Fraunhofer Institute for Cell Therapy and Immunology


Fraunhofer Institute for Cell Therapy and Immunology

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News Article | February 15, 2017

Primitive plants are the latest forms of Earth life to show they can survive in the harshness of space, and for many months. Cold-loving algae from the Arctic Circle have joined the space-travelling club, alongside bacteria, lichens and even simple animals called tardigrades. Preliminary studies of the algae after their return to Earth from the International Space Station lend some weight to the “panspermia” theory, that comets and meteorites could potentially deliver life to otherwise sterile planets. The results also provide insights into the potential for human colonies on distant planets to grow crops brought from Earth. The algae were a species of Sphaerocystis, codenamed CCCryo 101-99, and were returned to Earth in June last year after spending 530 days on a panel outside the ISS. While space-borne, they withstood the vacuum, temperatures ranging from -20 °C at night to 47.2 °C during the day, plus perpetual ultraviolet radiation of a strength that would destroy most life on Earth if not filtered out by the atmosphere. “I’m sure that plants of many kinds have been on the ISS before, but on the inside, not the outside,” says Thomas Leya of the Fraunhofer Institute for Cell Therapy and Immunology in Potsdam, Germany, who organised the algae experiment. “As far as I know, this is the first report of plants exposed on the surface of the space station.” It was Leya who discovered CCCryo 101-99 on Norway’s remote Svalbard peninsula. When dormant, these algae develop thick walls and become orange cysts rich in protective carotenoids, the substances that give carrots their colour. But when seasonal rains arrive, they rapidly resume making chlorophyll and turn green again. “If you give them water, the cysts germinate and revive,” says Leya. Leya chose CCCryo 101-99 for the space ordeal based on its ability to withstand extreme cold and drying out. To help the algae through, he dried them out beforehand and coaxed them into the dormant, cyst-like state where they simply ticked over, without reproducing, feeding or multiplying. All samples were open to space but overlaid with a transparent filter to reduce the radiation exposure (pictured, top). All but one sample survived. Preliminary results the institute released last week showed that within days of their return, all the algae bounced back to normal. “Within just two weeks they become green again,” says Leya. Team members at the Technical University in Berlin will now explore the extent of damage to the algal DNA, as this could give insights into the capacity of plants to survive and multiply away from Earth. Leya stresses that if future missions to colonise other planets aim to grow crops, the seeds would need to be carefully protected in transit inside spaceships, unlike the algae just back from the ISS. Likewise, crops grown at the destination would need to be carefully shielded from environmental harms. “These algae had been desiccated before they went into space, and during their time on the ISS they were kept dormant, with no growth, no development and almost no metabolism,” says René Demets of the European Space Agency. “But the experiment shows that some terrestrial organisms are robust enough to cope with months of exposure to open space conditions without a space suit.” Leya also sent up photosynthesising microbes called cyanobacteria, specifically a species discovered in Antarctica, and found that it survived. The work formed part of a bigger experiment called Biomex, led by Jean-Pierre Paul de Vera of the German Aerospace Centre in Berlin. It included mosses from the Alps, black microfungi from the Antarctic, desert lichens, and various bacteria.

