STEM CELL part 42

Although isolated instances of transdifferentiation have been observed in some vertebrate species, whether this phenomenon actually occurs in humans is under debate by the scientific community. Instead of transdifferentiation, the observed instances may involve fusion of a donor cell with a recipient cell. Another possibility is that transplanted stem cells are secreting factors that encourage the recipient's own stem cells to begin the repair process. Even when transdifferentiation has been detected, only a very small percentage of cells undergo the process.

STEM CELL part 41

Transdifferentiation

A number of experiments have reported that certain adult stem cell types can differentiate into cell types seen in organs or tissues other than those expected from the cells' predicted lineage (i.e., brain stem cells that differentiate into blood cells or blood-forming  cells that differentiate into cardiac muscle cells, and so forth). This reported phenomenon is called transdifferentiation.

STEM CELL part 40

Skin stem cells occur in the basal layer of the epidermis and at the base of hair follicles. The epidermal stem cells give rise to keratinocytes, which migrate to the surface of the skin and form a protective layer. The follicular stem cells can give rise to both the hair follicle and to the epidermis

STEM CELL part 39

Epithelial stem cells in the lining of the digestive tract occur in deep crypts and give rise to several cell types:

Absorptive cells, goblet cells, Paneth cells, and enteroendocrine cells

STEM CELL part 38

Neural stem cells in the brain give rise to its three major cell types:

Nerve cells (neurons) and two categories of non-neuronal cells-astrocytes and oligodendrocytes

STEM CELL part 37

Mesenchymal stem cells have been reported to be present in many tissues. Those from bone marrow (bone marrow stromal stem cells, skeletal stem cells) give rise to a variety of cell types: bone cells (osteoblasts and osteocytes), cartilage cells (chondrocytes), fat cells (adipocytes), and stromal cells that support blood formation. However, it is not yet clear how similar or dissimilar mesenchymal cells derived from non-bone marrow sources are to those from bone marrow stroma.

STEM CELL part 36

Hematopoietic stem cells give rise to all the types of blood cells:

Red blood cells, B lymphocytes, T lymphocytes, natural killer cells, netrophils, basophils, eosinophils, monocytes, and macrophages.

STEM CELL part 35

Normal differentiation pathways of adult stem cells. In a living animal, adult stem cells are available to divide for a long period, when needed, and can give rise to mature cell types that have characteristic shapes and specialized structures and functions of a particular tissue. The following are examples of differentiation pathways of adult stem cells that have been demonstrated in vitro or in vivo.

STEM CELL part 34

What is known about asult stem cell differentiation?

Scientists have reported that adult stem cells occur in many tissues and that they enter normal differentiation pathways to form the specialized cell types of the tissue in which they reside.

STEM CELL part 33

Importantly, it must be demonstrated that a single adult stem cell can generate a line of genetically identical cells that then gives rise to all appropriate differentiated cell types of the tissue.  To confirm experimentally that a putative adult stem cell is indeed a stem cells in culture, and/or that a purified population of these candidate stem cells can repopulate or reform the tissue after transplant into an animal

STEM CELL part 32

What tests are used to identify adult stem cells?

Scientists often use one or more of the following methods to identify adult stem cells:

• Label the cells in a living tissue with molecular markers and then determine the specialized cell types they generate
• Remove the cells from a living animal, label them in cell culture, and transplant them back into another animal to determine whether the cells replace (or "repopulate") their tissue of origin

STEM CELL part 31

Typically, there is a very small number of stem cells in each tissue, and once removed from the body, their capacity to divide is limited, making generation of large quantities of stem cells difficult. Scientists in many laboratories are trying  to find better ways to grow large quantities of adult stem cells in  cell culture and to manipulate them to generate specific cell types so they can be used to treat injury or disease. Some examples of potential treatments include regenerating bone using cells derived from bone marrow stroma, developing insulin-producing cells for type 1 diabetes, and repairing damaged heart muscle following a heart attack with cardiac muscle cells.

STEM CELL part 30

Where are adult stem cells found, and what do they normally do?

Adult stem cells have been identified in many organs and tissue, including brain, bone marrow, peripheral blood, blood vessels, skeletal muscle, skin, teeth, heart, gut, liver, ovarian epithelium, and testis. They are thought to reside in a specific area of each tissue (called a "stem cell niche"). In many tissues, current evidence suggests that some types of stem cells are pericytes, cells that compose the outermost layer of small blood vessels. 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 tissues, or by disease or tissue injury.

