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News from Ukraine about fullerenes in nanomedicine!!!

Science, Research & Technology
News from Ukraine about fullerenes in nanomedicine!!!

Grigoriy Andrievsky
Director of Science, PhD. at "Institute of Physiological Active Compounds" LLC
To:Walter Derzko, […]

Dear sir/madam,
Dear colleagues,

After many years of scientific research and extended preclinical and clinical trials, at the end of 2010 in Ukraine, for the first time in the world, the following products “Concentrated solutions of hydrated С60 fullerene” (C60FWS), “Water with hydrated С60 fullerene” and fully highly purified С60 fullerene were approved by the Ministry of Health of Ukraine for use as a component in food products and cosmetics. This includes their administration as a multifunctional dietary supplement, which has unique medicinal and preventive properties while, at the same time, being absolutely safe for humans.

You may find this same information upon visiting our site http://www.ipacom.com, in particular via the following links: http://www.ipacom.com/index.php/ru/products-left/68 and
http://www.ipacom.com/index.php/ru/products
http://ipacom.com/index.php/en/fullerenes-and-water-left/74
http://ipacom.com/index.php/en/publications-about-c60hyfn/70
http://ipacom.com/images/Articles/annotation_en.pdf

In addition, you may see our News and obtain the file of presentation: “About the most important physical, chemical and biological properties of hydrated С60 fullerene (С60HyFn) and its water solutions (С60FWS)” on our site:
http://ipacom.com/index.php/en/publications-about-c60hyfn/92

Thus, the water solutions of hydrated fullerene С60 have already become available commercially and they can now be purchased for your own research and applications in many areas of human activity and, especially, as optimum means for preventive medicine of the future.

Thank you very much in advance.

On behalf of my colleagues,

Grigoriy Andrievsky

Director of Science, PhD.
Institute of Physiological Active Compounds, LLC.
58, Lenin ave.,
61072, Kharkov,
Ukraine
Phone: +38 057 763 0521 (Phone/Fax, Office)
+38 057 763 0336 (Lab.)
E-mail: yard@kharkov.ua or
science@ipacom.com
http://www.ipacom.com (russ./engl.)

Dentistry breakthought- Filling without drilling

Researchers at the University of Leeds have discovered a pain-free way of tackling dental decay that reverses the damage of acid attack and re-builds teeth as new.

The pioneering treatment promises to transform the approach to filling teeth forever.

Tooth decay begins when acid produced by bacteria in plaque dissolves the mineral in the teeth, causing microscopic holes or 'pores' to form. As the decay process progresses these micro-pores increase in size and number. Eventually the damaged tooth may have to be drilled and filled to prevent toothache, or even removed.

The very thought of drilling puts many people off going to see their dentist, whether or not they actually need treatment. This tendency to miss check-ups and ignore niggling aches and pains means that existing problems get worse and early signs of decay in other teeth are overlooked.

It's a vicious cycle, but one that can be broken, according to researchers at the University of Leeds who have developed a revolutionary new way to treat the first signs of tooth decay. Their solution is to arm dentists with a peptide-based fluid that is literally painted onto the tooth's surface. The peptide technology is based on knowledge of how the tooth forms in the first place and stimulates regeneration of the tooth defect.

"This may sound too good to be true, but we are essentially helping acid-damaged teeth to regenerate themselves. It is a totally natural non-surgical repair process and is entirely pain-free too," said Professor Jennifer Kirkham, from the University of Leeds Dental Institute, who has led development of the new technique.

The 'magic' fluid was designed by researchers in the University of Leeds' School of Chemistry, led by Dr Amalia Aggeli. It contains a peptide known as P 11-4 that - under certain conditions - will assemble together into fibres. In practice, this means that when applied to the tooth, the fluid seeps into the micro-pores caused by acid attack and then spontaneously forms a gel. This gel then provides a 'scaffold' or framework that attracts calcium and regenerates the tooth's mineral from within, providing a natural and pain-free repair.

The technique was recently taken out of the laboratory and tested on a small group of adults whose dentist had spotted the initial signs of tooth decay. The results from this small trial have shown that P 11-4 can indeed reverse the damage and regenerate the tooth tissue.