News Article | February 15, 2017

In a long-term experiment on the International Space Station, Fraunhofer researchers studied how the extreme conditions in space affect algae. Fraunhofer conducted this experiment in close cooperation with German and international partners. Research findings could benefit industrial applications and perhaps a mission to Mars. They're alive! Two algae survived 16 months on the exterior of the International Space Station ISS despite extreme temperature fluctuations and the vacuum of space as well as considerable UV and cosmic radiation. That was the astonishing result of an experiment conducted by Dr. Thomas Leya at the Fraunhofer Institute for Cell Therapy and Immunology IZI in Potsdam in cooperation with German and international partners. This labor-intensive experiment was part of the large-scale Biology and Mars Experiment (BIOMEX), a project coordinated by Dr. Jean-Pierre de Vera at the German Aerospace Center (DLR) in Berlin. Dr. Leya himself had isolated the green algal strain CCCryo 101-99 of Sphaerocystis sp. on Svalbard, a Norwegian archipelago, and prepared it together with the cyanobacterium Nostoc sp. (CCCryo 231-06), a blue-green alga from Antarctica. CCCryo stands for Culture Collection of Cryophilic Algae. Nostoc sp. and Sphaerocystis sp. are examples of cold-loving, or cryophilic, strains. They have special adaptation strategies to oppose cold and desiccation, allowing them to survive even under extreme conditions. Dr. Leya heads the Extremophile Research & Biobank CCCryo Working Group at Fraunhofer's Bioanalytics and Bioprocesses IZI-BB branch in Potsdam. For the past 18 years, the group has been studying the survival strategies of cryophilic algae, cyanobacteria, mosses, fungi and bacteria found in polar regions. Researchers had already ascertained in the laboratory that algae are largely unsusceptible to long-term desiccaton stress, extreme temperatures or UV radiation. Yet the extreme conditions of near-Earth orbit cannot be fully simulated in labs. "We slightly desiccated the algal strains in preparation for their time in space," explains Dr. Leya. A Progress spacecraft transported the organisms into space on July 23, 2014, and a Soyuz capsule returned the algal cultures to Earth. All in all, they had to endure some 16 months on the outside of the ISS - with only neutral-density filters reducing the effects of radiation. Sensors measured and logged temperature changes and amounts of cosmic radiation. Researchers will now scrutinize the adaptation strategies of the blue and green algae. Because UV radiation can damage human DNA, the Technische Universität Berlin and the DLR are studying the DNA of the ISS algae to determine whether it was damaged and, if so, to what extent. They are also using spectroscopic techniques to analyze the biomarkers of carotenoids in the algae. Experts use the term "biomarker" to refer to any biomolecules and their measurable characteristics. These findings are significant in many ways - including a mission to Mars someday. The production of food on Mars would be essential for survival, should people colonize the Red Planet in the distant future. Algae produce oxygen and proteins, making them a good source of food; particularly hardy strains could be grown in special greenhouses or semitransparent tents. Researchers are also curious to know if, millions of years ago, organisms or early life forms from space perhaps gave rise to life on Earth. Early forms of life might have reached Earth via meteorites. This theory of panspermia, as it is known, might experience a revival thanks to the ISS algae experiments. Components of algae as nutritional supplements and sun protection Various industries will likewise benefit from the findings of the ISS algae experiment. Possibly cosmetics manufacturers will soon be able to manufacture UV-protection creams that contain components of algae. For the food industry, algae contain appealing nutritional supplements thanks to their efficient repair mechanisms and high content of omega-3 fatty acids such as eicosapentaenoic acid (EPA). Appropriate manufacturing methods are still very costly, but should become commercially viable in the near future. Dr. Leya has collected nearly 500 algal and other organisms in polar regions and other extreme localities worldwide. But experts believe that well over one hundred thousand species exist - of which only a fraction has been identified. This means chances are good that these underestimated organisms will provide another surprise or two.

Fricke S.,Fraunhofer Institute for Cell Therapy and Immunology
Methods in Molecular Biology | Year: 2011

A variety of stem cells, including embryonic, mesenchymal, and hematopoietic stem cells, have been isolated to date, resulting in the current investigation of many therapeutic applications. These stem cells offer a high potential in cell replacement therapies or in the regeneration of organ damage. One current obstacle in using these stem cells in clinical applications are the unknown or unexplained mechanisms regarding the activation of immune responses as well as their given potential of immune activity, which can attack the host tissue. Similarly, the unknown immunological environment, which can benefit tumor growth, also restrains the rapid clinical implementation of stem cells. We have shown that several techniques for measurement or illustration of immune responses in a hematopoietic murine CD4 k/o mice transplantation model might be beneficial to get new insight into in vivo behavior of transplanted stem cells. Subjected to the transplantation setups (allogeneic, syngeneic, or xenogenic transplantation) different immune responses (enhancement of CD4 + T cells, cytokine activity) as well as different effects of the transplanted cells on the host organs (organ destruction, toxicity) are detectable. The methods used to describe such immune responses will be presented here. © 2011 Springer Science+Business Media, LLC.

Hinze A.,Fraunhofer Institute for Cell Therapy and Immunology | Stolzing A.,Fraunhofer Institute for Cell Therapy and Immunology
BMC Cell Biology | Year: 2011

Background: Microglia, the macrophages of the brain, have been implicated in the causes of neurodegenerative diseases and display a loss of function during aging. Throughout life, microglia are replenished by limited proliferation of resident microglial cells. Replenishment by bone marrow-derived progenitor cells is still under debate. In this context, we investigated the differentiation of mouse microglia from bone marrow (BM) stem cells. Furthermore, we looked at the effects of FMS-like tyrosine kinase 3 ligand (Flt3L), astrocyte-conditioned medium (ACM) and GM-CSF on the differentiation to microglia-like cells.Methods: We assessed in vitro-derived microglia differentiation by marker expression (CD11b/CD45, F4/80), but also for the first time for functional performance (phagocytosis, oxidative burst) and in situ migration into living brain tissue. Integration, survival and migration were assessed in organotypic brain slices.Results: The cells differentiated from mouse BM show function, markers and morphology of primary microglia and migrate into living brain tissue. Flt3L displays a negative effect on differentiation while GM-CSF enhances differentiation.Conclusion: We conclude that in vitro-derived microglia are the phenotypic and functional equivalents to primary microglia and could be used in cell therapy. © 2011 Hinze and Stolzing; licensee BioMed Central Ltd.

