What are the similarities and differences between embryonic and adult stem cells?

Human embryonic and adult stem cells each have advantages and disadvantages regarding potential use for cell-based regenerative therapies. Of course, adult and embryonic stem cells differ in the number and type of differentiated cells types they can become. Embryonic stem cells can become all cell types of the body because they are pluripotent. Adult stem cells are generally limited to differentiating into different cell types of their tissue of origin. However, some evidence suggests that adult stem cell plasticity may exist, increasing the number of cell types a given adult stem cell can become.

Large numbers of embryonic stem cells can be relatively easily grown in culture, while adult stem cells are rare in mature tissues and methods for expanding their numbers in cell culture have not yet been worked out. This is an important distinction, as large numbers of cells are needed for stem cell replacement therapies.

A potential advantage of using stem cells from an adult is that the patient's own cells could be expanded in culture and then reintroduced into the patient. The use of the patient's own adult stem cells would mean that the cells would not be rejected by the immune system. This represents a significant advantage as immune rejection is a difficult problem that can only be circumvented with immunosuppressive drugs.

Embryonic stem cells from a donor introduced into a patient could cause transplant rejection. However, whether the recipient would reject donor embryonic stem cells has not been determined in human experiments.

http://stemcells.nih.gov/info/basics/basics5.asp

What are the key questions about adult stem cells?

Many important questions about adult stem cells remain to be answered. They include:

• How many kinds of adult stem cells exist, and in which tissues do they exist?
• What are the sources of adult stem cells in the body? Are they "leftover" embryonic stem cells, or do they arise in some other way? Why do they remain in an undifferentiated state when all the cells around them have differentiated?
• Do adult stem cells normally exhibit plasticity, or do they only transdifferentiate when scientists manipulate them experimentally? What are the signals that regulate the proliferation and differentiation of stem cells that demonstrate plasticity?
• Is it possible to manipulate adult stem cells to enhance their proliferation so that sufficient tissue for transplants can be produced?
• Does a single type of stem cell exist—possibly in the bone marrow or circulating in the blood—that can generate the cells of any organ or tissue?
• What are the factors that stimulate stem cells to relocate to sites of injury or damage?

http://stemcells.nih.gov/info/basics/basics4.asp

What is known about adult stem cell differentiation?

Hematopoietic and stromal stem cell differentiation

As indicated above, 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. Adult stem cells may also exhibit the ability to form specialized cell types of other tissues, which is known as transdifferentiation or plasticity.

Normal differentiation pathways of adult stem cells. In a living animal, adult stem cells can divide for a long period 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 (Figure 2).

• Hematopoietic stem cells give rise to all the types of blood cells: red blood cells, B lymphocytes, T lymphocytes, natural killer cells, neutrophils, basophils, eosinophils, monocytes, macrophages, and platelets.
• Bone marrow stromal cells (mesenchymal stem cells) give rise to a variety of cell types: bone cells (osteocytes), cartilage cells (chondrocytes), fat cells (adipocytes), and other kinds of connective tissue cells such as those in tendons.
• 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.
• 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.
• 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.

Adult stem cell plasticity and transdifferentiation. A number of experiments have suggested that certain adult stem cell types are pluripotent. This ability to differentiate into multiple cell types is called plasticity or transdifferentiation. The following list offers examples of adult stem cell plasticity that have been reported during the past few years.

• Hematopoietic stem cells may differentiate into: three major types of brain cells (neurons, oligodendrocytes, and astrocytes); skeletal muscle cells; cardiac muscle cells; and liver cells.
• Bone marrow stromal cells may differentiate into: cardiac muscle cells and skeletal muscle cells.
• Brain stem cells may differentiate into: blood cells and skeletal muscle cells.

Current research is aimed at determining the mechanisms that underlie adult stem cell plasticity. If such mechanisms can be identified and controlled, existing stem cells from a healthy tissue might be induced to repopulate and repair a diseased tissue

http://stemcells.nih.gov/info/basics/basics4.asp

What tests are used for identifying adult stem cells?

Scientists do not agree on the criteria that should be used to identify and test adult stem cells. However, they often use one or more of the following three methods: (1) labeling the cells in a living tissue with molecular markers and then determining the specialized cell types they generate; (2) removing the cells from a living animal, labeling them in cell culture, and transplanting them back into another animal to determine whether the cells repopulate their tissue of origin; and (3) isolating the cells, growing them in cell culture, and manipulating them, often by adding growth factors or introducing new genes, to determine what differentiated cells types they can become.

