Why are Stem Cells Important?
Stem cells have the amazing potential to develop into a variety of different cell types during the body’s early life and growth. Furthermore, in many tissues they function as a kind of internal repair system, essentially dividing limitlessly to replenish other cells while the person (or animal) is still alive. When a stem cell divides, each new cell has the potential to remain a stem cell or convert into another type of cell with a more specialized role – e.g. a muscle cell, a red blood cell, or a brain cell.
Stem cells distinguish themselves from other cell types by two significant characteristics:
- They are unspecialized cells capable of renewing themselves through cell division, often after extended periods of inactivity.
- Under specific physiologic or experimental conditions, they can be induced to become tissue or organ-specific cells with specialized functions.
In certain organs like the gut or bone marrow, stem cells normally divide to repair and replace damaged or worn out tissues. In other organs, however, such as the heart and pancreas, stem cells only divide under special conditions.
In the past, scientists primarily worked with two types of stems cells from humans and animals: embryonic stem cells and non-embryonic stem cells (aka “somatic” or “adult” stem cells). In 1981, researchers first discovered methods to derive embryonic stem cells from early mouse embryos. Then in 1998, studying the biology of mouse stem cells eventually led to the discovery of a method to derive stem cells from human embryos and grow the cells in a lab. These cells are called human embryonic stem cells. The embryos utilized in these studies were created for reproductive purposes via in vitro fertilization procedures. When they were no longer needed for that purpose, they were donated for research with the informed consent of the donor. In 2006, scientists made another breakthrough by identifying the conditions that would permit certain specialized adult cells to be genetically “re-programmed” to assume a stem cell-like state. These new type of stem cells are called induced pluripotent stem cells (iPSCs).
Stem cells are vital to living organisms for a variety of reasons. In a 3 to 5-day-old embryo (called a “blastocyte”) the inner cells produce the organism’s entire body, including all of the specialized cell types and organs such as the heart, lungs, skin, eggs, sperm, and other tissues. In certain adult tissues, such as bone marrow, brain, and muscle, distinct populations of adult stem cells generate replacements for cells which are lost to normal wear and tear, disease, or injury.
With their unique regenerative abilities, stem cells offer new opportunities to treat diseases like diabetes and heart disease. Furthermore, our understanding about how to use these cells to treat disease continues to grow and has spawned the field of regenerative or reparative medicine.
Laboratory work enables scientists to learn more about stem cells’ core properties and what distinguishes them specialized cell types. Scientists are already using stem cells in the lab to screen new drugs and to develop models to study normal growth and identify the causes of birth defects.
Ongoing stem cell research also continues to expand our knowledge about how an organism develops from a single cell and how healthy cells replenish damaged cells in adult organisms. Stem cell research is among the most fascinating areas of modern biology, but, as with many growing scientific fields, research about stem cells raises new scientific question just as quickly as it generates new discoveries.
The Three General Properties of All Stem Cells
Regardless of their source, all stem cells have three general properties: (i) they capable of dividing and renewing themselves for long periods, (ii) they are unspecialized, and (iii) they can produce specialized cell types.
Stem cells are capable of dividing and renewing themselves for long periods.
Unlike blood cells, muscle cells, or nerve cells (which normally do NOT replicate) stem cells may “proliferate,” or replicate numerous times. In a lab, an initial population of stem cells can proliferate into millions of cells. If the resulting yield of cells remain unspecialized – like the parent stem cells – the cells are said to be capable of long-term self-renewal.
There are two fundamental questions about stem cells’ long-term self-renewal that require greater understanding:
- Why can embryonic stem cells proliferate for a year (or more) in the lab WITHOUT differentiating, but most adult stem cells cannot; and
- What factors in living organisms normally regulate stem cell proliferation and self-renewal?
Answering these questions might allow us to understand how cell proliferation is regulated during normal embryonic development or during the abnormal cell division that leads to cancer. Such knowledge would also help researchers become more proficient at growing both embryonic and non-embryonic stem cells in a laboratory.
The specific factors that permit stem cells to stay unspecialized are a subject of great interest to researchers. It took many years of trial and error to determine how to derive and maintain stem cells in a lab without them spontaneously differentiating into specific cell types. For example, it took twenty years to learn how to grow human embryonic stem cells in the lab after first developing conditions for growing mouse stem cells. Similarly, scientists must first understand the specific signals that enable a non-embryonic (adult) stem cell population to proliferate and remain unspecialized before they can grow large numbers of unspecialized adult stem cells in the lab.
Stem cells are unspecialized.
One of the fundamental properties of stems cells is that they do NOT have any tissue-specific structures that allow them to perform specialized functions. For example, a stem cell cannot collaborate with neighboring cells to pump blood through the body like a heart muscle cell, and it cannot carry oxygen molecules through the bloodstream like a red blood cell. However, unspecialized stem cells can give rise to specialized cells such as heart muscle cells, blood cells, or nerve cells.
Stem cells can give rise to specialized cells.
