Human Adult Stem Cells
Most of the cells of the human body are terminally differentiated. That is, the cells of our organs, such as those of the lung, liver, kidney, and brain, have reached their final specialized state. However, there are some cells that hold back and remain stem cells; they continue to deliver new specialized cells to the bodies of humans that they need to continue living. These cells share the two main characteristics of stem cells: they can renew themselves, and they can give rise to new specialized cells. They are known as Adult Stem Cells because, as noted, they are found in the bodies of adults—although they also can be found in infants, fetuses, placentas, and umbilical cord blood--. The primary role of these cells is to replace cells in the body that deteriorate because of injury or disease.
Although adult stem cells are rare, they have been found in bone marrow, blood vessels, peripheral blood, cornea, retina, brain, spinal cord, skeletal muscle, dental pulp, liver, skin, gastrointestinal tract, and pancreas. Scientists are attempting to grow these cells in culture and direct them to generate specific cell types that can be used to treat disease and injury in humans. For example, they hope to develop insulin-producing cells from adult stem cells found in the pancreas to treat those with type I diabetes and to produce cardiac muscle cells from adult stem cells dwelling in the heart to repair heart muscles that have been damaged by heart attacks. Because adult stem cells tend to lose their ability for self-renewal as the body ages, some investigators have used adult stem cells derived from the donated tissue of miscarried and aborted fetuses in studies. For instance, researchers at the University of California have transplanted human neural fetal stem cells into mice with spinal cord injuries, producing some improvements. Such investigations may pave the way for future testing in humans.
Debate about Adult Stem Cell Versatility
It had long been thought that adult stem cells are prone to become only a few of the specialized cell types of the body. Each type of adult stem cell, it was maintained, could only generate cell types derived from the layer of the developing embryo in which it originates. It was believed that the middle layer of the embryo, for instance, could only generate blood, muscle, cartilage, endothelial cells, and cardiac cells. Moreover, it was thought that a cell fated to make blood cells could not make pancreatic or liver cells, and a cell fated to make neurons could not make blood or muscle cells. Some investigators have recently challenged this view.
In the last decade, a number of published studies have suggested that adult stem cells from one tissue are capable of developing into cell types characteristic of other tissues. Scientists have reported finding that Neural stem cells became blood cells and muscle cells; Bone marrow stem cells generated cells akin to neurons and heart tissue; Bone marrow and hematopoietic stem cells gave rise to muscle cells. Indeed, investigators in one study found that a single cell from the bone marrow of an adult mouse had contributed not only to the bone and blood but also to the lung tissue, liver, intestine, and skin of experimental mice. Such studies supported the newly emerging view that a stem cell from one adult tissue can generate the differentiated cell types of certain other tissues when given the opportunity through experimental interventions. This phenomenon has been termed stem cell ‘‘plasticity.’’
The concept of the plasticity of human adult stem cells came to greater public attention in 2002 when Catherine Verfaillie of the University of Minnesota and her colleagues reported finding that rare adult bone marrow progenitor stem cells of mice could differentiate into a wider variety of specialized cells than had been previously been found, although not all of the specialized cells of the human body. When these adult bone marrow stem cells were transplanted into host animals, they entered into many different tissue types, including liver, lung, and intestine, where they differentiated into cell types appropriate to that tissue or organ. This report and others seemed to
signify that adult stem cells are pluripotent and can produce almost any cell of the body. In short, this work suggested that an adult stem cell may be able to become any other cell, given certain permissive or instructive conditions.
The new thesis of the plasticity of adult stem cells was startling, for it went against some thirty-five years of previous research and thought. Not surprisingly, it was greeted with both excitement and skepticism. The versatility of certain adult stem cells that this new research displayed made them attractive as therapeutic agents. Taking stem cells from healthy tissue in one part of an individual’s body to repair and regenerate diseased tissue in another part, it was speculated, would avoid the immunological rejection problem that can arise when transplanting cells, tissue, and organs from one individual to another. Other studies questioned these novel claims about the plasticity of adult stem cells, however. Some investigators could not reproduce the results of certain studies that had been said to demonstrate such plasticity in adult stem cells.
For instance, Derek van der Kooy and colleagues reported that they were unable to reproduce studies exhibiting a contribution of adult neural stem cells to blood cells. Several other investigators who found that earlier reports of adult stem cell plasticity could not be repeated called into question their experimental design. These findings, although not without critics of their own, put into question several previous studies that had been heralded as exhibiting the plasticity of adult stem cells. Some investigators who questioned the plasticity of adult stem cells explained this phenomenon in terms of cell fusion, hypothesizing that the inserted adult stem cells had simply merged with already existing differentiated cells in the recipients. Thus, these investigators proposed that fusion, rather than differentiation across cell types, explained the seeming plasticity of adult stem cells. They concluded that the potential of adult stem cells to generate cells of other types is limited.
The debate about the plasticity of adult stem cells has not yet been resolved. The question of whether adult stem cells can differentiate into cell types outside their own lineage is one of the most important issues that stem cell scientists face today. Just what occurs when adult stem cells transform into other sorts of cells, how efficient this process is, whether it is rare or common, and whether it has a role in the repair of tissue are still open questions. Many of the studies cited were carried out in mouse cells, which exhibit considerable plasticity. However, there are fewer cases in which human adult stem cells have exhibited such plasticity and have transdifferentiated into cells outside their lineage.