Adult Stem CellsOctober 2007
By Denis Rodgerson, PhD, Ron Rothenberg, MD, FACEP, and Wayne A. Marasco, MD, PhD
Life Extension Magazine
By Denis Rodgerson, PhD, Ron Rothenberg, MD, FACEP, and Wayne A. Marasco, MD, PhD
The potential to heal once incurable degenerative diseases such as cancer or heart disease by regenerating cells that have failed or are about to fail is now within our grasp, thanks to the emergence of an exciting new field of medicine: regenerative medicine using adult stem cells.
Indeed, tissues such as heart muscle that were long thought to be non-renewable have now been shown to be regenerated through this novel therapy. By using adult stem cells, scientists have avoided the controversy that has stymied advanced embryonic stem cell research in the past. Adult stem cell therapy offers an unprecedented step forward in the history of medicine and the applications of this new form of regenerative medicine are potentially unlimited.
Embryonic versus Adult Stem Cells
Considerable confusion surrounds the use of stem cells, not only with the general public, but indeed with scientists and physicians. This confusion has been compounded by the ethical, moral, and political issues that have arisen around the sources of stem cells. Broadly speaking, there are two classifications of stem cells: those that are derived from embryos (embryonic stem cells, ESCs) and those that come from other sources (adult stem cells [ASCs] or somatic stem cells). All stem cells, whatever their source, have three general properties: they are capable of dividing and renewing themselves for long periods; they are undifferentiated; and they have the ability to develop into specialized cell types.
Embryonic stem cells are derived from a clump of cells formed after fertilization, which is called the inner cell mass (ICM). The cells of the ICM rapidly differentiate to form all of the cell types in the human body, hence creating a fetus and then a human being. If the cells of the ICM are harvested and grown in appropriate culture conditions, however, they will replicate indefinitely and, when suitably stimulated, will differentiate into three germ layers: ectoderm, mesoderm, and endoderm—representing any cell lineage of the body. This potential to differentiate into any other cell type in the body is referred to as plasticity (or pluripotency).1 Given their high degree of plasticity, however, embryonic stem cells not only have the capability of becoming beneficial tissue, they also can differentiate into cancerous (malignant) cells. While it has recently been reported that these cells can be derived from sources other than embryos, there is broad consensus that much more research is required before human therapies based on embryonic stem cells can be safely pursued.2 Thus, while these cells have great importance in unraveling the processes by which cells proliferate and differentiate, there are currently no approved treatments or human trials using embryonic stem cells.
In contrast, adult stem cells are derived from non-embryonic origins, including bone marrow, peripheral blood and, paradoxically, cord blood, placental cells, and amniotic fluid (note that cord blood and placental cells must be collected and banked at the time of birth for future use, while amniotic fluid is drawn from the fluid surrounding a growing fetus). Adult stem cells are thought to be capable of facilitating all the body’s natural repair processes. Since the production of adult stem cells does not require the destruction of an embryo, these cells are not associated with any ethical or political controversy. Readily obtainable, these cells have been used for many years for therapeutic purposes.
Adult Stem Cell Therapies
It was initially believed that the ability of adult stem cells to regenerate tissue was limited to the type of tissue in which they resided. This is now known not to be the case. Numerous studies have confirmed that, although these cells do not have the universality of the embryonic type, they do have the capacity for self-renewal, are able to differentiate into other cell types and are capable of generating differentiated cell progenitors (similar to stem cells) of different (perhaps all) cell lineages. Their potential to differentiate into cell types found in other tissues means they can travel to a site of damage, penetrate the damaged tissue, and then regenerate this tissue by a process called transdifferentiation. It is these properties that have formed the basis for therapies in which adult stem cells have been used.
Bone Marrow Transplants: Adjuvant Cancer Care
One of the areas in which adult stem cells have become widely used is in the treatment of blood cancers including leukemia, lymphoma, and multiple myeloma. Since the 1990s, bone marrow transplants using blood-derived stem cells, which are capable of generating all cell types of the blood and immune system, have been used to regenerate bone marrow damaged by the effects of chemotherapy and/or radiation. Without healthy bone marrow, patients with these cancers cannot make the blood cells needed to carry oxygen, fight infection, and heal wounds. Healthy, transplanted bone marrow therefore restores these functions.
Stem Cell Donors
Often, because of the lack of an identical donor, adult stem cells obtained from a genetically well-matched healthy donor are infused into the affected recipient (known as “allogeneic” infusion, as opposed to using a recipient’s own stem cells) to create a healthy immune system free of cancer. These donor stem cells are obtained by a technique called apheresis, in which a machine selectively separates stem cells from donor blood and returns the rest of the blood to the donor. During this process, the donor most often receives a medicine (or “mobilizing agent”) called granulocyte colony-stimulating factor, which stimulates the bone marrow to release stem cells into the bloodstream where they can be easily collected after several days of treatment. Although this method has proved successful in providing sustained remission or cures of underlying diseases, donor stem cells do pose problems in that they can either be rejected by the recipient’s immune system or they may attack the recipient’s cells in a serious condition called graft-versus-host disease. In order to reduce the magnitude of rejection and graft-versus-host disease, tissue from both the donor and recipient must be matched to be as compatible as possible. Often, recipients must take immunosuppressive drugs for the rest of their lives to prevent rejection, which is associated with morbidities such as increased risk of serious infections.3,4
An alternative to using closely matched donor stem cells (“allogeneic” infusion) is to use the recipient’s own stem cells, known as “autologous” infusion. The use of these “autologous” cells avoids all of the problems associated with donor stem cells and also confers significant clinical and economic benefits. Intuitively, collecting and banking blood-derived stem cells many years before the onset of disease, known as pre-disease harvesting, should minimize the presence of tumor cells or tumor stem cells. Furthermore, banking an individual’s own stem cells may one day be life-saving in the event—particularly in those with strong family or occupational related risk factors for cancer—that a diseased organ needs to be replaced with one grown from their own cells.
Restoring Heart Function
Heart disease shows some of the greatest potential for the application of stem cells. Ischemic heart disease accounts for approximately half of all cardiovascular deaths in the United States, with over one million people suffering a heart attack each year. A heart attack leads to the death of the heart tissue and causes the muscle cells of the heart to be depleted. It also progressively remodels the structure of the heart, further reducing its ability to pump blood. For a long time, it was believed that the heart was a “post-mitotic” (non-renewable) organ composed of muscle cells that had completed the differentiation process, and therefore had limited capability of regeneration following an injury such as a heart attack. This belief is now being effectively challenged by mounting evidence to show that not only do endogenous self-repairing mechanisms exist, but that these and other regenerative processes, such as the development of new blood vessels, can be activated, or facilitated, by adult stem cells. These findings, and other observations, have led to a number of clinical trials that have tested the ability of stem cells to restore heart function in patients with acute heart disease. Early studies focused on establishing the safety and feasibility of using a patient’s own stem cells to improve heart function following a heart attack.5-7 Although research is ongoing, many controlled studies have also compared similar groups of patients on standard medical therapy after a heart attack with those on therapy plus an intracoronary infusion of their own stem cells. The results have been encouraging, revealing a positive effect of stem cell therapy on improving cardiac function outcomes, such as blood flow within the heart, wall motion, left ventricular function, and reducing the size of damaged heart tissue.8-17