@article{RosenbaumSchickWollbornetal.2016, author = {Rosenbaum, Corinna and Schick, Martin Alexander and Wollborn, Jakob and Heider, Andreas and Scholz, Claus-J{\"u}rgen and Cecil, Alexander and Niesler, Beate and Hirrlinger, Johannes and Walles, Heike and Metzger, Marco}, title = {Activation of Myenteric Glia during Acute Inflammation In Vitro and In Vivo}, series = {PLoS One}, volume = {11}, journal = {PLoS One}, number = {3}, doi = {10.1371/journal.pone.0151335}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146544}, pages = {e0151335}, year = {2016}, abstract = {Background Enteric glial cells (EGCs) are the main constituent of the enteric nervous system and share similarities with astrocytes from the central nervous system including their reactivity to an inflammatory microenvironment. Previous studies on EGC pathophysiology have specifically focused on mucosal glia activation and its contribution to mucosal inflammatory processes observed in the gut of inflammatory bowel disease (IBD) patients. In contrast knowledge is scarce on intestinal inflammation not locally restricted to the mucosa but systemically affecting the intestine and its effect on the overall EGC network. Methods and Results In this study, we analyzed the biological effects of a systemic LPS-induced hyperinflammatory insult on overall EGCs in a rat model in vivo, mimicking the clinical situation of systemic inflammation response syndrome (SIRS). Tissues from small and large intestine were removed 4 hours after systemic LPS-injection and analyzed on transcript and protein level. Laser capture microdissection was performed to study plexus-specific gene expression alterations. Upon systemic LPS-injection in vivo we observed a rapid and dramatic activation of Glial Fibrillary Acidic Protein (GFAP)-expressing glia on mRNA level, locally restricted to the myenteric plexus. To study the specific role of the GFAP subpopulation, we established flow cytometry-purified primary glial cell cultures from GFAP promotor-driven EGFP reporter mice. After LPS stimulation, we analyzed cytokine secretion and global gene expression profiles, which were finally implemented in a bioinformatic comparative transcriptome analysis. Enriched GFAP+ glial cells cultured as gliospheres secreted increased levels of prominent inflammatory cytokines upon LPS stimulation. Additionally, a shift in myenteric glial gene expression profile was induced that predominantly affected genes associated with immune response. Conclusion and Significance Our findings identify the myenteric GFAP-expressing glial subpopulation as particularly susceptible and responsive to acute systemic inflammation of the gut wall and complement knowledge on glial involvement in mucosal inflammation of the intestine.}, language = {en} } @article{BurnsGoldsteinNewgreenetal.2016, author = {Burns, Alan J. and Goldstein, Allan M. and Newgreen, Donald F. and Stamp, Lincon and Sch{\"a}fer, Karl-Herbert and Metzger, Marco and Hotta, Ryo and Young, Heather M. and Andrews, Peter W. and Thapar, Nikhil and Belkind-Gerson, Jaime and Bondurand, Nadege and Bornstein, Joel C. and Chan, Wood Yee and Cheah, Kathryn and Gershon, Michael D. and Heuckeroth, Robert O. and Hofstra, Robert M.W. and Just, Lothar and Kapur, Raj P. and King, Sebastian K. and McCann, Conor J. and Nagy, Nandor and Ngan, Elly and Obermayr, Florian and Pachnis, Vassilis and Pasricha, Pankaj J. and Sham, Mai Har and Tam, Paul and Vanden Berghe, Pieter}, title = {White paper on guidelines concerning enteric nervous system stem cell therapy for enteric neuropathies}, series = {Developmental Biology}, volume = {417}, journal = {Developmental Biology}, number = {2}, doi = {10.1016/j.ydbio.2016.04.001}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-187415}, pages = {229-251}, year = {2016}, abstract = {Over the last 20 years, there has been increasing focus on the development of novel stem cell based therapies for the treatment of disorders and diseases affecting the enteric nervous system (ENS) of the gastrointestinal tract (so-called enteric neuropathies). Here, the idea is that ENS progenitor/stem cells could be transplanted into the gut wall to replace the damaged or absent neurons and glia of the ENS. This White Paper sets out experts' views on the commonly used methods and approaches to identify, isolate, purify, expand and optimize ENS stem cells, transplant them into the bowel, and assess transplant success, including restoration of gut function. We also highlight obstacles that must be overcome in order to progress from successful preclinical studies in animal models to ENS stem cell therapies in the clinic.}, language = {en} }