Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Enzyme helps stem cells improve recovery from limb injuries

15.05.2014

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."

... more about:
»IDO »MCG »death »immune »inflammation »injuries »limb »mitochondria »therapy

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.

"They start to leak things that should not be outside the mitochondria," he said. Without adequate energy and with leaky powerhouses, cells quickly succumb. Inflammation, which is part of the normal healing process, escalates to help clean up the mess, but instead further exacerbates the problem.

While their findings were in limb injuries, the researchers say they should translate to the myriad of scenarios resulting in reperfusion injury. In fact, in just a short two hours in the operating room, Yu has seen free flaps, where tissue is moved from one area of the body to another to cover a burn or rebuild a breast, start dying from ischemia reperfusion injury.

"It cuts across many, many individual disease conditions," Yu said. Transplant centers already are experimenting with pulsing donor organs to avoid reperfusion trauma.

Next steps include seeing if more is better, by giving more stem cells – the researchers only gave one dose in the studies – as well as IDO-enhancing drugs, Baban said. This will include incubating stem cells with IDO, Baban said.

The researchers note that stem cell therapy isn't yet used to help patients' injured limbs recover, but is being studied clinically to aid stroke and heart attack recovery at MCG and other centers. Right now, the most physicians can do is restore blood flow and give broad-spectrum antibiotics.

"Sometimes it works, sometimes it doesn't," Yu said. "That is why this kind of pharmacologic intervention could be very, very important.

Endogenous stems cells enable the body to replace cells that are lost to wear and tear and aging. IDO is one of numerous immune modulators in the body. It remains unclear whether some individuals have higher IDO levels.

Dr. Mohamad Masoumy, a fourth-year general surgery resident at MCG and GR Health System, is first author on the PLOS ONE study.

###

Toni Baker
Communications Director
Medical College of Georgia
Georgia Regents University
706-721-4421 Office
706-825-6473 Cell
tbaker@gru.edu

Toni Baker | Eurek Alert!
Further information:
http://www.gru.edu

Further reports about: IDO MCG death immune inflammation injuries limb mitochondria therapy

More articles from Life Sciences:

nachricht Researchers discover new mechanism in adrenal gland tumors
28.08.2015 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Cells cling and spiral 'like vines' in first 3-D tissue scaffold for plants
27.08.2015 | University of Cambridge

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: OU astrophysicist and collaborators find supermassive black holes in quasar nearest Earth

A University of Oklahoma astrophysicist and his Chinese collaborator have found two supermassive black holes in Markarian 231, the nearest quasar to Earth, using observations from NASA's Hubble Space Telescope.

The discovery of two supermassive black holes--one larger one and a second, smaller one--are evidence of a binary black hole and suggests that supermassive...

Im Focus: What would a tsunami in the Mediterranean look like?

A team of European researchers have developed a model to simulate the impact of tsunamis generated by earthquakes and applied it to the Eastern Mediterranean. The results show how tsunami waves could hit and inundate coastal areas in southern Italy and Greece. The study is published today (27 August) in Ocean Science, an open access journal of the European Geosciences Union (EGU).

Though not as frequent as in the Pacific and Indian oceans, tsunamis also occur in the Mediterranean, mainly due to earthquakes generated when the African...

Im Focus: Self-healing landscape: landslides after earthquake

In mountainous regions earthquakes often cause strong landslides, which can be exacerbated by heavy rain. However, after an initial increase, the frequency of these mass wasting events, often enormous and dangerous, declines, in fact independently of meteorological events and aftershocks.

These new findings are presented by a German-Franco-Japanese team of geoscientists in the current issue of the journal Geology, under the lead of the GFZ...

Im Focus: FIC Proteins Send Bacteria Into Hibernation

Bacteria do not cease to amaze us with their survival strategies. A research team from the University of Basel's Biozentrum has now discovered how bacteria enter a sleep mode using a so-called FIC toxin. In the current issue of “Cell Reports”, the scientists describe the mechanism of action and also explain why their discovery provides new insights into the evolution of pathogens.

For many poisons there are antidotes which neutralize their toxic effect. Toxin-antitoxin systems in bacteria work in a similar manner: As long as a cell...

Im Focus: Fraunhofer IPA develops prototype of intelligent care cart

It comes when called, bringing care utensils with it and recording how they are used: Fraunhofer IPA is developing an intelligent care cart that provides care staff with physical and informational support in their day-to-day work. The scientists at Fraunhofer IPA have now completed a first prototype. In doing so, they are continuing in their efforts to improve working conditions in the care sector and are developing solutions designed to address the challenges of demographic change.

Technical assistance systems can improve the difficult working conditions in residential nursing homes and hospitals by helping the staff in their work and...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Networking conference in Heidelberg for outstanding mathematicians and computer scientists

20.08.2015 | Event News

Scientists meet in Münster for the world’s largest Chitin und Chitosan Conference

20.08.2015 | Event News

Large agribusiness management strategies

19.08.2015 | Event News

 
Latest News

OU astrophysicist and collaborators find supermassive black holes in quasar nearest Earth

28.08.2015 | Physics and Astronomy

Two satellites see newborn Tropical Storm Jimena consolidating

28.08.2015 | Earth Sciences

NASA's GPM satellite analyzes Tropical Storm Erika's rainfall

28.08.2015 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>