ScienceDaily (Nov. 14, 2012) Environmental contaminants, such as smoking, are harmful to the human organism in relation to the occurrence of allergies. This is known. Until now, researchers had never investigated whether and to what extent environmental contaminants also affect allergy-relevant stem cells. For the first time a team at the Helmholtz Centre for Environmental Research (UFZ) has found evidence for this: Smoking affects the development of peripheral allergy-relevant stem cells in the blood. In order to present this result Dr. Irina Lehmann and Dr. Kristin Weie chose a new scientific path: The combination of exposure analysis and stem cell research.

Stem cells are not specialised, propagate without limit and can develop to different cell types. From these the different cell and tissue types of the human organism, including the allergy-promoting eosinophil granulocytes, are differentiated. Progenitor cells, e.g. eosinophil/basophilic progenitors, which mature in the bone marrow and are then washed out into the bloodstream -- the so-called periphery -- function as a link between unspecialised stem cells and specialised tissue and organ cells. Until now, whether and to what extent environmental contaminants affect this maturation and release has not been investigated.

The UFZ team of Dr. Irina Lehmann and Dr. Kristin Weie undertook their investigations from this point. Two facts were already known from a number of earlier studies: Firstly that the blood of allergy sufferers -- whether children or adults -- shows evidence of increased eosinophil/basophil progenitor levels. Secondly, that the occurrence of such peripheral progenitors in the blood of the umbilical cord indicates a higher risk for subsequent allergies. For the first time, the hypothesis which Dr. Kristin Weie and Dr. Irina Lehmann developed on this basis combined this knowledge from stem cell research with the results of many years of exposure research at the UFZ. The researchers characterise their approach in the following way: "We wanted to clarify the relationship between environmental influences and the maturation and differentiation of the progenitor cells on the one hand and its contribution to the occurrence of allergies on the other hand. Specifically, we wanted to know whether the occurrence of allergy-relevant progenitor cells in the blood of infants can be changed by environmental influences."

The results of the study, based on the data collected from 60 children aged one year, were recently published in the British medical journal "Clinical & Experimental Allergy": It was found that children with skin manifestations, such as atopic dermatitis or cradle cap, have increased levels of eosinophil progenitors in their blood. In this connection, it was shown for the first time that children already afflicted show particularly sensitive reactions when exposed to environmental contaminants: The offspring of families exposed to significant levels of volatile organic compounds (VOC) at home were found to have considerably higher allergy-relevant eosinophilic/basophilic progenitor cell levels. "That VOCs, large amounts of which are released with cigarette smoke, have the greatest effect on stem cells was not entirely unexpected," explains Dr. Irina Lehmann. "Just as important, however," adds Dr. Kristin Weie, is "that we can show that alterations in the number of stem cells as a result of harmful substances take place only in children who have already been afflicted with skin manifestations." This leads to the conclusion: There is a relationship between the genetic predisposition for a disease and environmental influences -- there are environmental and life style factors which determine whether a genetic predisposition is in fact realised or not.

Considerable logistical effort underlies this knowledge: On the one hand there is the long-term study "LiNA -- Life Style and Environmental Factors and their Influence on The Risk of Allergy" in Newborn Children, a joint project of the Helmholtz Centre for Environmental Research and the Stdtisches Klinikum St. Georg in Leipzig. 622 mothers, with a total of 629 children born, were recruited for the study between 2006 and 2008. In order to also take prenatal environmental influences into account -- in contrast with earlier comparable studies of newborn children -- mothers were already included in the investigations during pregnancy and the children from the time of birth. At the same time, it was necessary to become familiar with the methods required for stem cell analysis at the laboratory of the Canadian cooperation partner, Professor Judah Denburg of the McMaster University in Hamilton and to transfer this knowledge to Germany. Dr. Kristin Weie spent six months in Canada working in the group of Professor Denburg in order to acquire the necessary know-how and profit from the experience of the Canadian partners. Dr. Lehmann and Dr. Weie agree that "with the subject of environmental contamination and stem cells we have established an exciting new field of research." The UFZ team is currently the only one in the world investigating this relationship with analytical precision and methodical patience. The LiNA study, in the course of which mothers and their children can be observed over several years, represents a unique basis.

