title: Concise Review: Increasing the Validity of Cerebrovascular Disease Models and Experimental Methods for Translational Stem Cell Research.
abstract: Interspecies differences, anatomical and physiological aspects, as wells as simplified study designs contribute to an overestimation of treatment effects and limit the transferability of experimental results into clinical applications. Confounders of cell therapies for cerebrovascular disorders (CVD) include common CVD comorbidities, frequent medications potentially affecting endogenous and transplanted stem cells, as well as age- and immune-system-related effects. All those can contribute to a substantial modeling bias, ultimately limiting the prospective quality of preclinical research programs regarding the clinical value of a particular cell therapy. In this review, we discuss the nature and impact of most relevant confounders. We provide suggestions on how they can be considered to enhance the validity of CVD models in stem cell research. Acknowledging substantial and sometimes surprising effects of housing conditions, chronobiology, and intersex differences will further augment the translational value of animal models. We finally discuss options for the implementation of high-quality functional and imaging readout protocols. Altogether, this might help to gain a more holistic picture about the therapeutic impact of a particular cell therapy for CVD, but also on potential side and off-site effects of the intervention. Stem Cells 2017;35:1141-1153.
authors.affiliation: Department of Translational Medicine and Cell Technology, Fraunhofer Research Institution for Marine Biotechnology and Cell Technology, Lübeck, Germany.|Institute for Medical and Marine Biotechnology, University of Lübeck, Lübeck, Germany.
authors.forename: Johannes
authors.identifier: 0000-0003-3956-4164
authors.initials: J
authors.lastname: Boltze
authors.affiliation: Department of Cell Therapy, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany.|Department of Radiology, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pennsylvania, USA.
authors.forename: Franziska
authors.initials: F
authors.lastname: Nitzsche
authors.affiliation: Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
authors.forename: Jukka
authors.initials: J
authors.lastname: Jolkkonen
authors.affiliation: Department of Cell Therapy, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany.|Department of Neurology, University of Leipzig, Germany.
authors.forename: Gesa
authors.initials: G
authors.lastname: Weise
authors.affiliation: Department of Cell Therapy, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Pösel
authors.affiliation: Department of Cell Therapy, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany.|Department of Nuclear Medicine, University Hospital Leipzig, Germany.
authors.forename: Björn
authors.initials: B
authors.lastname: Nitzsche
authors.affiliation: Department of Cell Therapy, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany.|Institute of Pathology, University Medical Center Mainz, Germany.
authors.forename: Daniel-Christoph
authors.initials: DC
authors.lastname: Wagner
mesh_terms: D000375:Aging / Q000473:pathology; D000818:Animals; D002561:Cerebrovascular Disorders / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D004195:Disease Models, Animal; D006801:Humans; D007107:Immune System / Q000473:pathology; D057905:Stem Cell Research; D057170:Translational Research, Biomedical
keywords: Animal models; Cerebrovascular diseases; Reliability; Stem cell transplantation; Stem cells; Stroke; Validity; Vascular dementia