Oelkrug C.,University of Nottingham | Oelkrug C.,Fraunhofer Institute for Cell Therapy and Immunology | Ramage J.M.,University of Nottingham
Clinical and Experimental Immunology | Year: 2014

Studies have documented that cancer patients with tumours which are highly infiltrated with cytotoxic T lymphocytes show enhanced survival rates. The ultimate goal of cancer immunotherapy is to elicit high-avidity tumourspecific T cells to migrate and kill malignant tumours. Novel antibody therapies such as ipilumimab (a cytotoxic T lymphocyte antigen-4 blocking antibody) show enhanced T cell infiltration into the tumour tissue and increased survival. More conventional therapies such as chemotherapy or anti-angiogenic therapy and recent therapies with oncolytic viruses have been shown to alter the tumour microenvironment and thereby lead to enhanced T cell infiltration. Understanding the mechanisms involved in the migration of high-avidity tumour-specific T cells into tumours will support and provide solutions for the optimization of therapeutic options in cancer immunotherapy. © 2014 The Authors. Clinical and Experimental Immunology published by John Wiley & Sons Ltd on behalf of British Society for Immunology.

Stolzing A.,Fraunhofer Institute for Cell Therapy and Immunology | Bauer E.,Fraunhofer Institute for Cell Therapy and Immunology | Scutt A.,University of Sheffield
Stem Cells and Development | Year: 2012

Both ageing and diabetes are associated with reduced numbers and functional viability of mesenchymal stem cells (MSCs) in vivo which in turn lead to degenerative pathologies of the musculoskeletal system. The overall aim of this study was to elucidate the effects of age and raised glucose levels on the proliferation and selfrenewal of rat nonadherent bone marrow MSCs (Na-BM-MSCs) in suspension cultures. MSC cultures isolated from 3- and 12-month-old rats were maintained using the "pour-off" method for up to 14 days in media containing different glucose levels and the phenotype, growth characteristics, colony forming unit-fibroblastic (CFU-f) numbers, and pluripotency characteristics of these cells were determined. This study indicates that rat adult bone marrow harbors pluripotent Na-BM-MSCs that seem to be unaffected by ageing during in vitro expansion. The Na-BM-MSCs express the pluripotency markers Oct4, Sox2, and Nanog. It was found that culture in high-glucose- containing medium had a negative effect on colony formation and differentiation. In contrast to classical MSC cultures, the generation of colonies by Na-BM-MSCs in suspension culture was not reduced in the older animals. The Na-BM-MSCs were found to express the pluripotency markers Oct4, Sox2, and Nanog, suggesting a more primitive stage of differentiation as compared with adherent MSCs. These data indicate that rat adult bone marrow harbors a population of pluripotent Na-BM-MSCs that appear to be relatively unaffected by ageing during in vitro expansion in suspension. © 2012 Mary Ann Liebert, Inc.

Ulbert S.,Fraunhofer Institute for Cell Therapy and Immunology
Intervirology | Year: 2011

West Nile virus (WNV) is a zoonotic virus that circulates in birds and is transmitted by mosquitoes. Incidentally, humans, horses and other mammals can also be infected. Disease symptoms caused by WNV range from fever to neurological complications, such as encephalitis or meningitis. Mortality is observed mostly in older and immunocompromised individuals. In recent years, epidemics caused by WNV in humans and horses have become more frequent in several Southern European countries, such as Italy and Greece. In 1999, WNV was introduced into the USA and spread over North America within a couple of years. The increasing number of WNV outbreaks is associated with the emergence of novel viral strains, which display higher virulence and greater epidemic potential for humans. Upon infection with WNV, the mammalian immune system counteracts the virus at several different levels. On the other side, WNV has developed elaborated escape mechanisms to avoid its elimination. This review summarizes recent findings in WNV research that help to understand the complex biology associated with this emerging pathogen. Copyright © 2011 S. Karger AG.

