Organs, Heal Thyselves!
by David Pescovitz
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Irina Conboy is also affiliated with the California Institute for Quantitative Biomedical Research (QB3).
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As we reach middle age, our body starts to fail us. Brittle bones are more susceptible to breaking. Torn muscle is much slower to mend. Organs like the liver can become diseased and stop regenerating themselves. Can our body's natural self-repair mechanisms be reset though? UC Berkeley bioengineer Irina Conboy thinks so. She and her colleagues are developing an injectable nanomaterial that could potentially spur aged organs to heal themselves again.
"The regenerative properties of organs are tied to the behavior of stem cells," she says. "So I focus on what happens to those cells with aging. Why don't they work anymore and can we fix them?"
Stem cells are undifferentiated cells that can self-renew and differentiate into specialized cells of the organ or tissue in which they're found, a liver or muscle for example. Because adult stem cells can renew themselves, they're responsible for maintaining and repairing the tissue or organ.
A phase contrast image of a human embryonic stem cell colony.
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The problem is that as the body ages, the molecules that regulate stem cells eventually change and inhibit their regenerative properties. Simply adding a new supply of stem cells to a damaged muscle, for instance, won't work because the foreign environment will interfere with the cells' behavior.
"They'll quickly stop repairing the muscle," Conboy says. "But if you can supplement them with regulatory factors and also protect them somewhat from the aged environment, they'll behave better."
Mouse heart injected with hydrogel specially-prepared to fluoresce red. Scale bar indicates 10 microns. (courtesy Kevin Healy)
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Conboy and colleague Kevin Healy, a professor with joint appointments in Berkeley 's departments of Materials Science and Engineering and Bioengineering, and chemical engineering professor David Schaffer are working on a novel biomaterial with just those characteristics. For several years, Healy and his graduate students have been developing a hydrogel, a polymer-based matrix for directing stem cell growth. At room temperature, the material is flexible. But once it hits body temperature, it stiffens into a scaffold where the cells can grow. The scaffold eventually degrades and is absorbed by the body.
Multimedia
 Movie: When the injectable hydrogel reaches a temperature above 34 degrees Celsius, it undergoes a phase transformation and stiffens. (Quicktime movie)
Movie courtesy Kevin Healy
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The beauty of the gel is that various growth factors, peptide sequences, and other biomaterials can be added to the mix to encourage the growth of the stem cells. The stem cell-seeded hydrogel can then be injected directly into the body with a syringe or catheter.
"The hydrogel acts like a protective vehicle for the stem cells," Conboy says. "So for a couple of days, the stem cells are contained in an optimal environment for growth and hopefully they'll regenerate even diseased or old muscle."
Right now, the researchers are conducting in vitro experiments to study how adult muscle stem cells from a mouse behave in gels. Soon though, they hope to transplant the scaffold into young and old animals with muscle injuries in hopes that the tissue will regenerate itself.
According to Conboy, the research could potentially lead to treatments for degenerative diseases like muscular dystrophy and therapies for other tissue such as the brain or circulatory system. The long-term goal is to remove malfunctioning stem cells from an aged or diseased organ, seed them into the hydrogel, and inject the biomaterial back into the body to improve the repair process.
"Right now, our health plateaus before 40 and then begins to drop," Conboy says. "But I'm optimistic that you could actually feel pretty good until 90 or so."
Irina Conboy bio (pdf)
"The Heart of Tissue Engineering" by David Pescovitz (Lab Notes, December 2000)
Healy Biomaterials Group
California Institute for Quantitative Biomedical Research (QB3)
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