The process by which unspecialized stem cells give rise to specialized cells is called differentiation. When differentiating, the cell usually goes through several stages, becoming more and more specialized with each step. Researchers continue explore the signals inside and outside cells that trigger each stage of the differentiation process. The internal signals are controlled by a cell’s genes, which are interspersed across long strands of DNA and carry coded instructions for all cellular structures and functions. On the other hand, the external signals for differentiation include chemicals secreted by other cells, physical contact with adjacent cells, and specific molecules in the fluid surrounding a cell (aka the “microenvironment”). During differentiation, the interaction of these signals causes the cell’s DNA to acquire epigenetic marks which limit DNA expression in the cell and can be passed on through cell division.
Scientists continue to study the signals related to differentiation, with the hope that they may discover new ways to control stem cells differentiation in the lab – thereby enabling the growth of cells or tissue that can be used for specific purposes (e.g. cell-based therapies).
Adult stem cells typically generate the cell types of the tissue in which they reside. For example, a blood-forming adult stem cell in the bone marrow – which is called a hematopoietic stem cell – normally gives rise to the many types of blood cells. It is generally accepted that the same blood-forming stem cell in the marrow CANNOT give rise to the cells of a very different tissue, such as nerve cells in the brain. Some experiments, however, have purported to demonstrate that stem cells for one tissue may give rise to cells types of a completely different. This remains an area of great debate within the research community and highlights that additional research using adult stem cells is required to understand their full potential.
Embryonic Stem Cell Basics
As their name suggests, embryonic stem cells are derived from embryos. Most embryonic stem cells are derived from embryos that develop from eggs that have been fertilized in vitro (at an in vitro fertilization clinic). These eggs are donated for research purposes with the informed consent of the donors. For clarity, they are NOT derived from eggs fertilized in a woman’s body.
Growing Embryonic Stem Cells
Growing cells in a lab is called cell culture. Human embryonic stem cells (hESCs) are created by transferring cells from a pre-implantation-stage embryo into a laboratory culture dish that contains a nutrient broth known as culture medium. The cells divide and spread across the surface of the dish. If the cells survive, divide and multiply enough to fill the dish, they are carefully plated into several fresh culture dishes. The process of re-plating (subculturing) the cells is repeated many times over the course of many months. Each cycle of subculturing the cells is called a passage. Once a viable cell line is established, the original cells can yield millions of embryonic stem cells. Embryonic stem cells that proliferate in cell culture for six or more months without differentiating, are pluripotent. If these pluripotent cells appear genetically normal they are referred to as an embryonic stem cell line. Furthermore, at any stage in the process, batches of cell lines can be frozen and transported to other labs for further culture and experimentation.
Identifying Embryonic Stem Cells
During the process of generating embryonic stem cell lines, researchers test the cells to confirm they exhibit the fundamental properties to be embryonic stem cells. This process is called characterization. Scientists who study embryonic stem cells have yet to agree on a standard panel of tests to measure the cells’ fundamental properties. This, however, has not stopped labs from using the following kinds of tests for stem cell characterization:
- Growing and subculturing stem cells for many months ensures that the cells are capable of long-term growth and self-renewal. Scientists examine the cultures through a microscope to see that the cells appear healthy and remain undifferentiated.
- Techniques to verify the presence of transcription factors that are typically produced by undifferentiated cells. Transcription factors help turn genes on and off at the right time, which is key to the process of cell differentiation. Two of the most important transcription factors are Nanog and Oct4, which are associated with maintaining the stem cells in an undifferentiated state, capable of self-renewal.
- Techniques to verify the presence of particular cell surface markers that are typically produced by undifferentiated cells.
- Examining the chromosomes using a microscope to access whether the chromosomes are damaged or if the number of chromosomes has changed. It does not, however, detect genetic mutations.
- Verifying that the cells can be re-grown, or subcultured after freezing, thawing, and re-plating.
- Testing whether human embryonic stem cells are pluripotent by: (i) allowing the cells to differentiate spontaneously in cell culture; (ii) manipulating the cells so they will differentiate to form cells characteristic of the three germ layers; or (iii) injecting the cells into a mouse with a suppressed immune system to test for the formation of a benign tumor called a teratoma. Teratomas typically contain a combination of many differentiated or partly differentiated cell types – this indicates that the embryonic stem cells are capable of differentiating into multiple cell types.
Stimulating Embryonic Stem Cells to Differentiate
To generate cultures of specific types of differentiated cells (e.g. heart muscle cells, blood cells, or nerve cells) scientists try to control the differentiation of embryonic stem cells by: (i) altering the composition of the culture medium, (ii) altering the surface of the culture dish, or (iii) modifying the cells by inserting specific genes.
Through years of experimentation, scientists have established some basic protocols or “recipes” for the directed differentiation of embryonic stem cells into some specific cell types.
If scientists can predictably direct the differentiation of embryonic stem cells into specific cell types, they may be able to use the resulting, differentiated cells to treat certain diseases in the future. Diseases that might be treated by transplanting cells generated from human embryonic stem cells include diabetes, duchenne’s muscular dystrophy, heart disease, traumatic spinal cord injury, vision loss, and hearing loss.