"The results of our tests so far are extremely promising," said Professor Paul Brunton, who is overseeing the patient testing at the University of Leeds Dental Institute. "If these results can be repeated on a larger patient group, then I have no doubt whatsoever that in two to three years time this technique will be available for dentists to use in their daily practice."

"The main reason that people don't go to the dentist regularly is fear. If we can offer a treatment that is completely non-invasive, that doesn't involve a mechanical drill, then we can change that perceived link between dental treatment and pain. This really is more than filling without drilling, this is a novel approach that enables the patients to keep their natural teeth!"

 

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The study is being funded by credentis ag who have licensed the technology and are preparing to introduce P11-4 to dentists worldwide.

Contact: Paula Gould
p.a.gould@leeds.ac.uk
44-113-343-8059
University of Leeds

Why does stress causes DNA damage?

DURHAM, N.C. – For years, researchers have published papers that associate chronic stress with chromosomal damage.

Now researchers at Duke University Medical Center have discovered a mechanism that helps to explain the stress response in terms of DNA damage.

"We believe this paper is the first to propose a specific mechanism through which a hallmark of chronic stress, elevated adrenaline, could eventually cause DNA damage that is detectable," said senior author Robert J. Lefkowitz, M.D., James B. Duke Professor of Medicine and Biochemistry and a Howard Hughes Medical Institute (HHMI) investigator at Duke University Medical Center.

The paper was published in the Aug. 21 online issue of Nature.

In the study, mice were infused with an adrenaline-like compound that works through a receptor called the beta adrenergic receptor that Lefkowitz has studied for many years. The scientists found that this model of chronic stress triggered certain biological pathways that ultimately resulted in accumulation of DNA damage.

"This could give us a plausible explanation of how chronic stress may lead to a variety of human conditions and disorders, which range from merely cosmetic, like graying hair, to life-threatening disorders like malignancies," Lefkowitz said.

P53 is a tumor suppressor protein and is considered a "guardian of the genome" – one that prevents genomic abnormalities.

"The study showed that chronic stress leads to prolonged lowering of p53 levels," said Makoto Hara, Ph.D., a postdoctoral fellow in the Lefkowitz laboratory. "We hypothesize that this is the reason for the chromosomal irregularities we found in these chronically stressed mice."

Lefkowitz earlier had proved the existence of isolated, and characterized the G-protein-coupled receptors (GPCRs) such as the beta adrenergic receptor. These receptors, which are located on the surface of the membranes that surround cells, are the targets of almost half of the drugs on the market today, including beta blockers for heart disease, antihistamines and ulcer medications.

Now he is continuing studies along another pathway,stemming from the GPCRs, that was discovered in his lab, which is known as the beta-arrestin pathway. At first, the theory was that beta-arrestin proteins turned off or desensitized the G-protein pathways, but evidence is accumulating that these proteins are also responsible for causing certain biochemical activities in their own right.

In the current study, the scientists found a molecular mechanism through which adrenaline-like compounds acted through both G-protein and the beta-arrestin pathways to trigger DNA damage.

The Nature publication showed that the infusion of an adrenaline-like compound for four weeks in the mice caused degradation of p53, which was present in lower levels over time.

The study also showed that the DNA damage was prevented in mice lacking beta-arrestin 1. Loss of beta-arrestin 1 stabilized cellular levels of p53 both in the thymus, an organ that strongly responds to acute or chronic stress, and in the testes, where paternal stress might affect an offspring's genome.

Future studies planned by the Lefkowitz laboratory include studying mice that are placed under stress (restrained), thus creating their own adrenaline or stress reaction to learn whether the physical reactions of stress, rather than an influx of adrenaline in the lab as was done in the current study, also leads to accumulation of DNA damage.

