A Fetal Enzyme Helps Stem Cells Recover From Limb Injuries

April Flowers for redOrbit.com Your Universe Online

Nearly two million Americans a year suffer from ischemia reperfusion injuries. A wide variety of scenarios can be caused by these injuries that result in restricted blood flowfrom traumatic limb injuries, to heart attacks, to donor organs. Restoring the blood flow to an injured leg, for example, seems like it would be a good idea. A new study from Georgia Regents University, however, suggests that restoring the flow could cause additional damage that actually hinders recovery.

Rather than promoting recovery, restoring blood flow actually heightens inflammation and cell death 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 MCGs Section of Plastic and Reconstructive Surgery. All kinds of bad things start happening.

Yu collaborated with Dr. Babak Baban, immunologist at the Medical College of Georgia and College of Dental Medicine at Georgia Regents University. Their study, published in PLOS ONE, reveals that 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 mothers immune system.

Baban notes that previous studies have found a correlation between stem cells and recovery. The stem cells both enable new blood vessel growth and by turning down the now-severe inflammation. The new findings reveal that ndoleomine 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. IDO is expressed by stem cells and numerous other cell types.

Stem cell efficiency was boosted by approximately one-third when tested on animal models comparing the therapy in normal mice versus mice missing IDO.Decreased expression of inflammatory markers, swelling and cell death were all observed. These are all associated with shorter, improved recoveries.

We dont want to turn off the immune system, we want to turn it back to normal, Baban said.

Even a brief period of inadequate blood flow, and the resulting lack of nutrients, can start problems that result in the rapid accumulation of destructive acidic metabolites, free radicals, and damage to cell structures. Mitochondria, which are the cells power plants, should be producing the energy source ATP. Instead, they quickly become fat, leaky and dysfunctional in this situation.

The mitochondria are sick; they are very, very sick, Yu said. Enormous additional stress is added to these sick powerhouses when blood flow is restored.

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A Fetal Enzyme Helps Stem Cells Recover From Limb Injuries

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