Page 1 of 1: STEM CELL THERAPY -- RECENT ADVANCES

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Transplantation of progenitor cells derived from bone marrow after myocardial infarction may lead to improvement in cardiac ejection fraction, according to the results of a study published September 21, 2006 in The New England Journal of Medicine.

German researchers conducted a randomized, controlled, crossover study of 75 patients. All patients had had a myocardial infarction at least 3 months previously and had stable ischemic heart disease. The patients were assigned to 1 of 3 groups. One group served as the control group (n = 23). Patients assigned to the other 2 groups received infusions of progenitor cells into the patent coronary artery that supplied the most dyskinetic area of the left ventricle. The cells infused in one of the treatment groups (n = 28) were derived from bone marrow (BMC), and the cells infused in the other treatment group (n = 24) were derived from circulating blood (CBC).

Three months after the infusions were performed, all patients were crossed over to receive either initial or different infusions of progenitor cells. Those in the control group were randomly assigned to receive either BMC or CBC, those who initially received BMC received CBC, and those who initially received CBC received BMC.

Significantly greater absolute change in left ventricular ejection fraction was found in patients who received BMC (+2.9 percentage points) compared with those who received either CBC (–0.4 percentage point; P = .003) or no infusion (–1.2 percentage points; P < .001). Regional cardiac contractility in areas targeted by intracoronary infusion of BMC was significantly enhanced and was related to increases in global cardiac function. This same finding was noted in the patients who were crossed over to BMC after either no infusion or CPC infusion.

The researchers conclude that intracoronary infusion of BMC appears to be safe and effective in improving the left ventricular ejection fraction of patients with healed myocardial infarction.

In other news, it was reported that liver function may improve after the localized injection of autologous CD34+ cells into patients with hepatic insufficiency. The results of this study were published in the July 2006 issue of Stem Cells.

Dr Nagy A. Habib from Imperial College London in the United Kingdom and colleagues conducted a phase I study of 5 patients with hepatic insufficiency. According to background information provided in the article, the researchers hypothesized that CD34+ cell populations could contain a subset of cells that have the capacity to regenerate damaged tissue. Before conducting the clinical trial, the researchers analyzed CD34+ cells that had been applied to tissue culture and examined using reverse transcription-polymerase chain technology. They found evidence that the CD34+ population contained cells that may potentially form hepatocyte-like cells.

After gathering this supportive evidence, the researchers administered granulocyte colony-stimulating factor to the patients to promote mobilization of their stem cells. Cells were then collected by leukapheresis. Afterward, CD34+ cells—in quantities of between 1 × 106 and 2 × 108—were injected into the portal veins of 3 patients and into the hepatic arteries of 2 patients.

Adverse effects or complications related to the procedure were not observed. Four of 5 patients showed improvements in serum albumin results, and 3 of 5 demonstrated improved serum bilirubin results.

The researchers conclude that further clinical trials of this procedure in patients with hepatic insufficiency are warranted.

The following Clinical Topic Tour provides an overview of stem cell therapy and was adapted from materials published by the National Institutes of Health.

Definitions

Stem cells are unspecialized living cells that have the capacity to renew themselves for long periods of time through cell division. Under certain physiologic or experimental conditions, they can be induced to become cells with special functions such as the beating cells of the heart muscle or the insulin-producing cells of the pancreas.

Embryonic stem cells are derived from embryos. Specifically, embryonic stem cells are derived from embryos that develop from eggs that have been fertilized in vitro and then donated for research purposes with the informed consent of the donors. The embryos from which human embryonic stem cells are derived are typically 4 or 5 days old and consist of a hollow microscopic collection of cells called the blastocyst.

An adult stem cell is an undifferentiated cell found among differentiated cells in a 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 researchers now use the term somatic stem cell instead of adult stem cell. Unlike embryonic stem cells, which are defined by their origin, the origin of adult stem cells in mature tissues is unknown. A single adult stem cell could have the ability generate a line of genetically identical cells, or clones.

Somatic cell nuclear transfer is the scientific term for cloning and is a technique that combines an enucleated egg and the nucleus of a somatic cell to make an embryo.

Adult Stem Cells

Adult stem cells have been identified in many organs and tissues. Each tissue only contains a small number of stem cells. Stem cells are believed to reside in a specific area of each tissue where they may remain quiescent for many years until they are activated by disease or tissue injury. The adult tissues reported to contain stem cells include the brain, bone marrow, peripheral blood, blood vessels, skeletal muscle, skin, and liver.

Adult stem cells typically generate the cell types of the tissue in which they reside. A blood-forming adult stem cell in the bone marrow, for example, normally gives rise to cells such as red blood cells, B lymphocytes, T lymphocytes, natural killer cells, neutrophils, basophils, eosinophils, monocytes, macrophages, and platelets. Until recently, researchers believed that a blood-forming cell in the bone marrow—called a hematopoietic stem cell—could not give rise to the cells of different tissue, such as nerve cells in the brain. However, a number of experiments over the last several years have raised the possibility that stem cells from one tissue may be able to give rise to cell types of a completely different tissue, a phenomenon known as plasticity. Examples of such plasticity include blood cells becoming neurons, liver cells that can be made to produce insulin, and hematopoietic stem cells that can develop into myocardium.

In the 1960s, researchers discovered that bone marrow also contains at least one other type of stem cells, called bone marrow stromal cells. These cells, also known as mesenchymal stem cells, are a mixed cell population that generates bone cells (osteocytes), cartilage cells (chondrocytes), fat cells (adipocytes), and other kinds of connective tissue cells such as those in tendons.

Other types of adult stem cells include the following:
neural stem cells in the brain (give rise to 3 major cell types: neurons and 2 categories of non-neuronal cells known as astrocytes and oligodendrocytes);
epithelial stem cells in the lining of the digestive tract (give rise to absorptive cells, goblet cells, Paneth cells, and enteroendocrine cells); and
skin stem cells in the basal layer of the epidermis and at the base of hair follicles (give rise to keratinocytes).
A potential advantage of using stem cells from an adult is that a patient's own cells could be expanded in culture and then reintroduced. The use of a patient's own adult stem cells would obviate the possibility of rejection by the immune system.

Embryonic Stem Cells

Human embryonic stem cells are thought to have much greater developmental potential than adult stem cells.

Unlike adult stem cells, embryonic stem cells can become all cell types of the body because they are pluripotent. Large numbers of embryonic stem cells can be relatively easily grown in culture, whereas adult stem cells are rare in mature tissues and methods for expanding their numbers in cell culture have not yet been fully explored. This is an important distinction because large numbers of cells are needed for stem cell replacement therapies.

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 yet been determined in clinical studies.

Potential Uses for Stem Cells

Studies of human embryonic stem cells may yield information about the complex events that occur during human development. A primary goal of research in this area is to identify the processes by which undifferentiated stem cells become differentiated. A better understanding of the genetic and molecular controls of these processes may yield information about how diseases such as cancer and birth defects arise and may suggest new strategies for therapy.

Human stem cells could also be used to test new drugs. For example, new medications could be tested for safety on differentiated cells generated from human pluripotent cell lines. Other kinds of cell lines are already used in this way. Cancer cell lines, for example, are used to screen potential chemotherapeutic drugs.

Perhaps the most important potential application of human stem cells is the generation of cells and tissues that could be used for cell-based therapies. For example, stem cells, directed to differentiate into specific cell types, offer the possibility of a renewable source of replacement cells and tissues to treat diseases including Parkinson's and Alzheimer's diseases, spinal cord injury, stroke, burns, heart disease, diabetes, osteoarthritis, and rheumatoid arthritis.

Hematopoietic stem cells are currently the only type of stem cell commonly used to treat human diseases. These cells have been used in bone marrow transplants for over 40 years. More advanced techniques of harvesting these cells are now possible, and transplants of these cells are used to treat leukemia, lymphoma, and several inherited blood disorders.

The clinical potential of adult stem cells also has been demonstrated in the treatment of other human diseases that include diabetes and advanced kidney cancer. However, these newer uses have involved studies with a very limited number of patients.

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