title: Perivascular Mesenchymal Stem Cells From the Adult Human Brain Harbor No Instrinsic Neuroectodermal but High Mesodermal Differentiation Potential.
abstract: Brain perivascular cells have recently been identified as a novel mesodermal cell type in the human brain. These cells reside in the perivascular niche and were shown to have mesodermal and, to a lesser extent, tissue-specific differentiation potential. Mesenchymal stem cells (MSCs) are widely proposed for use in cell therapy in many neurological disorders; therefore, it is of importance to better understand the "intrinsic" MSC population of the human brain. We systematically characterized adult human brain-derived pericytes during in vitro expansion and differentiation and compared these cells with fetal and adult human brain-derived neural stem cells (NSCs) and adult human bone marrow-derived MSCs. We found that adult human brain pericytes, which can be isolated from the hippocampus and from subcortical white matter, are-in contrast to adult human NSCs-easily expandable in monolayer cultures and show many similarities to human bone marrow-derived MSCs both regarding both surface marker expression and after whole transcriptome profile. Human brain pericytes showed a negligible propensity for neuroectodermal differentiation under various differentiation conditions but efficiently generated mesodermal progeny. Consequently, human brain pericytes resemble bone marrow-derived MSCs and might be very interesting for possible autologous and endogenous stem cell-based treatment strategies and cell therapeutic approaches for treating neurological diseases.
  
  
  CONCLUSIONS
  Perivascular mesenchymal stem cells (MSCs) recently gained significant interest because of their appearance in many tissues including the human brain. MSCs were often reported as being beneficial after transplantation in the central nervous system in different neurological diseases; therefore, adult brain perivascular cells derived from human neural tissue were systematically characterized concerning neural stem cell and MSC marker expression, transcriptomics, and mesodermal and inherent neuroectodermal differentiation potential in vitro and in vivo after in utero transplantation. This study showed the lack of an innate neuronal but high mesodermal differentiation potential. Because of their relationship to mesenchymal stem cells, these adult brain perivascular mesodermal cells are of great interest for possible autologous therapeutic use.
authors: Division of Neurodegenerative Diseases, Department of Neurology, University Center for Orthopaedics and Trauma Surgery and Center for Translational Bone, Joint and Soft Tissue Research, Department of Medicine I, Faculty of Medicine, and Department of Neurosurgery, Technische Universität Dresden, Dresden, Germany; Department of Biomedicine, University of Basel, Basel, Switzerland; Group of Computational Biology and Systems Biomedicine, Biodonostia Health Research Institute, San Sebastián, Spain; IKERBASQUE, Basque Foundation for Science, Bilbao, Spain; Department for Translational Neurodegeneration, Technical University of Munich, German Centre for Neurodegenerative Diseases, Munich, Germany; Geriatric Hospital Haag, Haag, Germany; Department of Neurology, Technical University of Munich, Munich, Germany; Center for Regenerative Therapies Dresden, Dresden, Germany; German Center for Neurodegenerative Diseases Dresden, Dresden, Germany.
authors: Xenia
authors: X
authors: Lojewski
authors: Division of Neurodegenerative Diseases, Department of Neurology, University Center for Orthopaedics and Trauma Surgery and Center for Translational Bone, Joint and Soft Tissue Research, Department of Medicine I, Faculty of Medicine, and Department of Neurosurgery, Technische Universität Dresden, Dresden, Germany; Department of Biomedicine, University of Basel, Basel, Switzerland; Group of Computational Biology and Systems Biomedicine, Biodonostia Health Research Institute, San Sebastián, Spain; IKERBASQUE, Basque Foundation for Science, Bilbao, Spain; Department for Translational Neurodegeneration, Technical University of Munich, German Centre for Neurodegenerative Diseases, Munich, Germany; Geriatric Hospital Haag, Haag, Germany; Department of Neurology, Technical University of Munich, Munich, Germany; Center for Regenerative Therapies Dresden, Dresden, Germany; German Center for Neurodegenerative Diseases Dresden, Dresden, Germany.
authors: Sumitra
authors: S
authors: Srimasorn
authors: Division of Neurodegenerative Diseases, Department of Neurology, University Center for Orthopaedics and Trauma Surgery and Center for Translational Bone, Joint and Soft Tissue Research, Department of Medicine I, Faculty of Medicine, and Department of Neurosurgery, Technische Universität Dresden, Dresden, Germany; Department of Biomedicine, University of Basel, Basel, Switzerland; Group of Computational Biology and Systems Biomedicine, Biodonostia Health Research Institute, San Sebastián, Spain; IKERBASQUE, Basque Foundation for Science, Bilbao, Spain; Department for Translational Neurodegeneration, Technical University of Munich, German Centre for Neurodegenerative Diseases, Munich, Germany; Geriatric Hospital Haag, Haag, Germany; Department of Neurology, Technical University of Munich, Munich, Germany; Center for Regenerative Therapies Dresden, Dresden, Germany; German Center for Neurodegenerative Diseases Dresden, Dresden, Germany.
authors: Juliane
authors: J
authors: Rauh
authors: Division of Neurodegenerative Diseases, Department of Neurology, University Center for Orthopaedics and Trauma Surgery and Center for Translational Bone, Joint and Soft Tissue Research, Department of Medicine I, Faculty of Medicine, and Department of Neurosurgery, Technische Universität Dresden, Dresden, Germany; Department of Biomedicine, University of Basel, Basel, Switzerland; Group of Computational Biology and Systems Biomedicine, Biodonostia Health Research Institute, San Sebastián, Spain; IKERBASQUE, Basque Foundation for Science, Bilbao, Spain; Department for Translational Neurodegeneration, Technical University of Munich, German Centre for Neurodegenerative Diseases, Munich, Germany; Geriatric Hospital Haag, Haag, Germany; Department of Neurology, Technical University of Munich, Munich, Germany; Center for Regenerative Therapies Dresden, Dresden, Germany; German Center for Neurodegenerative Diseases Dresden, Dresden, Germany.
authors: Silvan
authors: S
authors: Francke
authors: Division of Neurodegenerative Diseases, Department of Neurology, University Center for Orthopaedics and Trauma Surgery and Center for Translational Bone, Joint and Soft Tissue Research, Department of Medicine I, Faculty of Medicine, and Department of Neurosurgery, Technische Universität Dresden, Dresden, Germany; Department of Biomedicine, University of Basel, Basel, Switzerland; Group of Computational Biology and Systems Biomedicine, Biodonostia Health Research Institute, San Sebastián, Spain; IKERBASQUE, Basque Foundation for Science, Bilbao, Spain; Department for Translational Neurodegeneration, Technical University of Munich, German Centre for Neurodegenerative Diseases, Munich, Germany; Geriatric Hospital Haag, Haag, Germany; Department of Neurology, Technical University of Munich, Munich, Germany; Center for Regenerative Therapies Dresden, Dresden, Germany; German Center for Neurodegenerative Diseases Dresden, Dresden, Germany.
authors: Manja
authors: M
authors: Wobus
authors: Division of Neurodegenerative Diseases, