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Friday, August 31, 2007

Stem Cells from Adult Bone Marrow Converted to Brain Cells

steam cell

Stem cells from human adult bone marrow have been successfully converted into functional brain cells, putting science closer to the possibility that one day damaged brain tissue can be repaired by implanting new cells. Not only that, it also means that people could potentially become their own donors, circumventing ethical issues related to other, more controversial sources of stem cells.

Dr. Alexander Storch, professor of neurodegenerative diseases at the Technical University in Dresden, Germany, described the research at the annual meeting of the American Academy of Neurology here.

Stem cells are non-specialized cells that can divide and turn into other specialized cells such as bone, brain or blood cells. While large numbers of stem cells are present in developing embryos, smaller quantities of stem cells occur in certain parts of the adult body, such as in the bone marrow. It is believed stem cells in mature animals are there to help with tissue repair.

Stem cells in adult human bone marrow are normally able to change, or differentiate, into one of three cell types: cartilage, fat cells or bone cells, Dr. Storch said. However, researchers in various laboratories around the world have been working with stem cells derived from adult human bone marrow to try to change them into other types of cells, such as nerve cells.

Some small amount of success was achieved in those laboratories, though these other research teams attempted to convert bone marrow stem cells directly into glial and neuron cells, types of nerve cells found in the brain. The resulting cells were not functional, and would not be of sufficient quality for transplantation. Dr. Storch's team added another step and have had more success.

What researchers in Dr. Storch's laboratory did was to alter the way bone marrow stem cells are grown in culture. Instead of trying to turn them directly into glial and neuronal cells, the researchers instead turned the bone marrow stem cells into another type of stem cell -- neural stem cells. To do this, they altered the environment in the culture by using a medium that is usually used for culturing neural stem cells. They then added growth factors. Once the bone marrow cells stayed in the mixture for a while, they turned into neural stem cells, also referred to as neuroprogenitor cells.

"We do not produce nerve cells or glial cells, but immature neuroprogenitors," Dr. Storch said. The hope is that these could be transplanted straight into the brain where they would, in theory, turn into fully functional glia and neuron cells.

There is already evidence that these neural stem cells are active and will turn into the appropriate glial and neuron cells is transplanted into a brain. Researchers found that while in suspension, the cells grow into neurospheres (small balls or aggregates of precursor brain cells) and that they expressed, or produced, the neural stem cell marker nestin. Both of these features were missing in previous attempts by researchers in other laboratories.

"Our protocol generated a high yield of cells," Dr. Storch said. Plus, the cells grew quickly. "We calculate we'd need approximately 70 days to grow enough cells for a transplant procedure from one bone marrow biopsy. We'd have the same quantity of cells usually transplanted in studies of Parkinson's Disease," he said.

Scientists hope that the research may one day help treat diseases such as Parkinson's and Alzheimer Disease, and Multiple Sclerosis, all diseases where nerve or brain tissue is damaged.

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StemStem Cell Basics

Stem cells have the remarkable potential to develop into many different cell types in the body. Serving as a sort of repair system for the body, they can theoretically divide without limit to replenish other cells as long as the person or animal is still alive. When a stem cell divides, each new cell has the potential to either 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.

This document covers basic information about stem cells. For a more detailed discussion, see our Stem Cell Reports. Or you can check the Frequently Asked Questions page for quick answers to specific queries.

Throughout Stem Cell Basics, the first reference to a Glossary term on a page appears in bold, underlined maroon type. Clicking on the term will open its definition from the Glossary page in a new window.

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.

A. 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.

B. 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.

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