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Posts Tagged ‘clinical trials’

Stem Cells Discovered in Menstrual Blood: Endometrial Regenerative Stem Cells

March 27th, 2009

Often the feasibility of using stem cells for regenerative therapies is limited by two factors: obtaining a significant number of cells and doing so in a relatively noninvasive manner. Because our bodies freely shed a limited and select number of cells, many stem cell types must be obtained using a rather invasive procedure. However, around the beginning of last year two laboratories independently reported the discovery of a new type of stem cell that may overcome both obstacles; stem cells were found to reside in menstrual blood (Meng et al., 2007; Patel et al., 2008). These stem cells, termed endometrial regenerative cells (ERCs), are not only harvested in a noninvasive manner and relatively readily available in large quantities, but they potentially overcome the problem of immune rejection in many female patients as well.

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The uterus is lined by a layer of cells called the endometrium. During the menstrual cycle, the endometrium cycles between thickening and being broken down if fertilization does not occur. The break down and expulsion of the endometrium is called menstruation, or menstrual bleeding, and is the source of endometrial regenerative cells (ERCs).

Researchers suspected stem cells to be present in menstrual blood because stem cells were previously found to be present in the lining of the uterus. The wall of the uterus is lined by a layer of cells called the endometrium (see figure). To create ideal conditions for the uterus to accept and nurture an embryo, the endometrium lining becomes thicker and increases the number of blood vessels and glands within it. However, if implantation does not occur, the endometrium lining is broken down and shed. Overall, the endometrium is quite a hyperproliferative tissue, continuously being broken down and rebuilt; it is an ideal tissue to investigate for the presence of stem cells. In the menstrual cycle, the shedding is known as menstruation, or menstrual bleeding; the excreted menstrual blood is made up of blood as well as cells from the endometrium layer. Researchers previously reported the presence of stem cells in the intact endometrium lining of the uterus (Cho et al., 2004; Schwab et al., 2005; Du and Taylor, 2007). Because stem cells were found in the endometrium, researchers thought it likely that stem cells could also be found in the shed endometrium in the form of menstrual blood, which can be obtained in relatively large quantities in a much less invasive manner. However, the stem cells discovered in menstrual blood, ERCs, appear to be rather different from stem cells derived from the intact endometrium.

While stem cells from the intact endometrium appear to be mesenchymal stem cells (MSCs, as discussed earlier), ERCs do not; they are distinctly different not only in their undifferentiated state, but in the cells they can differentiate into as well. Researchers categorize stem cells into certain groups based off of, among other factors, their cell morphology and the proteins they express. An established stem cell group usually expresses a distinct set of proteins. ERCs, though morphologically appearing mesenchymal, were found to express only some, but not all, proteins characteristic of MSCs. Additionally, ERCs were reported to be able to differentiate into, or become, cells from the three different germ layers (see the previous post on MSCs for more details): mesoderm (muscle, bone, fat, cartilage, and endothelial cells), ectoderm (neurons), and endoderm (liver, pancreas, and lung cells) (Meng et al., 2007; Patel et al., 2008). However, the mesenchymal stem cells from the intact endometrium cannot generate cells from all three germ layers. Overall, ERCs were determined to be functionally distinct from endometrium MSCs (Meng et al., 2007; Hida et al., 2008).

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Potential of Stem Cells to Cure HIV

March 1st, 2009

Recently, a patient with leukemia and human immunodeficiency virus (HIV) had apparent remission of both after stem cell transplants (Hütter et al., 2009). As discussed earlier, hematopoietic stem cells have been used in transplants to rescue patients with leukemia, but this method has not previously been as successful for treating HIV, the virus that causes acquired immunodeficiency syndrome (AIDS).

Once in the body, HIV primarily attacks the immune system, such as T cells, though some individuals have T cells that are naturally resistant to HIV infection. Over a decade ago, this resistance was found to be due to a mutation in a receptor that is normally on the cell surface of T cells, called chemokine receptor 5 (CCR5) (Liu et al., 1996). CCR5 is a chemokine receptor, meaning it normally binds and receives signals from chemokines, which are molecules cells can release and receive to cause an immune system response. CCR5 is thought to normally be involved in causing a response to infection, though its exact function is not fully understood. HIV normally interacts with CCR5 to gain entry into the target T cell, but some individuals have a mutation in the CCR5 gene, specifically a 32 base-pair deletion, that renders the resultant receptor completely nonfunctional and consequently prevents HIV from being taken into these cells (Liu et al., 1996).

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The T cell membrane (shown as the purple, semicircle double line) allows entry of HIV (in pink) into the cell through multiple cell receptors anchored on the membrane, including CCR5.

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Hematopoietic Stem Cells: A Long History in Brief

February 21st, 2009

Promising cures for blood-related diseases, such as leukemia and lymphoma, hematopoietic stem cells (HSCs) have been heavily researched for decades. However, like many significant findings in science, their discovery was not made in search for such a cure, but stumbled upon while dealing with another serious medical issue of the time: radiation. While trying to treat people exposed to lethal doses of radiation during World War II, transplants from the spleen and bone marrow were found to rescue these victims (Ford et al., 1956). It was not until later that scientists determined that the HSCs present in these tissues were what was restoring the damaged tissues, observed by performing transplants using lethally irradiated mouse and rat models (Becker et al., 1963). HSCs in humans were further characterized and cultured in the 1980s (Morstyn et al., 1980; Sutherland et al., 1989; Sutherland et al., 1990). The formation of the National Marrow Donor Program during this time also greatly improved the availability of these cells for research. Not only have HSCs been successfully used clinically in humans since the 1950s, but to this day they are still one of the few adult stem cells to be tested for clinical uses.

It is now not only better understood how HSCs from a donor animal can save a lethally irradiated recipient animal, but how HSCs can be used in many other medical applications as well. HSCs are able to give rise to all cells in the hematopoietic system, which includes myeloid elements (i.e. red blood cells, white blood cells, platelets) and the lymphatic system (i.e. T-Cells) (Regenerative Medicine, 2006). Because radiation generally targets rapidly dividing cells, including bone marrow cells and cells in the lymphatic system, HSCs have the ability to replenish the supply of cells most damaged by radiation. While HSCs can be collected from adult bone marrow, some fetal tissues (liver, spleen, thymus), umbilical chords, and peripheral blood, in recent years there has been a great shift towards obtaining HSCs mainly from peripheral blood, using a much simpler and less controversial procedure, though achieving a large enough number of HSCs for transplants is still an obstacle to overcome (Stem Cells, 2001). HSCs are now being used to treat cancers of the hematopoietic system (leukemia and lymphomas), replenish cells lost to high-doses of chemotherapy, and fight against autoimmune diseases, in addition to other medical applications (Regenerative Medicine, 2006).

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Hematopoietic stem cells give rise to two major progenitor cell lineages, myeloid and lymphoid progenitors (Regenerative Medicine, 2006).

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