STEM CELL part 29

In the 1960s, scientists who were studying rats discovered two regions of the brain that contained dividing cells that ultimately become nerve cells. Despite these reports, most scientists believed that the adult brain could not generate new nerve cells. It was not until the 1990s that scientists agreed that the adult brain does contain stem cells that are able to generate the brains's three major cell types-astrocytes and oligodendrocytes, which are non-neuronal cells, and neurons, or nerve cells.

STEM CELL part 28

The history of research on adult stem cells in the 1950s, researchers discovered  that the bone marrow contains at least two kinds of stem cells. One population, called hematopoietic stem cells, forms all the types of blood cells in the body. A second population, called bone marrow stromal stem cells (also called mesenchymal stem cells, or skeletal stem cells by some) were discovered a few years later. These non-hematopoetic stem cells make up a small proportion of the stromal cell population in the bone marrow, and can generate bone, cartilage, fat, cells that support the formation of blood, and fibrous connective tissue.

STEM CELL part 27

Research on adult stem cells has generated a great deal of excitement. Scientists have found adult stem cells in many more tissues than they once thought possible. This finding has led researchers and clinicians to ask whether adult stem cells could be used for transplants. In fact, adult hematopoetic, or blood-forming, stem cells from bone marrow have been in used in transplants for 40 years. Scientists now have evidence that stem cells exist in the brain and in the heart. If the differentiation of adult stem cells can be controlled in the laboratory, these cells may become the basis of transplantation-based therapies.

STEM CELL part 26

What are adult stem cells?

An adult stem cells is though to be an undifferentiated cell, found among differentiated cells in a tissue or organ that can renew itself and can differentiate to yield some or all of the major specialized cell types of the tissue or organ. The primary roles of adult stem cells in a living organism are to maintain and repair the tissue in which they are found. Scientists also use the term somatic stem cell instead of adult stem cell, where somatic refers to cells of the body (not the germ cells, sperm or eggs). Unlike embryonic stem cells, which are defined by their origin (cells from the preimplantation-stage embryo), the origin of adult stem cells in some mature tissues is still under investigation.

STEM CELL part 25

If scientists can reliably 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, traumatic spinal cord injury, Duchenne's muscular dystrophy, heart disease and vision and hearing loss.

STEM CELL part 24

So, to generate cultures of specific types of differentiated cells-heart muscle cells, blood cells, or nerve cells, for example-scientists try to control the differentiation of embryonic stem cells. They change  the chemical composition of the culture medium, alter the surface of the culture dish, or modify 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.

STEM CELL part 23

How are embryonic stem cells stimulated to differentiate?

As long as the embryonic stem cells in culture are grown under appropriate conditions, they can remain undifferentiated (unspecialized). But if cells are allowed to clump together to form embryoid bodies, they begin to differentiate spontaneously. They can form muscle cells, nerve cells, and many other cell types. Although spontaneous differentiation is a good indicator that a culture of embryonic stem cells is healthy, the process is uncontrolled and therefore an inefficient strategy to produce cultures of specific cell types.

STEM CELL part 22

Testing whether the human embryonic stem cells are pluripotent by:

• Allowing the cells to differentiate spontaneously in cell culture
• Manipulating the cells so they will differentiate to form cells characteristics of the three germ layers
• Injecting the cells into a mouse with a suppressed immune system to test for the formation of benign tumour called a teratoma. Since the mouse's immune system is suppressed, the injected human stem cells are not rejected by the mouse immune system and scientists can observe growth and differentiation of the human stem cells. Teratomas typically contain  a mixture of many differentiated or partly differentiated cell types-an indication that the embryonic stem cells are capable of differentiating into multiple cell types.

STEM CELL part 21

Scientists who study human embryonic stem cells have not yet agreed on a standard battery of tests that measure the cells' fundamental properties. However, laboratories that grow human embryonic stem cell lines use several kinds of tests, including:

• Growing and subculturing stem cells for many months. This ensures that the cells are capable of long-term growth and self-renewal. Scientists inspect the cultures through a microscope to see that the cells look healthy and remain undifferentiated,
• Using specific techniques to determine the presence of transcription factors that are typically produced by undifferentiated cells. Two of the most important transcription factors are Nanog and Oct4. Transcription factors helps turn genes on and off at the right time, which is an important of cell differentiation and embryonic development. In this case, both Oct4 and Nanog are associated with maintaining the stem cells in an undifferentiated state, capable of self-renewal.
• Using specific techniques to determine the presence of particular cell surface markers that are typically produced by undifferentiated cells.
• Examining the chromosomes under a microscope. This is a method to assess whether the chromosomes are damaged or if the number of chromosomes has changed. It does not detect genetic mutations in the cells.
• Determining whether the cells can be re-grown, or subcultured, after freezing, thawing and re-plating

STEM CELL part 20

What laboratory tests are used to identify embryonic stem cells?

