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Lessons
on regrowth, on a small scale
The dream of regenerative medicine is that it will one day be possible to replace flawed tissues — to create a new spinal cord, repair a defective heart, or regrow a limb. But as scientists make steady progress toward that tantalizing goal, some are studying a range of simple organisms, from tadpoles to salamanders to flatworms, that can already rebuild complete limbs or tails.
In his laboratory at Tufts University, biology professor Michael Levin is investigating an often-overlooked mechanism that may play a key role in triggering this regenerative capacity in such critters: electrical signals.
When people think of electricity in the body, they usually think of brain and nerve cells, or muscles. But Levin and other scientists study the bioelectrical signals that exist in all cells, and the role those play in allowing organisms to generate precise, functional replacements for body parts.
“You get a normal tail — not a tiny tail, not a huge tail, not a tail with a tumor,’’ Levin said. “The tail is of the right size and shape, and that’s not because we know how to tell a tail what shape to be. It’s because we’ve induced the host to build it.’’
Levin has altered the electrical signaling in cells and observed dramatic effects: A tadpole can regenerate a completely normal tail after it has lost that ability.
In a study published in the Journal of Neuroscience this fall, Levin and colleagues triggered that regeneration using drugs that affected the bioelectrical signaling in tadpoles. The drug increased the transport of sodium into cells, triggering the tadpoles to regrow perfectly formed tails, which include a complex mixture of tissues including spinal cord, muscle, and skin.
Levin’s hope is that electrical signals might be a master switch that allows the organism to boot up its regenerative program, rather than requiring scientists to build a new organ or appendage cell by cell.
“There are lots of subroutines that build things, and what you want to do is activate the topmost one — the one that says, ‘Build a limb,’ ’’ Levin said. “These electrical properties sit fairly upstream, regulating a lot of coordinated stuff down below.’’
He is extending the work to investigate how electrical signals might be important in eye development, facial birth defects, and limb regeneration. In work funded by the Defense Advanced Research Projects Agency, he is collaborating with Tufts bioengineer David Kaplan to create a regenerative sleeve that could sit at the site of an amputated limb and control bioelectrical signals that help spur the growth of a new limb.
The work is being done in mice, but ultimately, researchers aim to create a sleeve that could help people who lose their limbs. Now, they are trying to develop chemical cocktails that could regulate bioelectrical signals, mimicking those found in regenerative creatures.
Dr. Min Zhao, a dermatology professor at the University of California Davis, has also been studying electrical signaling — not for its ability to regenerate new limbs, but for the role it may play in orchestrating the repair of wounds.
In a 2006 paper published in Nature, he found that bioelectrical signaling was an overriding cue that guides cells involved in healing.
The research, he said, could be clinically relevant if drugs that tweak bioelectrical signals at a wound site are able to expedite or increase healing.
Scientists are building better tools to understand this aspect of cells. Charles Lieber, a professor of chemistry and chemical biology at Harvard University, earlier this year developed a nanoscale transistor so small that it could fit into a cell.
“This will enable totally new types of measurements that will help a broad class of biomedical researchers to do things they couldn’t do before,’’ Lieber said.
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