zur Nieden N.I.,Fraunhofer Institute for Cell Therapy and Immunology
Methods in molecular biology (Clifton, N.J.) | Year: 2011
Current orthopedic practice to treat osteo-degenerative diseases, such as osteoporosis, calls for antiresorptive therapies and anabolic bone medications. In some cases, surgery, in which metal rods are inserted into the bones, brings symptomatic relief. As these treatments may ameliorate the symptoms, but cannot cure the underlying dysregulation of the bone, the orthopedic field seems ripe for regenerative therapies using transplantation of stem cells. Stem cells bring with them the promise of completely curing a disease state, as these are the cells that normally regenerate tissues in a healthy organism. This chapter assembles reports that have successfully used stem cells to generate osteoblasts, osteoclasts, and chondrocytes - the cells that can be found in healthy bone tissue - in culture, and review and collate studies about animal models that were employed to test the function of these in vitro "made" cells. A particular emphasis is placed on embryonic stem cells, the most versatile of all stem cells. Due to their pluripotency, embryonic stem cells represent the probably most challenging stem cells to bring into the clinic, and therefore, the associated problems are discussed to put into perspective where the field currently is and what we can expect for the future.
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.
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.
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.
Muller M.,University of Munster |
Muller M.,Fraunhofer Institute for Cell Therapy and Immunology |
Lutter D.,University of Munster |
Puschel A.W.,University of Munster
Journal of Cell Science | Year: 2010
Wee1 is well characterized as a cell-cycle checkpoint kinase that regulates the entry into mitosis in dividing cells. Here we identify a novel function of Wee1 in postmitotic neurons during the establishment of distinct axonal and dendritic compartments, which is an essential step during neuronal development. Wee1 is expressed in unpolarized neurons but is downregulated after neurons have extended an axon. Suppression of Wee1 impairs the formation of minor neurites but does not interfere with axon formation. However, neuronal polarity is disrupted when neurons fail to downregulate Wee1. The kinases SadA and SadB (Sad kinases) phosphorylate Wee1 and are required to initiate its downregulation in polarized neurons. Wee1 expression persists in neurons that are deficient in SadA and SadB and disrupts neuronal polarity. Knockdown of Wee1 rescues the Sada -/-;Sadb -/- mutant phenotype and restores normal polarity in these neurons. Our results demonstrate that the regulation of Wee1 by SadA and SadB kinases is essential for the differentiation of polarized neurons.