Stem cells have remarkable qualities

Imagine being able to print out a new knee—not the plastic-and-metal kind, but one made of real bone, ligament and cartilage cells. Science fiction? Yes, for now. “But it’s probably not as far off as it sounds,” says Christopher Centeno, M.D., a Broomfield-based specialist in orthopedic regenerative medicine. “It’s on the 20-to-25-year horizon.”

In fact, as some stem-cell researchers look into the future, there’s not much they envision the tiny building blocks of life won’t be able to do.

Stem cells have remarkable qualities. They are able to divide themselves for long periods of time, sometimes even after inactivity. They are unspecialized, with the potential to develop into many different types of cells, and in some tissues, such as those in the gut, they replicate throughout one’s life to repair and replenish worn-out tissues. (Some cell types, such as nerve, blood and muscle cells, do not normally replicate.)

Three Types of Stem Cells

Stem cells have different levels of specialization. “Totipotent” stem cells arise in the first few days after an egg is fertilized, and are able, under the right conditions, to develop into a viable embryo. Within days, these cells become “pluripotent,” able to differentiate and generate all the various cells in the body. “Multipotent” (sometimes called “adult” or “somatic”) stem cells are tissue-specific and can develop the cell types within a particular tissue or organ. Adult brain stem cells, for instance, can generate neurons and glial cells. Blood stem cells, transferred through bone-marrow transplant or collected in umbilical cord blood, are currently the most commonly used stem cells in therapy.

Until recently, researchers worked with both embryonic and nonembryonic adult stem cells. But 2006 brought a significant breakthrough: Scientists discovered ways to genetically “reprogram” specialized adult cells, such as those from the skin, to behave like pluripotent stem cells. Most current research focuses on these cells, called induced pluripotent stem cells (iPS cells). Skin biopsies can be taken from the patient being treated, reprogrammed into iPS cells, and then differentiated into adult stem cells corresponding to the tissue in need of regeneration. In addition to skirting ethical controversies, using iPS cells may eliminate the risk of rejection and the need for immunosuppressants.

Hair-Raising Results

Dennis Roop, Ph.D., directs the Gates Center for Regenerative Medicine at the University of Colorado’s Anschutz Medical Campus. Roop is preparing to use iPS cells in clinical trials for his research on inherited skin-fragility syndromes, or blistering skin diseases, which can be fatal. The use of iPS cells can induce skin cells to behave like youthful skin stem cells. “You kind of coach them,” Roop explains, by exposing them to factors such as human growth hormone and other chemicals. These factors, scientists have learned, direct the iPS cells to become a specific type of cell, like skin or bone or muscle. This could be particularly useful in treating skin diseases and chronic wounds.

Stem cells are proving useful in pharmaceutical testing as well. Gates Center researchers and the University of Colorado Cancer Center are among the first in the U.S. to test drugs that target and destroy cancer stem cells, which are the source of cancer. The therapy has proven effective in treating tumors and blood cancers in clinical trials. Another upcoming Gates Center study with significant potential in treating cancer focuses on removing blood stem cells from a patient before chemotherapy or radiation, growing and expanding those cells, and returning them to the patient’s body to restore blood stem cells that were damaged during the cancer treatment.

Though he can’t bioprint cells yet, Dr. Christopher Centeno does use stem-cell therapies to improve arthritis and ligament or tendon tears. Above, he injects stem cells into a patient’s knee.
Though he can’t bioprint cells yet, Dr. Christopher Centeno does use stem-cell therapies to improve arthritis and ligament or tendon tears. Above, he injects stem cells into a patient’s knee.

Scientists at the center are working to regenerate damaged lung tissue, as well as replenish the dopamine-secreting neurons that are destroyed in Parkinson’s disease. They are even fortifying muscle cells against aging, which may prove significant not only for the elderly but also for patients with muscular dystrophy. Research on how bone-marrow stem cells form fat cells—which make other cells less responsive to insulin—may have implications for treating type 2 diabetes.

The list of applications goes on. Scientists are now able to genetically correct defects in embryonic DNA. In the European Union, clinical trials have been approved to use corneal stem cells to repair eye tissue damaged by chemical spills or infections. Stem cells may offer treatments for patients with macular degeneration, stroke, burns and rheumatoid arthritis. On the lighter side, hairless mice are growing hair.

Orthopedic Applications

While we’re still far from “bioprinting” cells, Centeno has been using stem cells in his Regenexx orthopedic procedures for 10 years for arthritis and tears in tendons and ligaments. “If you have knee arthritis, it’s not going to grow you a new knee,” says Centeno, but on average he sees about 50-percent improvement, he says.

Roop and Centeno agree that while there is no scientific evidence that such a procedure will build new tissue, it does reduce inflammation. The injected stem cells may also release growth factors that stimulate the patient’s own stem cells to head into the injured site and do repairs.

Centeno says he sees a more robust response, with MRI images to prove it, in using the procedure to heal rotator cuff and ACL tears. “About two-thirds of those who normally get surgery, we can treat through precise injection and get good evidence of healing,” he says.

The FDA currently limits stem-cell therapies to same-day procedures. In Centeno’s Regenexx procedures, marrow is drawn from the patient’s pelvis in the morning and then processed to isolate and concentrate the stem cells, which are injected later in the day into the area where they’re needed. A small number of Centeno’s patients fly to Grand Cayman Island, whose laws allow stem cells to be cultured for a couple of weeks so that they multiply as much as 1,000-fold before reinjection.

Elixirs for Everything

Roop says that researchers have been working with congressional representatives to encourage the FDA to reform the way stem-cell–based therapies are approved. Treatments using stem cells are further off in the U.S. than they are in some countries, like Japan, because the FDA requires proof not only of safety (the requirement in Japan) but also of efficacy.

While therapies are currently limited, some companies, like Boulder-based Centagen (not connected to Centeno), are marketing nutraceuticals—specially treated foods, vitamins, minerals or herbs—to “promote healthy stem cells.” The plant-based products do not contain stem cells. Centeno’s facility has run lab-based research exposing supplements in culture to mesenchymal stem cells (the orthopedic-repair kind), with positive results. Glucosamine, chondroitin and curcumin all make the list. “These types of supplements help stem cells go in the direction we want them to go,” Centeno says.

In 20 years, Centeno predicts, probably 80 percent of orthopedics will be needle-based procedures. Looking ahead 30 to 40 years? “Cutting out whole parts of people and inserting metal replacements, disarticulating a hip to try to fix a labrum, and taking out an ACL to try to put in a tendon that will never really function the same way that the original ACL did—all that stuff will seem pretty nutty.” And thanks to tools like genetic editing, he says, arthritis may simply become an ailment of the past.

The possibilities seem endless. “Once you have the ability to make iPS cells you can think about almost any application,” says Roop. “There’s certainly data in animal models that suggests you might be able to regenerate entire organs, such as kidneys, or a liver, or a lung, or even the heart.”

And maybe, not so far off, we might have an elixir for youth.

Shannon Burgert, Ph.D., writes regularly about health and science for Boulder Magazine. She teaches fifth grade at Fireside Elementary School in Louisville and is an Ironman athlete.

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