Science Fact: Stem cell research is in the news again and the news is all good. The latest: stem cell technology can create an entire functioning organ; and can rebuild tissue in…(blare of trumpets, please!)…a human being.
We have already discussed several aspects of stem cell work: their discovery and use for bone marrow transplants; stem cell creation from skin cells, hair and other tissue; and stem cell generation of platelets, those specialized cell fragments that are critical to the proper functioning of our blood. I hope you’re not getting stem cell overdose! But when research results this significant and different appear, they deserve broad mention. That way, we can cheer on the scientists, and more importantly, we can be aware in case we or our loved ones can benefit from the healing results of their work.
Stem Cell Creation of a Functioning Organ
The first of these two reports comes from the Centre for Regenerative Medicine at Edinburgh University, UK. A team led by Professor Clare Blackburn has, for the first time, used programmed stem cells to build a complete and functioning organ in a living animal.
Unless you’re fond of sweetbreads, the thymus gland may not enter your everyday conversation. In humans, the thymus is located in the center of the chest, between the heart and the breastbone (sternum). The thymus is a critical part of the immune system because it produces T-cells that adapt to attack invading bacteria, viruses and cancer cells. The thymus is missing or malfunctioning in one of 4,000 babies, which makes them extremely susceptible to infection. Moreover, anyone whose thymus is defective is vulnerable, a situation that is especially serious when rebuilding a patient’s immune system after a bone marrow transplant.
The research team used stem cell technology to create a complete working thymus in laboratory mice. This was not a quick-and-easy experiment, it’s rather sophisticated work.
The researchers had previously succeeding in rejuvenating the thymus gland in elderly mice. They did so by giving the mice the drug tamoxifen, which is also used to block the growth of certain types of breast cancer. It turns out that tamoxifen stimulates a “transcription factor” FOXN1 that guides thymus development in the embryo, and also serves to rejuvenate the immune system in the mice.
Building on this previous work, in the most recent research the Edinburgh group modified mouse DNA to produce increased amounts of FOXN1, using “homologous recombination” of the genetic material. They then extracted connective tissue cells called fibroblasts from mouse embryos. These fibroblasts with enhanced FOXN1 behaved like the kind of stem cell that becomes a thymus cell in an embryo. The cells were grafted onto the kidneys of genetically identical mice. Within a month, the cells had grown into a complete thymus organ with clearly defined parts (the cortex and the medulla), all cell types present, and providing T cells to the immune system.
Although this thymus work was carried out in laboratory mice, mice constitute an important laboratory model; they are traditionally used to study the immune system in order to develop treatments for immune-deficient humans. Thus the creation of a full functioning organ within a living animal, an organ similar to an essential part of the human system, counts as an important step in biomedical research.
Stem Cell Reconstruction of Human Muscle
If you fear that mice are the only beneficiaries of stem cell research, you’ll be relieved to know that stem cell technology has also shown great success in rebuilding muscles in an actual human patient. In this case, the stem cells naturally occur within the human body as “progenitor cells”. A progenitor cell is a stem cell that has already partially differentiated, so it can only form certain kinds of tissue. The particular type of cell that is needed to grow muscle is called a myoblast. Our bodies develop having an excess of myoblasts: those that do not transform into muscle revert to a previous state, that of satellite cell, and are stored in the muscle tissue.
All right, you might say, if satellite cells are hanging around with nothing to do, ready to form myoblasts and grow into muscle, why can’t we just regenerate any muscle that we lose to injury or disease?
Here’s the key problem: if we lose a small amount of muscle in an injury, it can regenerate with the help of physical therapy. However, if the loss exceeds approximately twenty percent of the muscle, the damage becomes permanent and the gap in the muscle fills in with scar tissue.
Why can’t more than twenty percent of the muscle regenerate? The answer seems to be that you need more than just satellite cells and physical therapy. You also need a structure, a framework, to attract the satellite cells and define where the muscle should grow.
Dr. Stephen Badylak and his colleagues have developed a powerful technique to promote the re-growth of damaged muscle as described in a review article. They take an “extracellular matrix” (ECM), essentially a network of collagen, obtained from a pig’s urinary bladder. The researchers remove all traces of cells from this collagen scaffold so that the human recipient’s immune system will not reject it. The ECM is then implanted at the site of the missing muscle. As the matrix slowly degrades, chemicals are released that attract satellite cells, which in turn form myoblasts which differentiate into muscle fibers.
Amazingly, the formation of muscle tissue is accompanied by the formation of blood vessels and nerve connections. Simultaneous physical therapy appears to be necessary to help the body understand that it needs to form functional muscle tissue. Most importantly, tissue death and scar tissue formation do not occur during the formation of new muscle. A VOANews article describes the repair of a skier’s left calf following a serious ski accident, using Dr. Badylak’s procedure.
Science Speculation: The two research reports described above help dramatize both the power and the complexity of stem cell therapies. In both cases, remarkable progress has been made even though the underlying biological processes are not completely understood.
In the Edinburgh work, the growth of a functioning thymus gland is a remarkable feat, requiring the integration of advanced stem cell and genetic transfer techniques. Although it arises from previous work on genetic transcription factors, it goes far beyond that work in its scope. The fact that this work has not yet been transferred to human use reflects the extreme complexity of creating complete organs, and does not detract from the fine work accomplished to date.
The Badylak work similarly involves the integration of multiple threads: the development of a cellular matrix that can be implanted without fear of rejection; physical therapy to cue the body’s response; and the body’s own repair mechanism, stimulated to go far beyond its usual capabilities. Pig-derived collagen scaffolds have to date been used for tissue repair in over 100,000 human patients, an outstanding example of success for the stem cell technology reported here.
We can offer unstinting praise to these researchers who are not content to just do science, but who actively address such serious needs as organ renewal and replacement, and the repair of major tissue injuries.
Do you know anyone who has personally benefited from stem cell medical technology?
Image Credit: “Bicep” from The Print Shop 2 Collection. Not for download or reuse.