Stem cells are cells with the potential to develop into many different types of cells and serve as a repair system for the body.
There are two main types of stem cells: embryonic stem cells and adult stem cells.
Stem cells are different from other cells in the body in three ways:
- they can divide and renew themselves over a long time;
- they are unspecialized, so they cannot do specific functions in the body;
- they have the potential to become specialized cells, such as muscle cells, blood cells, and brain cells.
Doctors and scientists are excited about stem cells because they could help in many different areas of health and medical research. Studying stem cells may help explain how serious conditions such as birth defects and cancer come about.
Stem cells may one day be used to make cells and tissues for the therapy of many diseases. Examples include Parkinson’s disease, Alzheimer’s disease, spinal cord injury, heart disease, diabetes, and arthritis.
What are the unique properties of all stem cells?
Stem cells have unique abilities to self-renew and recreate functional tissues.
Stem cells have the ability to self-renew.
Unlike muscle cells, blood cells, or nerve cells — which do not normally replicate — stem cells may replicate many times. When a stem cell divides, the resulting two daughter cells may be:
1) both stem cells,
2) a stem cell and a more differentiated cell, or
3) both more differentiated cells.
What controls the balance between these types of divisions to maintain stem cells at an appropriate level within a given tissue is not yet well known.
Discovering the mechanism behind self-renewal may make it possible to understand how cell fate (stem vs. non-stem) is regulated during normal embryonic development and post-natally, or misregulated as during aging, or even in the development of cancer. Such information may also enable scientists to grow stem cells more efficiently in the laboratory.
The specific factors and conditions that allow pluripotent stem cells to remain undifferentiated are of great interest to scientists. It has taken many years of trial and error to learn to derive and maintain pluripotent stem cells in the laboratory without the cells spontaneously differentiating into specific cell types.
Stem cells have the ability to recreate functional tissues.
Pluripotent stem cells are undifferentiated; they do not have any tissue-specific characteristics (such as morphology or gene expression pattern) that allow them to perform specialized functions. Yet they can give rise to all of the differentiated cells in the body, such as heart muscle cells, blood cells, and nerve cells.
On the other hand, adult stem cells differentiate to yield the specialized cell types of the tissue or organ in which they reside, and may have to define morphological features and patterns of gene expression reflective of that tissue.
Different types of stems cells have varying degrees of potency; that is, the number of different cell types that they can form. While differentiating, the cell usually goes through several stages, becoming more specialized at each step.
Scientists are beginning to understand the signals that trigger each step of the differentiation process. Signals for cell differentiation include factors secreted by other cells, physical contact with neighboring cells, and certain molecules in the microenvironment.
How are stem cells grown in the laboratory?
Growing cells in the laboratory is known as “cell culture.” Stem cells can proliferate in laboratory environments in a culture dish that contains a nutrient broth known as a culture medium (which is optimized for growing different types of stem cells). Most stem cells attach, divide, and spread over the surface of the dish.
The culture dish becomes crowded as the cells divide, so they need to be re-plated in the process of subculturing, which is repeated periodically many times over many months. Each cycle of subculturing is referred to as a “passage.” The original cells can yield millions of stem cells. At any stage in the process, batches of cells can be frozen and shipped to other laboratories for further culture and experimentation.
How do we “reprogram” regular cells to make iPSCs?
Differentiated cells, such as skin cells, can be reprogrammed back into a pluripotent state. Reprogramming is achieved over several weeks by forced expression of genes that are known to be master regulators of pluripotency.
At the end of this process, these master regulators will remodel the expression of an entire network of genes. Features of differentiated cells will be replaced by those associated with the pluripotent state, essentially reversing the developmental process.
How are stem cells stimulated to differentiate?
As long as the pluripotent stem cells are grown in culture under appropriate conditions, they can remain undifferentiated. To generate cultures of specific types of differentiated cells, scientists may change the chemical composition of the culture medium, alter the surface of the culture dish, or modify the cells by forcing the expression of specific genes.
Through years of experimentation, scientists have established some basic protocols, or “recipes,” for the differentiation of pluripotent stem cells into some specific cell types.
What laboratory tests are used to identify stem cells?
At various points during the process of generating stem cell lines, scientists test the cells to see whether they exhibit the fundamental properties that make them stem cells. These tests may include:
- Verifying the expression of multiple genes that have been shown to be important for the function of stem cells.
- Checking the rate of proliferation.
- Checking the integrity of the genome by examining the chromosomes of selected cells.
Demonstrating the differentiation potential of the cells by removing signals that maintain the cells in their undifferentiated state, which will cause pluripotent stem cells to spontaneously differentiate, or by adding signals that induce adult stem cells to differentiate into appropriate cell phenotypes.
How are stem cells used in biomedical research and therapies?
Given their unique regenerative abilities, there are many ways in which human stem cells are being used in biomedical research and therapeutics development.
Scientists can use stem cells to learn about human biology and for the development of therapeutics. A better understanding of the genetic and molecular signals that regulate cell division, specialization, and differentiation in stem cells can yield information about how diseases arise and suggest new strategies for therapy.
Scientists can use iPSCs made from a patient and differentiate those iPSCs to create “organoids” (small models of organs) or tissue chips for studying diseased cells and testing drugs, with personalized results.
An important potential application is the generation of cells and tissues for cell-based therapies, also called tissue engineering. The current need for transplantable tissues and organs far outweighs the available supply.
Stem cells offer the possibility of a renewable source. There is typically a very small number of adult stem cells in each tissue, and once removed from the body, their capacity to divide is limited, making the generation of large quantities of adult stem cells for therapies difficult. In contrast, pluripotent stem cells are less limited by starting material and renewal potential.
To realize the promise of stem cell therapies in diseases, scientists must be able to manipulate stem cells so that they possess the necessary characteristics for successful differentiation, transplantation, and engraftment.
Scientists must also develop procedures for the administration of stem cell populations, along with the induction of vascularization (supplying blood vessels), for the regeneration and repair of three-dimensional solid tissues.
To be useful for transplant purposes, stem cells must be reproducibly made to:
- Proliferate extensively and generate sufficient quantities of cells for replacing lost or damaged tissues.
- Differentiate into the desired cell type(s).
- Survive in the recipient after transplant.
- Integrate into the surrounding tissue after transplant.
- Avoid rejection by the recipient’s immune system.
- Function appropriately for the duration of the recipient’s life.
While stem cells offer exciting promise for future therapies, significant technical hurdles remain that will likely only be overcome through years of intensive research.
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