Stem Cells

Explore the general process and duties of stem cells:

1. Self-Renewal: Stem cells have the unique ability to divide and produce more cells of the same type. This process is called self-renewal and ensures a constant supply of stem cells throughout a person’s life. During self-renewal, stem cells can either divide symmetrically, giving rise to two identical stem cells, or asymmetrically, producing one stem cell and one specialized cell.

2. Differentiation: Stem cells can differentiate into specialized cell types through a process called differentiation. This is controlled by various signals from the surrounding microenvironment, known as the stem cell niche. The niche provides cues that direct the stem cells to adopt specific fates and mature into various cell types, such as neurons, muscle cells, or liver cells. The differentiation process is tightly regulated and essential for the proper development and functioning of tissues and organs.

3. Tissue Repair and Regeneration: Stem cells play a critical role in tissue repair and regeneration. When tissues are damaged due to injury or disease, stem cells are activated and mobilized to the site of injury. They can differentiate into the required cell types to replace the damaged cells, promoting tissue healing and restoration of function. This regenerative capacity is particularly evident in organs with high cell turnover rates, such as the skin, blood, and gastrointestinal tract.

4. Disease Treatment and Research: Stem cells have revolutionized the field of regenerative medicine and hold immense potential for treating various diseases. Their ability to differentiate into specific cell types offers opportunities for cell-based therapies, such as replacing damaged neurons in Parkinson’s disease or restoring heart tissue after a heart attack. Stem cells are also valuable tools for studying diseases in the laboratory, as they can be used to generate disease-specific cells for research, drug testing, and understanding disease mechanisms.

5. Ethical Considerations: It is important to note that the use of embryonic stem cells raises ethical concerns due to the necessity of destroying embryos. Researchers are actively exploring alternative approaches, such as iPSCs and ASCs, to address these concerns and still harness the therapeutic potential of stem cells.

There is ongoing research to better understand potential benefits and the risks of using stem cells, and the need to develop new techniques for using them safely and effectively in medicine. The field of stem cell research and new therapies continues to evolve rapidly and researchers are constantly exploring new applications for stem cells in the field of medicine.

Stem cells can be sourced from various tissues in the human body, including adipose tissue as adult stem cells. Human mesenchymal stem cells are derived from umbilical cord tissue or blood. Their regenerative capabilities allow for tissue regeneration, decreased inflammation, and pain relief, benefitting patients with rheumatoid arthritis, spinal cord injuries, and neurological diseases. Stem Cell-based therapies harness the regenerative properties of stem cells. These undifferentiated cells have the potential to differentiate into specialized cells, such as blood cells, neural cells, and more.

I. Stem Cell Basics

Stem cells have the remarkable potential to renew themselves. They can develop into many different cell types in the body during early life and growth. Researchers study many different types of stem cells. There are several main categories: the “pluripotent” stem cells (embryonic stem cells and induced pluripotent stem cells) and nonembryonic or somatic stem cells (commonly called “adult” stem cells). Pluripotent stem cells have the ability to differentiate into all of the cells of the adult body. Adult stem cells are found in a tissue or organ and can differentiate to yield the specialized cell types of that tissue or organ.

Pluripotent stem cells

Early mammalian embryos at the blastocyst stage contain two types of cells – cells of the inner cell mass, and cells of the trophectoderm. The trophectodermal cells contribute to the placenta. The inner cell mass will ultimately develop into the specialized cell types, tissues, and organs of the entire body of the organism. Previous work with mouse embryos led to the development of a method in 1998 to derive stem cells from the inner cell mass of preimplantation human embryos and to grow human embryonic stem cells (hESCs) in the laboratory. In 2006, researchers identified conditions that would allow some mature human adult cells to be reprogrammed into an embryonic stem cell-like state. Those reprogramed stem cells are called induced pluripotent stem cells (iPSCs).

Adult stem cells

Throughout the life of the organism, populations of adult stem cells serve as an internal repair system that generates replacements for cells that are lost through normal wear and tear, injury, or disease. Adult stem cells have been identified in many organs and tissues and are generally associated with specific anatomical locations. These stem cells may remain quiescent (non-dividing) for long periods of time until they are activated by a normal need for more cells to maintain and repair tissues.

II. What are the unique properties of all stem cells?

Stem cells have unique abilities to self-renew and to recreate functional tissues.

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 defining 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.

III. How do you culture stem cells in the laboratory?

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 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 are adult stem cells reprogrammed 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 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.

IV. 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.

Understanding the biology of disease and testing drugs

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.

Cell-based therapies

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 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:

• a) Proliferate extensively and generate sufficient quantities of cells for replacing lost or damaged tissues.
• b) Differentiate into the desired cell type(s).
• c) Survive in the recipient after transplant.
• d) Integrate into the surrounding tissue after transplant.
• e) Avoid rejection by the recipient’s immune system.
• f) Function appropriately for the duration of the recipient’s life.
•  
• * A stem cell is a cell with the unique ability to develop into specialised cell types in the body.
• i) They are being used to replace cells and tissues that have been damaged or lost due to disease.
• ii) They serve as a repair system for the body.
• iii)They can divide over and over again to produce new cells and as they divide, they change into other cell types that make up our body.