 

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Other authors include Jeffrey J. Kovacs, Erin J. Whalen, Sudarshan Rajagopal, Ryan T. Strachan, Seungkirl Ahn, Barbara Williams, Christopher M. Lam, Kunhong Xiao, and Sudha K. Shenoy, all of the Duke Department of Medicine; Aaron J. Towers and Simon G. Gregory of the Department of Medicine and the Center for Human Genetics at Duke; and Wayne Grant and Derek R. Duckett of the Translational Research Institute, The Scripps Research Institute, Jupiter, Fla..

The study was supported by the Howard Hughes Medical Institute.

Quantum Biology

Physics of life: The dawn of quantum biology  (hat tip to Steve Kurtz)

The key to practical quantum computing and high-efficiency solar cells may lie in the messy green world outside the physics lab.

On the face of it, quantum effects and living organisms seem to occupy utterly different realms. The former are usually observed only on the nanometre scale, surrounded by hard vacuum, ultra-low temperatures and a tightly controlled laboratory environment. The latter inhabit a macroscopic world that is warm, messy and anything but controlled. A quantum phenomenon such as 'coherence', in which the wave patterns of every part of a system stay in step, wouldn't last a microsecond in the tumultuous realm of the cell.

Or so everyone thought. But discoveries in recent years suggest that nature knows a few tricks that physicists don't: coherent quantum processes may well be ubiquitous in the natural world.

and:

Robert Blankenship, a photosynthesis researcher at Washington University in St Louis, Missouri, and a co-author with Fleming on the C. tepidium paper, admits to some scepticism. "My sense is that there may well be a few cases, like the ones we know about already, where these effects are important," he says, "but that many, if not most, biological systems will not utilize quantum effects like these." But Scholes believes that there are grounds for optimism, given a suitably broad definition of quantum biology. "I do think there are other examples in biology where an understanding at the quantum-mechanical level will help us to appreciate more deeply how the process works," he says.

and:

Quantum coherence in photosynthesis seems to be beneficial to the organisms using it. But did their ability to exploit quantum effects evolve through natural selection? Or is quantum coherence just an accidental side effect of the way certain molecules are structured? "There is a lot of speculation about the evolutionary question, and a lot of misunderstanding," says Scholes, who is far from sure about the answer. "We cannot tell if this effect in photosynthesis is selected for, nor if there is the option not to use coherence to move the electronic energy. There are no data available at all even to address the question."

More: http://www.nature.com/news/2011/110615/full/474272a.html

Higher vitamin D intake needed to reduce cancer risk- 4000-8000 IU per day

[N.B....Vitaman D the Sunshine Vitamin....Coincidently cancer rates started to increase in the world as fewer and fewer people worked outdoors as farmers--higher  cancer rates in northern climates then at the equator --wd]

Researchers at the University of California, San Diego School of Medicine and Creighton University School of Medicine in Omaha have reported that markedly higher intake of vitamin D is needed to reach blood levels that can prevent or markedly cut the incidence of breast cancer and several other major diseases than had been originally thought. The findings are published February 21 in the journal Anticancer Research

While these levels are higher than traditional intakes, they are largely in a range deemed safe for daily use in a December 2010 report from the National Academy of Sciences Institute of Medicine.

"We found that daily intakes of vitamin D by adults in the range of 4000-8000 IU are needed to maintain blood levels of vitamin D metabolites in the range needed to reduce by about half the risk of several diseases - breast cancer, colon cancer, multiple sclerosis, and type 1 diabetes," said Cedric Garland, DrPH, professor of family and preventive medicine at UC San Diego Moores Cancer Center. "I was surprised to find that the intakes required to maintain vitamin D status for disease prevention were so high – much higher than the minimal intake of vitamin D of 400 IU/day that was needed to defeat rickets in the 20th century."

"I was not surprised by this" said Robert P. Heaney, MD, of Creighton University, a distinguished biomedical scientist who has studied vitamin D need for several decades. "This result was what our dose-response studies predicted, but it took a study such as this, of people leading their everyday lives, to confirm it."

The study reports on a survey of several thousand volunteers who were taking vitamin D supplements in the dosage range from 1000 to 10,000 IU/day. Blood studies were conducted to determine the level of 25-vitamin D – the form in which almost all vitamin D circulates in the blood.