Also, a single adult stem cell should be able to generate a line of genetically identical cells—known as a clone—which then gives rise to all the appropriate differentiated cell types of the tissue. Scientists tend to show either that a stem cell can give rise to a clone of cells in cell culture, or that a purified population of candidate stem cells can repopulate the tissue after transplant into an animal. Recently, by infecting adult stem cells with a virus that gives a unique identifier to each individual cell, scientists have been able to demonstrate that individual adult stem cell clones have the ability to repopulate injured tissues in a living animal.

http://stemcells.nih.gov/info/basics/basics4.asp

Scientists uncover the potential to control adult stem cells

Research being presented today (10 April) at the UK National Stem Cell Network Annual Science Meeting in Edinburgh represents a step towards the use of Adult Stem Cells (ASCs) to repair damaged tissue. Speaking at the conference in Edinburgh, Professor Cay Kielty of the University of Manchester describes how she and her team have uncovered a messaging system that instructs ASCs to contribute to tissue repair in response to chemical signals in the body. This work, funded by the Medical Research Council, holds great hope for the development of techniques by which ASCs could be instructed to repair damaged tissues.

ASCs have potential for therapeutic use and avoid many of the ethical issues associated with embryonic stem cells. However, at present it is necessary to gain a better understanding of how, from first principles, ASCs can be controlled based on signalling systems that normally give instructions within the body. There is the potential in the future to apply such understanding to the generation of cells for transplant.

Professor Kielty’s team study stem cells that are found in human bone marrow called mesenchymal stem cells (MSCs). MSCs have the ability to relocate and develop into several different types of cells and tissue and are very promising as a source of cells for transplant in tissue repair. As well as offering the potential for bespoke treatments derived from a person’s own cells, MSCs are unlikely to trigger a severe immune response, and may be suitable for “off-the-shelf” treatments for tissue repair. This research focuses on the details of a messaging system that leads to the development of blood vessels from MSCs in the body. This system is called ‘PDGF receptor signalling’.

In PDGF receptor signalling, receptors on the surface of the MSCs receive messages in the form of molecules that are involved in directing human growth and development – ‘growth factors’. It has been found that there is a complex messaging system that relays and coordinates the signals from certain growth factors to the MSCs, which encourage their recruitment to new blood vessels. This involves cooperation between two types of receptor called ‘PDGF receptor’ and ‘neuropilin-1’ that respond to growth factors called PDGF and VEGF-A arriving at the cell surface, as well as sensing close proximity to other cells that make up the blood vessel.

As well as offering insights into the use of ASCs for tissue repair therapies, a better knowledge of how blood vessels develop is crucial to understanding and treating a huge range of diseases such as cancer, diabetic retinopathy and cardiovascular disease.

Professor Kielty said: “What we have shown is that adult stem cells respond in particular ways to some of the chemical signals in the body. The next stage will be to understand how this messaging system regulates relocation of the MSCs and instructs them to become blood vessel cells. After that, we can look at applying our understanding to develop stem-cell derived therapies for tissue repair.”

http://www.eurekalert.org/pub_releases/2008-04/babs-sut040808.php

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

adult stem cells have been identified in many organs and tissues. One important point to understand about adult stem cells is that there are a very small number of stem cells in each tissue. Stem cells are thought to reside in a specific area of each tissue where they may remain quiescent (non-dividing) for many years until they are activated by disease or tissue injury. The adult tissues reported to contain stem cells include brain, bone marrow, peripheral blood, blood vessels, skeletal muscle, skin and liver.

Scientists in many laboratories are trying to find ways to grow adult stem cells in cell culture and manipulate them to generate specific cell types so they can be used to treat injury or disease. Some examples of potential treatments include replacing the dopamine-producing cells in the brains of Parkinson's patients, developing insulin-producing cells for type I diabetes and repairing damaged heart muscle following a heart attack with cardiac muscle cells.

http://stemcells.nih.gov/info/basics/basics4.asp

What are adult stem cells?

An adult stem cell is an undifferentiated cell found among differentiated cells in a tissue or organ, can renew itself, and can differentiate to yield 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. Some scientists now use the term somatic stem cell instead of adult stem cell. Unlike embryonic stem cells, which are defined by their origin (the inner cell mass of the blastocyst), the origin of adult stem cells in mature tissues is unknown.

Research on adult stem cells has recently 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 scientists to ask whether adult stem cells could be used for transplants. In fact, adult blood forming stem cells from bone marrow have been used in transplants for 30 years. Certain kinds of adult stem cells seem to have the ability to differentiate into a number of different cell types, given the right conditions. If this differentiation of adult stem cells can be controlled in the laboratory, these cells may become the basis of therapies for many serious common diseases.

The history of research on adult stem cells began about 40 years ago. In the 1960s, 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 cells, was discovered a few years later. Stromal cells are a mixed cell population that generates bone, cartilage, fat, and fibrous connective tissue.