Ulbert S.,Fraunhofer Institute for Cell Therapy and Immunology | Magnusson S.E.,Novavax AB
Future Microbiology | Year: 2014

West Nile virus (WNV), an emerging mosquito-borne and zoonotic flavivirus, continues to spread worldwide and represents a major problem for human and veterinary medicine. In recent years, severe outbreaks were observed in the USA and Europe with neighboring countries, and the virus is considered to be endemic in an increasing number of areas. Although most infections remain asymptomatic, WNV can cause severe, even fatal, neurological disease, which affects mostly the elderly and immunocompromised individuals. Several vaccines have been licensed in the veterinary sector, but no human vaccine is available today. This review summarizes recent strategies that are being followed to develop WNV vaccines with emphasis on technologies suitable for the use in humans. © Sebastian Ulbert.

Rohani L.,Fraunhofer Institute for Cell Therapy and Immunology | Johnson A.A.,University of Arizona | Arnold A.,Fraunhofer Institute for Cell Therapy and Immunology | Stolzing A.,Fraunhofer Institute for Cell Therapy and Immunology
Aging Cell | Year: 2014

The discovery that somatic cells can be induced into a pluripotent state by the expression of reprogramming factors has enormous potential for therapeutics and human disease modeling. With regard to aging and rejuvenation, the reprogramming process resets an aged, somatic cell to a more youthful state, elongating telomeres, rearranging the mitochondrial network, reducing oxidative stress, restoring pluripotency, and making numerous other alterations. The extent to which induced pluripotent stem cell (iPSC)s mime embryonic stem cells is controversial, however, as iPSCs have been shown to harbor an epigenetic memory characteristic of their tissue of origin which may impact their differentiation potential. Furthermore, there are contentious data regarding the extent to which telomeres are elongated, telomerase activity is reconstituted, and mitochondria are reorganized in iPSCs. Although several groups have reported that reprogramming efficiency declines with age and is inhibited by genes upregulated with age, others have successfully generated iPSCs from senescent and centenarian cells. Mixed findings have also been published regarding whether somatic cells generated from iPSCs are subject to premature senescence. Defects such as these would hinder the clinical application of iPSCs, and as such, more comprehensive testing of iPSCs and their potential aging signature should be conducted. © 2013 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

An algae that survived more than 500 days in the International Space Station could be the answer to humanity's quest for a food that can be grown on planet Mars. In a nearly two-year experiment conducted on the ISS, Thomas Leya, from the Fraunhofer Institute for Cell Therapy and Immunology in Potsdam, Germany, and colleagues studied how the extreme conditions of space can affect algae. They found that a particular species of algae, which was placed on the exterior of the orbiting laboratory, survived the extreme temperature fluctuations, vacuum, as well as cosmic and UV radiation in space for a period of 16 months. The algae that survived belonged to the Sphaerocystis species, which is found in the Norwegian archipelago Svalbard. Another organism that survived the harsh condition outside the ISS is a cyanobacteria that belonged to the Nostoc species found in Antarctica. These species were selected for the study because they are known to be capable of withstanding extreme cold. The algae species protects itself by entering a dormant state wherein it forms thick walls and orange cysts that are rich in carotenoids, the chemical responsible for the carrot's orange color and is known to provide protection against radiation. "The experiment shows that some terrestrial organisms are robust enough to cope with months of exposure to open space conditions without a space suit," said Rene Demets, from the European Space Agency who was not involved in the study. The algae and bacteria are now added to the growing list of terrestrial organisms that can survive space. The list already includes other species of bacteria, lichen, and water bear. The study was part of the Biology and Mars Experiment (BIOMEX), which aims to understand the extent at which terrestrial life can survive in space. The experiment involved hundreds of specimens of lichens, fungi, bacteria, mosses, and algae that were exposed to extreme conditions which include temperatures ranging from -4 °F (-20 °C) and 116 °F (47 °C), near vacuum conditions and continuous blast of ultraviolet radiation. The organisms were transported into space on July 23, 2014 and endured 16 months on the outside of the ISS having only neutral-density filters to mitigate the effects of radiation. On June 2016, the BIOMEX lab was sent back to Earth, where researchers now conduct analysis of the DNA of what survived during the organisms' stay in outer space. Nearly all of the samples that returned from the orbiting laboratory developed into new populations. The green alga, in particular, developed orange-coloured resting stages. Researchers want to know whether the DNA of the ISS algae was damaged and to what extent. The findings could have significant applications such as in a mission to planet Mars someday. Producing food on the Red Planet is important for survival should humans colonize this extraterrestrial worlds in the future. Algae are known to produce proteins and oxygen, which makes them a good source of food. © 2017 Tech Times, All rights reserved. Do not reproduce without permission.

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