"Most scientists who are actively working with vitamin D now believe that 40 to 60 ng/ml is the appropriate target concentration of 25-vitamin D in the blood for preventing the major vitamin D-deficiency related diseases, and have joined in a letter on this topic," said Garland. "Unfortunately, according a recent National Health and Nutrition Examination Survey, only 10 percent of the US population has levels in this range, mainly people who work outdoors."

Interest in larger doses was spurred in December of last year, when a National Academy of Sciences Institute of Medicine committee identified 4000 IU/day of vitamin D as safe for every day use by adults and children nine years and older, with intakes in the range of 1000-3000 IU/day for infants and children through age eight years old.

While the IOM committee states that 4000 IU/day is a safe dosage, the recommended minimum daily intake is only 600 IU/day.

"Now that the results of this study are in, it will become common for almost every adult to take 4000 IU/day," Garland said. "This is comfortably under the 10,000 IU/day that the IOM Committee Report considers as the lower limit of risk, and the benefits are substantial." He added that people who may have contraindications should discuss their vitamin D needs with their family doctor.

"Now is the time for virtually everyone to take more vitamin D to help prevent some major types of cancer, several other serious illnesses, and fractures," said Heaney.

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Other co-authors of the article were Leo Baggerly, PhD, and Christine French.

More facts are available from Anticancer Research: www.GrassrootsHealth.net; and the National Academy of Sciences - Institute of Medicine: www.iom.edu/Reports/2010/Dietary-Reference-Intakes-for-Calcium-and-Vitamin-D.aspx

Changes in brain circuitry play role in moral sensitivity as people grow up

People's moral responses to similar situations change as they age, according to a new study at the University of Chicago that combined brain scanning, eye-tracking and behavioral measures to understand how the brain responds to morally laden scenarios.

Both preschool children and adults distinguish between damage done either intentionally or accidently when assessing whether a perpetrator had done something wrong. Nonetheless, adults are much less likely than children to think someone should be punished for damaging an object, especially if the action was accidental, said study author Jean Decety, the Irving B. Harris Professor in Psychology and Psychiatry at the University of Chicago and a leading scholar on affective and social neuroscience.

The different responses correlate with the various stages of development, Decety said, as the brain becomes better equipped to make reasoned judgments and integrate an understanding of the mental states of others with the outcome of their actions. Negative emotions alert people to the moral nature of a situation by bringing on discomfort that can precede moral judgment, and such an emotional response is stronger in young children, he explained.

"This is the first study to examine brain and behavior relationships in response to moral and non-moral situations from a neurodevelopmental perspective," wrote Decety in the article, "The Contribution of Emotion and Cognition to Moral Sensitivity: A Neurodevelopmental Study," published in the journal Cerebral Cortex. The study provides strong evidence that moral reasoning involves a complex integration between affective and cognitive processes that gradually changes with age.

For the research, Decety and colleagues studied 127 participants, aged 4 to 36, who were shown short video clips while undergoing an fMRI scan. The team also measured changes in the dilation of the people's pupils as they watched the clips.

The participants watched a total of 96 clips that portrayed intentional harm, such as someone being shoved, and accidental harm, such as someone being struck accidentally, such as a golf player swinging a club. The clips also showed intentional damage to objects, such as a person kicking a bicycle tire, and accidental damage, such as a person knocking a teapot off the shelf.

Eye tracking in the scanner revealed that all of the participants, irrespective of their age, paid more attention to people being harmed and to objects being damaged than they did to the perpetrators. Additionally, an analysis of pupil size showed that "pupil dilation was significantly greater for intentional actions than accidental actions, and this difference was constant across age, and correlated with activity in the amygdala and anterior cingulate cortex," Decety said.

The study revealed that the extent of activation in different areas of the brain as participants were exposed to the morally laden videos changed with age. For young children, the amygdala, which is associated the generation of emotional responses to a social situation, was much more activated than it was in adults.

In contrast, adults' responses were highest in the dorsolateral and ventromedial prefrontal cortex — areas of the brain that allow people to reflect on the values linked to outcomes and actions.

