Factor From Umbilical Cord Blood Could Treat Harmful Inflammation


Umbilical cord blood turns out to have a factor that can potentially fight inflammation, according to scientists at the University of Utah School of Medicine. This study was published online Sept. 6, 2016, in The Journal of Clinical Investigation.

“We found something we weren’t expecting, and it has taken us to new strategies for therapy that didn’t exist before,” says Guy Zimmerman, M.D., a professor of internal medicine at the University of Utah School of Medicine, who was also the senior author of this work. Dr. Zimmerman collaborated with associate professor of pediatrics, Christian Con Yost, M.D., and their colleagues for this work.

Inflammation is well-known to anyone who has whacked their leg, been stung by a bee or a wasp, or anyone who over-stressed their muscles. The redness, heat pain, and swelling are signs that the body is cleaning up damaged cells and their debris, fighting invading microorganisms, and beginning the healing process. However, under certain circumstances, inflammation can go overboard and turn against us and seriously and chronically damage healthy tissues. Out-of-control inflammation is probably the culprit behind several different conditions ranging from rheumatoid arthritis to sepsis. In fact, the inflammatory overreaction to infections is one of the most common causes of hospital deaths.

Dr. Yost and his coworkers successfully isolated a cord blood factor, called “neonatal NET inhibitory factor” or nNIF. This name comes from the ability of this factor to inhibit “NETs” or neutrophil extracellular traps. NETs or neutrophil extracellular traps are composed of processed chromatin bound to granular and selected cytoplasmic proteins that are released by white blood cells called neutrophils. NETs seem to be a kind of last resort that neutrophils turn to in order to control microbial infections. Even though NETs usually help our bodies ward off infectious bacteria and viruses, they can also damage blood vessels and organs during sepsis.

nets

As physicians who have treated critically ill patients suffering from out-of-control inflammation, Drs. Zimmerman and Yost recognized the therapeutic potential of nNIF. “We knew we were onto something that could be very meaningful,” recalls Yost.

To test if this cord blood-based factor could control sepsis, Zimmerman and Yost and others treated groups of mice that suffered from laboratory-induced inflammatory disease. In the absence of treatment, only 20 percent of the mice survived longer than two to four days. However, 60% of those mice treated with nNIF survived after the same amount of time.

“Sepsis is a case where the body’s reaction to infection is lethal,” says Yost. “nNIF is offering insights into how to keep the inflammatory response within prescribed limits.” He adds that they will carry out additional studies to test the therapeutic properties of nNIF.

Anti-Inflammatory Agent Isolated From Umbilical Cord Blood Infection fighting cells from umbilical cord blood (left) and circulating blood three days after birth (right) from the same prematurely born baby. Umbilical cord blood has high levels of a factor, called neonatal NET inhibitory factor (nNIF), which inhibits a specific inflammatory response called NETs. Within two weeks after birth, nNIF levels drop and NETs can form. True to their name, they consist of a net-like substance that traps infectious agents like bacteria, as seen on the right. nNIF is showing promise as a potential therapy against harmful inflammation and sepsis.
Anti-Inflammatory Agent Isolated From Umbilical Cord Blood
Infection fighting cells from umbilical cord blood (left) and circulating blood three days after birth (right) from the same prematurely born baby. Umbilical cord blood has high levels of a factor, called neonatal NET inhibitory factor (nNIF), which inhibits a specific inflammatory response called NETs. Within two weeks after birth, nNIF levels drop and NETs can form. True to their name, they consist of a net-like substance that traps infectious agents like bacteria, as seen on the right. nNIF is showing promise as a potential therapy against harmful inflammation and sepsis.

nNIF seems to be present for just a brief window of time at the beginning of life. It circulates in cord blood and persists in the baby’s own bloodstream for up to two weeks after birth. However, after two weeks, nNIF disappears and is not found in older babies and is completely absent from the blood of adults. Scientists in Yost’s laboratory also discovered that the placenta also contains a similar, albeit less potent, anti-inflammatory agent. The evanescent nature of these factors possibly indicates that inflammation is under tight control during this time, since the fragility of young babies might make extensive amounts of inflammation deleterious to their health.

“The beginning of life is a delicate balance,” says Yost. “Our work is showing that it is important to have the right defenses, but they have to be controlled.”

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mburatov

Professor of Biochemistry at Spring Arbor University (SAU) in Spring Arbor, MI. Have been at SAU since 1999. Author of The Stem Cell Epistles. Before that I was a postdoctoral research fellow at the University of Pennsylvania in Philadelphia, PA (1997-1999), and Sussex University, Falmer, UK (1994-1997). I studied Cell and Developmental Biology at UC Irvine (PhD 1994), and Microbiology at UC Davis (MA 1986, BS 1984).