Enzyme helps stem cells improve recovery from limb injuries

While it seems like restoring blood flow to an injured leg would be a good thing, it can actually cause additional damage that hinders recovery, researchers say.

Ischemia reperfusion injury affects nearly two million Americans annually with a wide variety of scenarios that temporarily impede blood flow -- from traumatic limb injuries, to heart attacks, to donor organs, said Dr. Babak Baban, immunologist at the Medical College of Georgia and College of Dental Medicine at Georgia Regents University.

Restoring blood flow actually heightens inflammation and cell death rather than recovery for many of these patients.

"Think about trying to hold onto a nuclear power plant after you unplug the electricity and cannot pump water to cool it down," said Dr. Jack Yu, Chief of MCG's Section of Plastic and Reconstructive Surgery. "All kinds of bad things start happening."

Baban and Yu are collaborators on a study published in the journal PLOS ONE that shows one way stem cell therapy appears to intervene is with the help of an enzyme also used by a fetus to escape rejection by the mother's immune system.

Earlier studies indicate stem cells may improve recovery both by enabling new blood vessel growth and by turning down the now-severe inflammation, Baban said. The new study shows that indoleomine 2,3 dioxygenase, or IDO, widely known to dampen the immune response and create tolerance, plays an important role in regulating inflammation in that scenario. Stems cells and numerous other cell types are known to express IDO.

In fact, IDO boosted stem cell efficacy by about a third in their studies in animal models comparing the therapy in normal mice versus mice missing IDO. The researchers documented decreased expression of inflammatory markers, swelling and cell death, which correlate with a shorter, improved recovery.

That could be just what the doctor ordered for these patients, said Baban, the study's corresponding author. "We don't want to turn off the immune system, we want to turn it back to normal," he said.

Problems start with even a short period of inadequate blood and nutrients resulting in the rapid accumulation of destructive acidic metabolites, free radicals, and damage to cell structures, Yu said. Cell power plants, called mitochondria, which should be producing the energy source ATP, are among the early casualties, quickly becoming fat, leaky, and dysfunctional.

"The mitochondria are sick; they are very, very sick," Yu said. When blood flow is restored, it can put huge additional stress on sick powerhouses.

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Enzyme helps stem cells improve recovery from limb injuries