In addition to viewing the video clips, participants were asked to determine, for instance, how mean was the perpetrator, and how much punishment should he receive for causing damage or injury. The responses showed a clear connection between moral judgments and the activation the team had observed in the brain.

"Whereas young children had a tendency to consider all the perpetrator malicious, irrespective of intention and targets (people and objects), as participants aged, they perceived the perpetrator as clearly less mean when carrying out an accidental action, and even more so when the target was an object," Decety said.

When recommending punishments, adults were more likely to make allowances for actions that were accidental, he said. The response showed that they had a better developed prefrontal cortex and stronger functional connectivity between this region and the amygdala than children. Adults were better equipped to make moral judgments. "In addition, the ratings of empathic sadness for the victim, which were strongest in young children, decreased gradually with age, and correlated with the activity in the insula and subgenual prefrontal cortex," which area areas associated with emotional behavior and automatic response to stresses, Decety said. Together, the results are consistent with the view that morality is instantiated by functionally integrating several distributed areas/networks.

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The research was supported with a grant from the National Science Foundation. Joining Decety in writing the paper were Kalina Michalska, a postdoctoral scholar, and Katherine Kinzler, an assistant professor, both in the Department of Psychology.

 

Five ‘hot spots’ where medicine and technology are converging

Medicine and technology are converging at a faster pace than most people realize, says New Jersey Institute of Technology Professor Atam Dhawan, chair of the the IEEE emerging technology committee.

Here are the five “hot spots” of convergence identified by Professor Dhawan:

Point of care health care technologies — connecting patients with healthcare professionals via computers.  This includes nursing engineering, health monitoring, e-health, and health care information management for disaster situations.

Optical imaging technologies — diagnosing and staging cancer, cardiovascular diseases, and other fibrotic diseases. This includes discovery and exploration of naturally existing molecular targets of diseases and the differences associated with the molecular targets between normal and diseased states, as well as diagnosis and treatment.

Bioelectronics, bio-nano-sensor technology, and neural engineering — increased knowledge of the nervous system, neurophysiology, and neurological disorders as well as the development of devices to interface with neural tissues.

Tissue engineering and regenerative medicine — the advent of stem cell-based therapies, regenerative medicine, and gene therapy.

Medical or bio-robots — nano, micro, and macro devices to assist in diagnosis, surgery, prosthetics, rehabilitation and personal assistance. This includes clinical, therapeutic, and surgical applications of medical robots with advanced instrumentation, sensors, actuators, and real-time systems.

Professor Dhawan prepared his comments as workshop chair for the upcoming 33rd IEEE Engineering in Medicine and Biology Society (EMBS) Annual International Conference.

Stomach bacteria impact brain chemistry and behavior

‘That gut feeling’: how stomach bacteria impact brain chemistry and behavior

Experiments with mice have determined that behavior and brain chemistry varies depending on the type of bacteria in the gut, report Stephen Collins at McMaster University and Premysl Bercik at the Farncombe Family Digestive Health Research Institute.

Working with healthy adult mice, the researchers showed that disrupting the normal bacterial content of the gut with antibiotics produced changes in behavior; the mice became either anxious or less cautious. This change was accompanied by an increase in brain-derived neurotrophic factor (BDNF), which has been linked to depression and anxiety.

When oral antibiotics were discontinued, bacteria in the gut returned to normal, “accompanied by restoration of normal behavior and brain chemistry,” Collins said.

The findings are important because several common types of gastrointestinal disease, including irritable bowel syndrome, are frequently associated with anxiety or depression. In addition there has been speculation that some psychiatric disorders, such as late onset autism, may be associated with an abnormal bacterial content in the gut.

Bercik suggested that these results lay the foundation for investigating the therapeutic potential of probiotic bacteria and their products in the treatment of behavioral disorders, particularly those associated with gastrointestinal conditions such as irritable bowel syndrome.

The research appears in the online edition of the journal Gastroenterology.

Gut bacteria and stress

Another recent study with mice has also demonstrated a connection between gut bacteria in the digestive system and stress response.

