Unit Three. The Continuity of Life
13. The New Biology
13.7. Stem Cell Therapy
You can see a mass of human embryonic stem cells in figure 13.16. Many are totipotent—able to form any body tissue, and even an entire adult animal. What is an embryonic stem cell, and why is it totipotent? To answer this question, we need to consider for a moment where an embryo comes from. At the dawn of a human life, a sperm fertilizes an egg to create a single cell destined to become a child. As development commences, that cell begins to divide, producing after four divisions a small mass of 16 embryonic stem cells. Each of these embryonic stem cells has all of the genes needed to produce a normal individual.
Figure 13.16. Human embryonic stem cells (x20).
This mass is a colony of undifferentiated human embryonic stem cells growing in tissue culture and surrounded by fibroblasts (elongated cells) that serve as a "feeder layer."
As development proceeds, some of these embryonic stem cells become committed to forming specific types of tissues, such as nerve tissues, and, after this step is taken, cannot ever produce any other kind of cell. In the case of nerve tissue, they are then called nerve stem cells. Others become specialized to produce blood cells, others to produce muscle tissue, and still others to form the other tissues of the body. Each major tissue is formed from its own kind of tissue-specific adult stem cell. Because an adult stem cell forms only that one kind of tissue, it is not totipotent.
Using Stem Cells to Repair Damaged Tissues
Embryonic stem cells offer the exciting possibility of restoring damaged tissues. To understand how, follow along in figure 13.18. A few days after fertilization, an embryonic stage called the blastocyst forms 1. Embryonic stem cells are harvested from its inner cell mass or from cells of the embryo at a later stage 2. These embryonic stem cells can be grown in tissue culture as seen in figure 13.16, and in principle be induced to form any type of tissue in the body 3. The resulting healthy tissue can then be injected into the patient where it will grow and replace damaged tissue 4. Alternatively, where possible, adult stem cells can be isolated and when injected back into the body, can form certain types of tissue cells.
Both adult and embryonic stem cell transfer experiments have been carried out successfully in mice. Adult blood stem cells have been used to cure leukemia. Heart muscle cells grown from mouse embryonic stem cells have successfully replaced the damaged heart tissue of a living mouse. In other experiments, damaged spinal neurons have been partially repaired. DOPA-producing neurons of mouse brains, whose loss is responsible for Parkinson’s disease, have been successfully replaced with embryonic stem cells, as have islet cells of the pancreas, whose loss leads to juvenile diabetes.
Because the course of development is broadly similar in all mammals, these experiments in mice suggest exciting possibilities for stem cell therapy in humans. The hope is that individuals with Parkinson’s disease, like Michael J. Fox (figure 13.17), might be partially or fully cured with stem cell therapy. As you might imagine, work proceeds intensively in this field of research.
Figure 13.17 Promoting a cure for Parkinson's.
Michael J. Fox, with whom you may be familiar as a star of the Back to the Future film series and the TV show Family Ties, is a victim of Parkinson's disease, and a prominent spokesman for those who suffer from it. Here you see him testifying before the U.S. Senate (along with fellow advocate Mary Tyler Moore) on the need for vigorous efforts to support research seeking a cure.
There are ethical objections to using embryonic stems cells but new experimental results hint at ways around this ethical maze. In 2007, researchers in two independent laboratories reported that they had engineered embryonic stemlike cells from normal adult human skin cells. The cells they created were pluripotent—they could differentiate into many different cell types. Whether pluripotency extends to totipotency is still being investigated. How were these cells transformed? The essential clue came six years earlier, when fusing adult cells with embryonic stem cells transformed the adult cells into pluripotent cells, as if factors had been transmitted to the adult cells that conferred pluripotency. Then, in a crucial advance in 2006, Japanese cell biologist Shinya Yamanaka introduced into adult human skin cells not the entire contents of an embryonic stem cell, but just the genes for four transcription factors. Once inside, these four factors induced a series of events that converted the adult cell to pluripotency. In effect, he had found a way to reprogram the adult cells to be embryonic stem cells. From proof-of-principle in a laboratory culture dish to actual medical application is still a leap, but the possibility is exciting.
Figure 13.18. Using embryonic stem cells to restore damaged tissue.
Embryonic stem cells can develop into any body tissue. Methods for growing the tissue and using it to repair damaged tissue in adults, such as the brain cells of multiple sclerosis patients, heart muscle, and spinal nerves, are being developed.
Key Learning Outcome 13.7. Human adult and embryonic stem cells offer the possibility of replacing damaged or lost human tissues.