At various points during the process of generating embryonic stem cell lines, scientists test the cells to see whether they exhibit the fundamental properties that make them embryonic stem cells. This process called characterization.

STEM CELL part 19

The process of generating an embryonic stem cell line is somewhat inefficient, so lines are not produced each time cells from the preimplantation-stage embryo are placed into a culture dish. However, if the plated cells survive, divide and multiply enough to crowd the dish, they are removed gently and plated into several fresh culture dishes. The process of re-plating or subculturing the cells is repeated many times and for many months. Each cycle of subculturing the cells is referred to as a passage. Once the cell lines is established, the original cells yield millions of embryonic stem cells. Embryonic stem cells that have proliferated in cell culture for six or more months without differentiating, are pluripotent, and appear genetically normal are referred to as an embryonic stem cell line. At any stage, in the process, batches of cells can be frozen and shipped to other laboratories for further culture and experimentation.

STEM CELL part 18

How are embryonic stem cells grown in the laboratory?

Growing cells in the laboratory is known as cell culture. Human embryonic stem cells (hESCs) are generated by transferring cells from a preimplantation-stage embryo into a plastic laboratory culture dish that contains a nutrient broth known as culture medium. The cells divide and spread over the surface of the dish. The inner surface of the culture dish is typically coated with mouse embryonic skin cells that have been treated so they will not divide. This coating layer of cells is called a feeder layer. The mouse cells in the bottom of the culture dish provide the cells a sticky surface to which they can attach. Also, the feeder cells release nutrients into the culture medium. Researchers have  devised ways to grow embryonic stem cells without mouse feeder cells. This is a significant scientific advance because of the risk that viruses or other macromolecules in the mouse cells may be transmitted to the human cells.

STEM CELL part 17

WHAT ARE EMBRYONIC STEM CELLS?

What stages of early embryonic development are important for generating embryonic stem cells?

Embryonic stem cells, as their name suggests, are derived from embryos. Most embryonic stem cells are derived from embryos that develop eggs that have been fertilized in vitro-in an in vitro fertilization clinic-and then donated for research purposes with informed consent of the donors. They are not derived from eggs fertilized in a woman's body.

STEM CELL part 16

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 normally gives rise to the many types of blood cells. It is generally accepted that a blood-forming cell in the bone marrow-which is called a hematopoetic stem cell-cannot give rise to the cells of a very different tissue, such as nerve cells in the brain. Experiment over the last several years have purported to show that stem cells  from one tissue may give rise to cell types of a completely different tissue. This remains an  area of great debate within the research community. This controversy demonstrates the challenges of studying adult stem cells and suggests that  additional research using adult stem cells is necessary to understand their full potential as future therapies.

STEM CELL part 15

Many questions about stem cell differentiation remain. For example, are the internal and external signals for cell differentiation similar for all kinds of stem cells? Can specific sets of signals can be identified that promote differentiation into specific cell types? Addressing these questions may lead scientists to find new ways  to control stem cell differentiation in the laboratory, thereby growing cells or tissues that can be used for specific purposes such as cell-based therapies or drug screening.

STEM CELL part 14

Stem cells can give rise to specialized cells. When unspecialized stem cells give rise to specialized cells, the process is called differentiation. While differentiating, the cell usually goes through several stages, becoming more specialized at each step. Scientists are just beginning to understand the signal inside and outside cells that trigger each step 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. The external signals for cell differentiation include chemicals secreted by other cells, physical contact with neighboring cells, and certain molecules in the microenvironment. The interaction of signals during differentiation causes the cell's DNA to acquire epigenetic marks that restrict DNA expression in the cell and can be passed on through cell division.

STEM CELL part 13

Stem cells are unspecialized. One of the fundamental properties of a stem cell is that it does not have any tissue-specific structures that allow it to perform specialized functions.  For example, a stem cell cannot work with its neighbors to pump blood through the body (like a heart muscle cell), and it cannot carry oxygen molecules through the blood stream (like a red blood cell). However, unspecialized stem cells can give rise to specialized cells, including heart muscle cells, blood cells, or nerve cells.