Researchers at Ohio State University showed that gut bacterial colonies in mice decrease and immune biomarkers increase in response to stress. They ran a series of experiments using an aggressive mouse as a stressor for docile mice.

At the end of the stress experiments, blood samples and material from inside each animal’s intestine were taken from stressed animals along with samples from a control group. The blood samples were analyzed to detect the levels of two immune biomarkers used to gauge stress: a cell-signalling cytokine molecule and a protein called MCP-1 that summons macrophages, or scavenger cells, to the site of an infection.

The intestinal samples were used to determine the relative proportion of at least 30 types of bacteria residing there.

Compared to the control mice, the stressed animals showed two marked differences: the proportion of one important type of bacteria in the gut (Bacteroides) fell by 20 to 25 percent while another type (Clostridium) increased a similar amount. Also, levels of the two biomarkers jumped 10-fold in the stressed mice, compared to controls.

The researchers concluded that exposure to social stressors “significantly affect gut bacterial populations” while increasing circulating cytokines that regulate inflammatory responses.

Ref.: Bailey MT et al., Exposure to a social stressor alters the structure of the intestinal microbiota: implications for stressor-induced immunomodulation, Brain, Behavior, and Immunity, 2011

Antiviral protein design - Scientists design new anti-flu virus proteins using computational methods

One goal of antiviral protein design is to block molecular mechanisms involved in cell invasion and virus reproduction

A research article May 12 in Science demonstrates the use of computational methods to design new antiviral proteins not found in nature, but capable of targeting specific surfaces of flu virus molecules.

One goal of such protein design would be to block molecular mechanisms involved in cell invasion and virus reproduction.

Computationally designed, surface targeting, antiviral proteins might also have diagnostic and therapeutic potential in identifying and fighting viral infections.

The lead authors of the study are Sarel J. Fleishman and Timothy Whitehead of the University of Washington (UW) Department of Biochemistry, and Damian C. Ekiert from the Department of Molecular Biology and the Skaggs Institute for Chemical Biology at The Scripps Research Institute. The senior authors are Ian Wilson from Scripps and David Baker from the UW and the Howard Hughes Medical Institute.

The researchers note that additional studies are required to see if such designed proteins can help in diagnosing, preventing or treating viral illness. What the study does suggest is the feasibility of using computer design to create new proteins with antiviral properties.

"Influenza presents a serious public health challenge," the researchers noted, "and new therapies are needed to combat viruses that are resistant to existing anti-viral medications or that escape the body's defense systems."

They focused their attention on the section of the flu virus known as the hemagglutinin stem region. They concentrated on trying to disable this part because of its function in invading the cells of the human respiratory tract.

Their approach was somewhat similar to engineering a small space shuttle with the right configuration and construction, as well as recognizance and interlocking mechanisms, to dock with a troublesome space station and upset its mission. Only these scientists attempted their engineering feat at an atomic and molecular level.

Central to their approach is the ability of biological molecules to recognize certain other molecules or their working parts, and to have an affinity for binding to them at pre-determined locations. This recognition has both physical and chemical bases. Protein-protein interactions underlie many biological activities, including those that disarm and deactivate viruses.

In their report, the researchers described their general computational methods for designing new, tiny protein molecules that could bind to a certain spot on large protein molecules. They took apart some protein structures and watched how these disembodied sections interacted with a target surface. They analyzed particular high-affinity interactions, and used this information to further refine computer-generated designs for interfaces.

"Protein surfaces are never flat, but have many crevices and bulges at the atomic scale," lead author Sarel Fleishman explained. "The challenge is to identify amino acid side chains that would fit perfectly into these surfaces. The fit must be precise both in shape and in other chemical properties such as electrostatic charge. This geometrical and biophysical problem can be computationally solved, but requires large computational resources."

The researchers made use of a peer-to-peer computing platform called Rosetta@Home for going through the hundreds of millions of possible interactions of designed proteins and the surface of hemagglutinin to solve this challenge.

Following optimization, the designed proteins bound hemagglutinin very tightly.

Through this method, the researchers created two designs for new proteins that could bind to a surface patch on the stem of the influenza hemagglutinin from the 1918 H1N1 pandemic flu virus.

