to be proven safe and effective.
In this section:
  • Basic research
  • Preclinical research
  • Clinical research and patient protections
  • Approval for use

Basic research

Basic research involves figuring out how living organisms, from the cellular level up to the whole animal or person, work and also what can go wrong in disease or injury. Experiments in the lab are where scientists come to understand and test the scientific principles that underlie important medical discoveries.
Scientists in every field are taught to follow the scientific method, a process designed to acquire new knowledge in an objective manner. The basic steps of the scientific method are:
  1. Ask a question
  2. Background research
  3. Come up with a hypothesis, a proposed explanation for the question
  4. Test the hypothesis in a manner in which you can either prove or disprove the hypothesis
  5. Analyze the results of the testing
  6. Make a conclusion
 Scientific Method
Though the scientific method is often presented as a linear sequence of steps, new information or thinking might cause a scientist to back up and repeat steps in the process. Not all steps take place in every scientific inquiry, and they are not always approached in the same order, thus, the scientific method is best considered as general principles.
A vital part of the research process is replication and external (or peer) review. Scientists open up their methods, results and conclusions to the scrutiny of outside experts, typically through publication in peer-reviewed journals. Other scientists replicate the same experiments to reach the same outcomes. In this manner, scientists regularly collaborate with and build upon the discoveries of their peers.

Preclinical research

Preclinical research builds upon the findings of basic research and the understanding gained of disease. It involves the translation of this scientific knowledge into the development of potential treatments. Scientists study how these new treatments work in animals and may also test new treatments on lab-grown animal tissues or human tissues.  Just because a treatment shows promise in an animal, however, does not mean it will be effective in a human, which is why clinical trials are so important.

Clinical research and patient protections

If the results of preclinical research are promising, it may progress to clinical research, or testing in humans.
Clinical trials start with a small number of people and are focused on testing safety. As the procedures are perfected and the risks evaluated, the number of participants is gradually increased and the effectiveness of the treatment is more closely examined. Learn more about Clinical Trials here.
Sometimes, in attempting new surgical techniques or where the disease or condition is rare, treatments might be tried on just one or two people outside the confines of a clinical trial.
During the clinical trial process, there are a number of checks to protect the rights of patients.
Fundamental to the process are:
  • Monitoring of experimental treatments for patient safety and ethical practice. Before beginning, trials should be carefully reviewed by a group of people who together have broad expertise and experience in research, medicine and ethics. These groups, often called Institutional Review Boards (IRBs) or medical ethics review committees, evaluate a number of factors, including the potential risks weighted against the potential benefits.
  • Oversight by regulatory agencies. National oversight agencies, such as the European Medicines Agency (EMA), the U.S. Food and Drug Administration (FDA) or Japan’s Pharmaceuticals and Medical Devices Agency (PMDA), authorize and monitor the development of new treatments. The nature of regulatory agencies and their responsibilities vary from country to country, but most enforce a code of conduct or guidelines for researchers and clinicians to follow to promote safe and effective medical practice.
If you are thinking about a clinical trial for yourself or a loved one, learn more about things you should consider here.

Approval for use

In many countries, a national agency reviews clinical research for evidence of safety and effectiveness, and then approves medical treatments for use by patients. The manner in which medical treatments are marketed is also regulated to ensure companies do not make health claims related to their products that have not been proven through the trial process.
However, the field of stem cell science is new and rapidly changing, and regulation is still catching up. There may come a time when stem cell treatments are regulated consistently by governments across the world. Until such time, people investigating stem cell treatments need to be aware of what is and isn’t regulated in the countries in which they seek treatment. A lack of regulation does not constitute approval or suggest safety or effectiveness. For example, clinics may offer autologous (from your own body) stem cell treatments, which may not be subject to oversight if the cells are minimally manipulated. However, cells taken from an individual are not necessarily safe for use in or as therapy for that same individual.

Buyers beware

Perhaps you’ve heard of “snake oil,” which comes from the 19th century practice of advertising a single elixir as a remedy for all sorts of ailments without clear evidence of quality or health benefit. Unfortunately, false advertising and exaggerated claims are still a problem, and unproven stem cell treatments are among the miracle cures being sold today. Be aware of these things to know if you are considering a stem cell treatment.


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