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Smoking affects allergy-relevant stem cells

Northern White Rhinoceros. Credit: San Diego Zoo

Starting with normal skin cells, scientists from The Scripps Research Institute have produced the first stem cells from endangered species. Such cells could eventually make it possible to improve reproduction and genetic diversity for some species, possibly saving them from extinction, or to bolster the health of endangered animals in captivity.

A description of the accomplishment appeared in an advance online edition of the journal Nature Methods on September 4, 2011.

Genesis

About five years ago, Oliver Ryder, PhD, the director of genetics at the San Diego Zoo Institute for Conservation Research, contacted Jeanne Loring, PhD, professor of developmental neurobiology at Scripps Research, to discuss the possibility of collecting stem cells from endangered species. Ryder's team had already established the Frozen Zoo, a bank of skin cells and other materials from more than 800 species and wondered if the thousands of samples they had amassed might be used as starting points.

Just as is hoped with humans, Ryder thought stem cells from endangered species might enable lifesaving medical therapies or offer the potential to preserve or expand genetic diversity by offering new reproduction possibilities.

At the time, although researchers were working with stem cells from embryos, scientists had not yet developed techniques for reliably inducing normal adult cells to become stem cells. But the technology arrived soon after, and scientists now accomplish this feat, called induced pluripotency, by inserting genes in normal cells that spark the transformation.

While Loring's team met with Ryder in early 2008, they realized that these newly emerging techniques might be applied to endangered species. Postdoctoral fellow Inbar Friedrich Ben-Nun, PhD, set out to systematically explore the possibilities.

Ryder suggested two species for initial work. The first was a highly endangered primate called a drill that he chose because of its close genetic connection to humans, and because in captivity the animals often suffer from diabetes, which researchers are working to treat in humans using stem cell-based therapies.

The northern white rhinoceros was the second candidate. Ryder chose this animal because it is genetically far removed from primates, and because it is one of the most endangered species on the planet. There are only seven animals still in existence, two of which reside at the San Diego Zoo Safari Park.

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Scientists produce first stem cells from endangered species

Dead and damaged heart muscle may be replaced with stem cells from the heart itself, if a new chemical discovered by La Jolla-based scientists lives up to its promise.

The chemical, called IDT-1, turns mouse and human embryonic stem cells into an unlimited number of heart muscle cells, called cardiomyocytes. The scientists say it might yield a drug to repair damage from heart attacks and from cardiac fibrosis, or scarring in heart tissue.

A study on the findings was published Nov. 6 in the Journal of Medicinal Chemistry. Its authors include Dennis Schade and John Cashman of the Human BioMolecular Institute, along with Mark Mercola of the Sanford-Burnham Medical Research Institute.

The three are working with ChemRegen, a private La Jolla biotech company established by Cashman and colleagues, to see if a drug can be produced from the research.

If such a drug does emerge, it could become a blockbuster. Heart disease was the leading cause of death in the United States last year, with nearly 600,000 deaths, according to the U.S Centers for Disease Control and Prevention in Atlanta.

Hearts contain their own stem cells. While these cells could repair the damage from a heart attack, they don't, Cashman said.

"They need to be stimulated," he said. "They need to have a good reason to turn into heart cells."

The IDT-1 chemical blocks the activity of a substance called transforming growth factor-beta usually present in stem cells. This lack of activity starts the stem cells down the road into becoming heart cells.

But before ChemRegen can start clinical trials on a drug based on IDT-1, it must be tested for toxicity and taken through animal studies to see if it provides therapeutic benefit," Cashman said. All told, that may cost about $3 million to $4 million, with $1 million going for toxicology studies and the rest for animal studies. ChemRegen plans to seek partnerships with drug companies or other investors to fund that work.

IDT-1 is what the drug industry calls a small molecule, which has a relatively simple structure. In contrast, biotech products often are made up of large protein molecules, DNA, or even whole cells. Cashman said having a small molecule to work with should be a plus for pharmaceutical companies, because they're experienced in making such drugs.

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New chemical may spur heart repair