STEM CELL part 12

The specific factors and conditions that allow stem cells to remain unspecialized are of great interest to scientists. It has taken many years of trial and error to learn to derive  and maintain stem cells in the laboratory without them spontaneously differentiating into specific cell types. For example, it took two decades to learn how to grow human embryonic stem cells in the laboratory following the development of conditions for growing mouse stem cells. Likewise, scientists must first understand the signals that enable a non embryonic (adult) stem cells population to proliferate and remain unspecialized before they will be able to grow large numbers of unspecialized adult stem cells in the laboratory.

STEM CELL part 11

Discovering the answers to these questions may make it possible to understand how cell proliferation is regulated during normal embryonic development or during  the abnormal cell division that leads to cancer. Such information would also enable scientists to grow embryonic and non-embryonic stem cells more efficiently in the laboratory.

STEM CELL part 10

Scientists are trying to understand two fundamental properties of stem cells that relate to their long-term self-renewal:

• Why can embryonic stem cells proliferate for a year or more in the laboratory without differentiating, but most non-embryonic stem cells (adult stem cells) cannot.
• What factors in living organisms normally regulate stem cell proliferation and self-renewal?

STEM CELL part 9

Stem cells are capable of dividing and renewing themselves for long periods. Unlike muscle cells, blood cells, or nerve cells-which do not normally replicate themselves-stem cells may replicate many times, proliferate. A starting population of stem cells that proliferates for many months in the laboratory can yield millions of cells. If the resulting cells continue to be unspecialized, like the parent stem cells, the cells are said to be capable of long-term self-renewal.

STEM CELL part 8

WHAT ARE THE UNIQUE PROPERTIES OF ALL STEM CELLS?

Stem cells differ from other types of cells in the body. All stem cells-regardless of their source-have three general properties:

• they are capable of dividing and renewing themselves for long periods
• they are unspecialized
• they can give rise to specialized cell types

STEM CELL part 7

Research on stem cells continues to advance knowledge about how an organism develops from a single cell and how healthy cells replace damaged cells in adult organisms. Stem cell research is one of the most fascinating areas of contemprary biology, but, as with many expanding fields of scientific inquiry, research on stem cells raises scientific questions as rapidly as it generates new discoveries.

STEM CELL part 6

Laboratory studies of stem cells enable scientists to learn about the cells essential properties and what makes them different from specialized cell types. Scientists are already using stem cells in the laboratory to screen new drugs and to develop model systems to study normal growth and identify the causes of birth defects.

STEM CELL part 5

Given their unique regenerative abilities, stem cells offer new potentials for treating diseases such as diabetes and heart disease. However, much work remains to be done in the laboratory and the clinic to understand how to use these cells for cell-based therapies to treat disease, which is also referred to as regenerative or reparative medicine.

STEM CELL part 4

Stem cells are important for living organisms for many reasons. In the 3- to 5-day-old embryo, called a blastocyst, the inner cells give rise to the entire body of the organism, including all of the many specialized cell types and organs such as the heart, lung, skin, sperm, eggs and other tissues. In some adult tissues, such as bone marrow, muscle, and brain, discrete populations of adult stem cells generate replacements for cells that are lost through normal wear and tear, injury, or disease.

STEM CELL part 3

Until recently, scientists primarily worked with two kinds of stem cells from animals and humans: embryonic stem cells and non-embryonic "somatic" or "adult" stem cells. Scientists discovered ways to derive embryonic stem cells from early mouse embryos in 1981. The detailed study of the biology of mouse stem cells led to the discovery, in 1998, of  a method to derive stem cells  from human embryos and grow the cells in the laboratory. These cells are called human embryonic stem cells. The embryos used in these studies were created for reproductive purposes through 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, researchers made another breakthrough by identifying conditions that would allow some specialized adult cells to be "reprogrammed" genetically to assume a stem-cell like state. This new type of stem cell, called induced pluripotent stem cells.

STEM CELL part 2

Stem cells are distinguished from other type cell types by two important characteristics. First, they are unspecialized cells capable of renewing themselves through cell division, sometimes after long periods of inactivity. Second, under certain physiologic or experimental conditions, they can be induced to become tissue- or organ-specific cells with special functions. In some organs, such as the gut and bone marrow, stem cells regularly divide to repair and replace worn out or damaged tissues. In other organs, however, such as the pancreas and the heart, stem cells only divide under special conditions.

STEM CELL part 1

WHAT ARE STEM CELLS, AND WHY ARE THEY IMPORTANT?