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

http://stemcells.nih.gov/info/basics/basics4.asp

Adult stem cells

Main article: Adult stem cell

Stem cell division and differentiation. A - stem cell; B - progenitor cell; C - differentiated cell; 1 - symmetric stem cell division; 2 - asymmetric stem cell division; 3 - progenitor division; 4 - terminal differentiation

The term adult stem cell refers to any cell which is found in a developed organism that has two properties: the ability to divide and create another cell like itself and also divide and create a cell more differentiated than itself. Also known as somatic (from Greek Σωματικóς, "of the body") stem cells and germline (giving rise to gametes) stem cells, they can be found in children, as well as adults.^[13] Pluripotent adult stem cells are rare and generally small in number but can be found in a number of tissues including umbilical cord blood.^[14] Most adult stem cells are lineage-restricted (multipotent) and are generally referred to by their tissue origin (mesenchymal stem cell, adipose-derived stem cell, endothelial stem cell, etc.).^[15][16]

A great deal of adult stem cell research has focused on clarifying their capacity to divide or self-renew indefinitely and their differentiation potential.^[17] In mice, pluripotent stem cells are directly generated from adult fibroblast cultures.^[18]

While embryonic stem cell potential remains untested, adult stem cell treatments have been used for many years to treat successfully leukemia and related bone/blood cancers through bone marrow transplants.^[19] The use of adult stem cells in research and therapy is not as controversial as embryonic stem cells, because the production of adult stem cells does not require the destruction of an embryo. Consequently, more US government funding is being provided for adult stem cell research.

http://en.wikipedia.org/wiki/Stem_cell

The future of stem cells

Expect rapid progress in adult stem cells and slower, less intense work with embryonic stem cells. Embryonic stem cell technology is already looking rather last-century, along with therapeutic cloning. History will show that by 2020 we were already able to produce a wide range of tissues using adult stem cells, with spectacular progress in tissue building and repair. In some cases these stem cells will be actually incorporated into the new repairs as differentiated cells, in other cases, they will be temporary assistants in local repair processes.

We will also see some exciting new pharmaceutical products in the pipeline, which promise to do some of the same tricks without having to remove a single stem cell from the body. These drugs may for example activate bone marrow cells and encourage them to migrate to parts of the body where repairs are needed.

And along the way we will see a number of biotech companies fold, as a result of over-investment into embryonic stem cells, plus angst over ethics and image, without watching the radar screen closely enough, failing to see the onward march of adult stem cell technology.

Using embryos as a source of spare-part cells will always be far more controversial than using adult tissue, or perhaps cells from umbilical cord after birth, and investors will wish to reduce uneccessary risk, both to the projects they fund, and to their own organisations by association.

Despite this, we can expect embryonic stem cell research to continue in some countries, with the hope of scientific breakthroughs of various kinds.

http://www.globalchange.com/stemcells2.htm

Germany relaxs limits on stem cell research

Germany has decided to ease restrictions on stem cell research to ensure its scientists stay ahead of the pack.

The Bundestag lower house of parliament has approved new measures amid fears the country's top scientists would move abroad if rules remained too restrictive.

Under the bill, researchers will now be able to import stem cells created before the first of May 2007, rather than only use cells existing before 2002.

But the new limits were only passed after an emotionally charged debate.

Technology and Research Minister, Annette Schavan, stressed that scientists would be able to extract stem cells out of embryos that are not destined for a pregnancy.

She also said that Germany had to ensure its scientists could keep up globally.

Many of those who believe that life begins at conception argued that cells should be harvested from adults, not embryos.

German lawmakers also voted against two more radical proposals - one calling for a ban on all embryonic stem cell research, the other suggesting the cut-off date be scrapped entirely.

http://www.euronews.net/index.php?page=info&article=480239&lng=1

What are stem cells - embryonic and adult stem cells

Stem cells are relatively primitive cells that have the ability to divide rapidly to produce more specialized cells. Stem cells in the embryo are capable of huge variation in the kinds of tissues they make, reproduce rapidly and have attracted interest of researchers for decades. However embryonic stem cells are hard to get hold of in humans - you need a supply of human embryos, which requires either breaking the law in some countries or applying for complex licenses in others.

Embryonic stem cells are also hard to control, and hard to grow in a reliable way. They have "minds" of their own, and embryonic stem cells are often unstable, producing unexpected results as they divide, or even cancerous growths. Human embryonic stem cells usually cause an immune reaction when transplanted into people, which means cells used in treatment may be rapidly destroyed unless they are protected, perhaps by giving medication to suppress the immune system (which carries risks).

One reason for intense interest in human cloning technology is so-called therapeutic cloning. This involves combining an adult human cell with a human egg from which the nucleus has been removed. The result is a human embryo which is dividing rapidly to try and become an identical twin of the cloned adult. If implanted in the womb, such cloned embryos have the potential to be born normally as cloned babies, although there are many problems to overcome, including catastrophic malformations and premature ageing as seen in animals such as Dolly the sheep.

In theory, therapeutic cloning could allow scientists to take embryonic stem cells from the cloned embryo, throw the rest of the embryo away and use the stem cells to generate new tissue which is genetically identical to the person cloned. In practice this is a very expensive approach fraught with technical challenges as well as ethical questions and legal challenges.

An alternative is to try to create a vast tissue bank of tens of thousands of embryonic cells lines, by extracting stem cells from so many different human embryos that whoever needs treatment can be closely matched with the tissue type of an existing cell line. But even if this is achieved, problems of control and cancer remain. And again there are many ethical considerations with any science that uses human embryos, each of which is an early developing but complete potential human being, which is why so many countries have banned this work.

http://www.globalchange.com/stemcells2.htm