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Kurtz A.,Seoul National University | Kurtz A.,Berlin Brandenburg Center for Regenerative Therapies | Oh S.-J.,Seoul National University
Preventive Medicine | Year: 2012

Aging is characterized by reduced tissue and organ function, regenerative capacity, and accompanied by a decrease in tissue resident stem cell numbers and a loss of potency. The impact of aging on stem cell populations differs between tissues and depends on a number of non cell-intrinsic factors, including systemic changes associated with immune system alterations, as well as senescence related changes of the local cytoarchitecture. The latter has been studied in the context of environmental niche properties required for stem cell maintenance. Here, we will discuss the impact of the extracellular matrix (ECM) on stem cell maintenance, its changes during aging and its significance for stem cell therapy. We provide an overview on ECM components and examples of age associated remodeling of the cytoarchitecture. The interaction of stem cells with the ECM will be described and the importance of an intact and hospitable ECM for stem cell maintenance, differentiation and stem cell initiated tissue repair outlined. It is concluded that a remodeled ECM due to age related inflammation, fibrosis or oxidative stress provides an inadequate environment for endogenous regeneration or stem cell therapies. Means to provide adequate ECM for stem cell therapies and endogenous regeneration and the potential of antioxidants to prevent ECM damage and promote its repair and subsequently support regeneration are discussed. © 2012 Elsevier Inc..

Horn D.,Charite - Medical University of Berlin | Robinson P.N.,Charite - Medical University of Berlin | Robinson P.N.,Berlin Brandenburg Center for Regenerative Therapies
American Journal of Medical Genetics, Part A | Year: 2011

The association of progeroid features and lipodystrophy was very recently described in a female adult with additional manifestations of Marfan syndrome. Mutation analysis of the fibrillin I (FBN1) gene revealed a novel heterozygous frameshift mutation at the 3' end in that patient. Here, we report on a 3.5-year-old girl with progeroid facial signs of neonatal onset, lipodystrophy, large head circumference with corresponding hydrocephaly, and tall stature at the end of infancy. Her facial appearance showed convincing clinical similarities to the above-mentioned case. We identified a novel heterozygous de novo splice site mutation c.8226+1G>T affecting the last intron of FBN1. We suggest a specific clinical entity characterized by progeroid facial features, lipodystrophy, and at least some clinical signs of Marfan syndrome is associated with a subset of mutations located at the 3' end of FBN1. This phenotype which is different from that of classical Marfan syndrome could be caused by a truncated FBN1 protein which could escape nonsense-mediated RNA decay. © 2011 Wiley-Liss, Inc.

Zotzmann J.,Research Center Geesthacht GmbH | Zotzmann J.,Berlin Brandenburg Center for Regenerative Therapies | Behl M.,Research Center Geesthacht GmbH | Hofmann D.,Research Center Geesthacht GmbH | Lendlein A.,Research Center Geesthacht GmbH
Advanced Materials | Year: 2010

A reversible triple-shape effect is achieved for multi-phase polymer networks based on two different crystallizable segments. The reversibility of the two shape-changes is based on crystallization induced elongation (CIE) occurring during cooling and melting-Induced contraction (MIC) during heating under constant stress. (Figure Presented).

Schonig K.,Zentralinstitut For Seelische Gesundheit | Bujard H.,Zentrum fur Molekulare Biologie Heidelberg ZMBH | Gossen M.,Berlin Brandenburg Center for Regenerative Therapies | Gossen M.,Max Delbruck Center for Molecular Medicine
Methods in Enzymology | Year: 2010

Tetracycline-controlled transcriptional activation systems are widely used to control gene expression in transgenic animals in a truly conditional manner. By this we refer to the capability of these expression systems to control gene activities not only in a tissue specific and temporal defined but also reversible manner. This versatility has made the Tet regulatory systems to a preeminent tool in reverse mouse genetics. The development of the technology in the past 15 years will be reviewed and guidelines will be given for its implementation in creating transgenic rodents. Finally, we highlight some recent exciting applications of the Tet technology as well as its foreseeable combination with other emerging technologies in mouse transgenesis. © 2010 Elsevier Inc.

Behl M.,Helmholtz Center Geesthacht | Razzaq M.Y.,Helmholtz Center Geesthacht | Lendlein A.,Helmholtz Center Geesthacht | Lendlein A.,Berlin Brandenburg Center for Regenerative Therapies
Advanced Materials | Year: 2010

The thermally-induced shape-memory effect (SME) is the capability of a material to change its shape in a predefined way in response to heat In shapememory polymers (SMP) this shape change is the entropy-driven recovery of a mechanical deformation, which was obtained before by application of external stress and was temporarily fixed by formation of physical crosslinks. The high technological significance of SMP becomes apparent in many established products (e.g., packaging materials, assembling devices, textiles, and membranes) and the broad SMP development activities in the field of biomedical as well as aerospace applications (e.g., medical devices or morphing structures for aerospace vehicles). Inspired by the complex and diverse requirements of these applications fundamental research is aiming at multifunctional SMP, in which SME is combined with additional functions and is proceeding rapidly. In this review different concepts for the creation of multifunctional ity are derived from the various polymer network architectures of thermally-induced SMP. Multimaterial systems, such as nanocomposites, are described as well as one-component polymer systems, in which independent functions are integrated. Future challenges will be to transfer the concept of multifunctional ity to other emerging shape-memory technologies like lightsensitive SMP, reversible shape changing effects or triple-shape polymers. © 2010 WILEY-VCH Verlag GmbH S. Co. KGaA, Weinheim.

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