Stem cells have the remarkable potential to develop into many different cell types in the body during early life and growth. In addition, in many tissues they serve as a sort of internal repair system, dividing essentially without limit to replenish other cells as long as the person or animal is still alive, When stem cell divides, each new cell has the potential either to remain a stem cell or become another type of cell with a more specialized function, such as a muscle cell, a red blood cell, or a brain cell.

Immunological aspects of allergy and anaphylaxis part 63

Testing for contact dermatitis involves placing a patch of the suspected substance or substances on the back. The area must be kept clean and dry for forty-eight hours, after which the various patches are removed, and the individual areas are evaluated for inflammatory responses. A positive response then  characterizes  a type IV reaction, and avoidance of the offending allergen is the treatment of choice. Thirty milligrams per day of systemic steroids may be required when large areas of the skin are involved (>25 percent of body surface). Otherwise, corticosteroid creams may employed; however, avoidance of the contactant is most crucial.

Immunological aspects of allergy and anaphylaxis part 62

Although most people exposed to these presenting allergens do not develop contact dermatitis, certain substances such as dinitrochlorobenzene may sensitize as many as 90 percent of normal individuals, which is why the patient's history with suspected contact dermatitis is important. Among those situations patients need to elucidate are occupation, cosmetics, topical or systemic drugs, recreational activities, effects of holidays, and time course.

Immunological aspects of allergy and anaphylaxis part 61

CONTACT DERMATITIS

Classical contact dermatitis is a Gell and Coombs type IV reaction, mediated by previously sensitized lymphocytes, which is exhibited by raised, very pruritic rash at the sight of the contact. Unlike allergic reactions of a type I, IgE-mediated contact dermatitis,  as a type IV reaction, involving-molecular-weight allergens (less  than 1 kDa). These contact allergens are haptens and need to link with proteins in the skin to become allergenic. These haptens may be readily absorbed into the skin, a reactions that renders them antigenic. If the skin is exposed to humidity or warmth, the penetration of the hapten is greater, and the chance of developing contact dermatitis is greater. As these haptens make their way into extravascular spaces, they combine with serum proteins or cell membranes  of antigen-presenting cells. The processed antigens is presented by Langerhans cells to T cells leading to a cascade of events that result in an influx of mononuclear cells into the dermis and epidermis, hence dermatitis.

Immunological aspects of allergy and anaphylaxis part 60

Topical mast cell stabilizers may be used for atopic keratokonjunctivitis, but often topical corticosteroids are required. Facial eczema must be controlled, and lid margins must be treated. Conventional treatment for seasonal or perennial allergic conjunctivitis is not sufficient. Atopic keratokonjunctivitis may be difficult to manage.

Immunological aspects of allergy and anaphylaxis part 59

Atopic keratoconjunctivitis is a rare, lifelong problem, seen more commonly in adults with atopic disease such as atopic dermatitis. This facial eczema usually involves eyelids, and the lid margins usually show chronic inflammation of the lash follicles (blepharitis) and stapylococcal organisms. In addition, the lid margins may thicken and keratonize, and the lids may turn out or turn in. Corneal plaques, cataracts, and defects of the corneal epithelial may lead to loss of sight.

Immunological aspects of allergy and anaphylaxis part 58

Atopic Keratoconjunctivitis

Conjunctivitis is an inflammation of the conjunctiva, the inner eyelids surfaces and the mucous membrane lining the sclera. When the cause is seasonal or perennial (very common), the etiology may be pollen, animals or dust mites. Prevalence is common, and the treatment usually involves mast cell inhibitors and topical and systemic antihistamines. Topical opthalmic steroids are usually avoided.

Immunological aspects of allergy and anaphylaxis part 57

The effects of the weather, including temperature and humidity, on eczema add to these immunological and non immunological factors. A day at the beach  may have a positive effect on atopic dermatitis, while a dry, cold winter  has the opposite effect. Wet wraps are beneficial because they replace the skin's moisture loss. Corticosteroid creams, hydrotic creams and ointments, and occasional oral antibiotics are the main-stays  of treatment. Avoiding allergens, local skin care, and treatment of the pruritis are the best approaches for treating atopic eczema.

Immunological aspects of allergy and anaphylaxis part 56

Although those with atopic eczema often test positive to various foods and house dust mites, strict avoidance of these allergens does not improve the problem. Although allergies are an important component in atopic eczema, an estimated 90% of patients with moderate to severe eczema have staphylococcal infection of the skin. This condition and large insensible water loss make atopic eczema a difficult medical problem.