Researchers produce cells they say are identical to embryonic stem cells
Los Angeles Times, July 23, 2009

Two groups of Chinese researchers induced cells from connective tissue in mice to revert back to their
embryonic state and producing living mice from them.

Researchers first produced this new type of cell, called induced pluripotent stem, or iPS, cells, two years
ago, but there have been lingering doubts about whether the cells are truly identical to embryonic cells
or instead are capable of producing only some types of body cells.

The study was led Qi Zhou at the Chinese Academy of Sciences's State Key Laboratory of Reproductive
Biology, the team created iPS cells, using mouse fibroblasts, which are cells found in connective tissue
in the skin.

More recently, researchers have fused the cells of the host blastocyst so that each cell contains double
the number of chromosomes, making them tetraploid. When that is done, the host cells can form only
the placental tissues; all the animal's tissues must come from the injected iPS cells.
What are stem cells?
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 a
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.

Stem cells are distinguished from other 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.

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. The functions and
characteristics of these cells will be explained in this document. Scientists discovered ways to derive
embryonic stem cells from early mouse embryos nearly 30 years ago, 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 is called
induced pluripotent stem cells

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.

Why stem cell studies are so important?
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
regenerative or reparative medicine.

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.

For example, it may become possible to generate healthy heart muscle cells in the laboratory and then
transplant those cells into patients with chronic heart disease. Preliminary research in mice and other
animals indicates that bone marrow stromal cells, transplanted into a damaged heart, can have
beneficial effects. Whether these cells can generate heart muscle cells or stimulate the growth of new
blood vessels that repopulate the heart tissue, or help via some other mechanism is actively under
investigation. For example, injected cells may accomplish repair by secreting growth factors, rather
than actually incorporating into the heart.

What are the unique properties of all stem cells?
Stem cells differ from other kinds of cells in the body. All stem cells—regardless of their source—have
three general properties: [1] they are capable of dividing and renewing themselves for long periods; [2]
they are unspecialized; [3] and they can give rise to specialized cell types.

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,
or 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 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 bloodstream (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 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
signals inside and outside cells that trigger each stem 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.

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 hematopoietic
stem cell—cannot give rise to the cells of a very different tissue, such as nerve cells in the brain.

What are induced pluripotent stem cells?
Induced pluripotent stem cells (iPSCs) are adult cells that have been genetically reprogrammed to an
embryonic stem cell–like state by being forced to express genes and factors important for maintaining
the defining properties of embryonic stem cells. Although these cells meet the defining criteria for
pluripotent stem cells, it is not known if iPSCs and embryonic stem cells differ in clinically significant
ways. Mouse iPSCs were first reported in 2006, and human iPSCs were first reported in late 2007.
Mouse iPSCs demonstrate important characteristics of pluripotent stem cells, including expressing stem
cell markers, forming tumors containing cells from all three germ layers, and being able to contribute to
many different tissues when injected into mouse embryos at a very early stage in development. Human
iPSCs also express stem cell markers and are capable of generating cells characteristic of all three
germ layers.

SOURCE NIH Website July 009
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