The shortcomings of the approach, due to approximations, meant that the researchers started out with 73 possibilities of which just two were successful.

One of the disease-causing characteristics of the influenza hemagglutinin stem is that it changes shape by refolding when in an acidic environment. This reconfiguration appears to allow the virus reproduce itself inside of cells.

In this study, one of the newly designed proteins was shown to block a conformational change, not only in H1 influenza hemagglutinin, but also in a similar component in H5 avian influenza.

"This finding suggests that this new protein design may have virus-neutralizing effects against multiple influenza subtypes," the researchers reported.

What was unusual about the workable designs was that they had helical binding modes, roughly shaped like a spiral staircase, rather than the loop binding that naturally occurring antibodies employ.

X-ray crystallography of the proteins complex showed that the actual orientation of the bound proteins was almost identical to the way the binding mode was designed. The modified surface of the main recognition helix on the designed protein was packed into a groove on the desired region of the virus protein.

"Overall, the crystal structure is in excellent agreement with the designed interface," the researchers noted, "with no significant deviations at any of the contact points." The design and the actual formation were nearly identical.

The scientists were encouraged by this finding. Despite their limitations, the design methods, the scientists believe, capture the essential features of the desired protein-protein interaction.

http://www.eurekalert.org/pub_releases/2011-05/uow-sdn051311.php

 

Walter Derzko

Smart Economy

Toronto

Study finds therapies using induced pluripotent stem cells could encounter immune rejection problems

Biologists at UC San Diego have discovered that an important class of stem cells known as "induced pluripotent stem cells," or iPSCs, derived from an individual's own cells, could face immune rejection problems if they are used in future stem cell therapies.

In today's advance online issue of the journal Nature, the researchers report the first clear evidence of immune system rejection of cells derived from autologous iPSCs that can be differentiated into a wide variety of cell types.

Because iPSCs are not derived from embryonic tissue and are not subject to the federal restrictions that limit the use of embryonic stem cells, researchers regard them as a promising means to develop stem cell therapies. And because iPSCs are derived from an individual's own cells, many scientists had assumed that these stem cells would not be recognized by the immune system. As a consequence, the immune system would not try to mount an attack to purge them from the body.

In fact, scientists regarded iPSCs as particularly attractive candidates for clinical use because cells derived from embryonic stem cells will induce immune system rejection that requires physicians to administer immune suppressant medications that can compromise a person's overall health.

But the UCSD biologists, funded by NIH and an early translational grant from the California Institute for Regenerative Medicine, the state's stem-cell funding agency, found that iPSCs are subject to some of the same problems of immune system rejection as embryonic stem cells.

"The assumption that cells derived from iPSCs are totally immune tolerant has to be reevaluated before considering human trials," says Yang Xu, a professor of biology at UCSD who headed the team that published the study.

His team of biologists—which included postdoctoral researchers Tongbiao Zhao, Zhen-Ning Zhang and Zhili Rong—reached that conclusion after testing the immune response of an inbred strain of mice to embryonic stem cells and several types of iPSCs derived from the same strain of inbred mice.

The scientists found, not surprisingly, that the immune system of one mouse could not recognize the cells derived from embryonic stem cells of the same strain of mice. But the experiments also showed that the immune system rejected cells derived from iPSCs reprogrammed from fibroblasts of the same strain of mice, mimicking the situation whereby a patient would be treated with cells derived from iPSCs reprogrammed from the patient's own cells. The scientists also found that the abnormal gene expression during the differentiation of iPSCs causes the immune responses.

"This result doesn't suggest that iPSCs cannot be used clinically," says Xu. "It is important now to look at exactly what types of cells derived from iPSCs—and there probably are not that many based on our findings—are likely to generate immune system rejection."

"Our immune response assay is a robust method for checking the immune tolerance, and therefore, the safety of iPSC that may be developed," he added.

With grants from the California Institute for Regenerative Medicine, Xu's team is also developing strategies to minimize the formation of tumors that result from the use of human embryonic stem cells and to increase the immune tolerance of human embryonic stem cells.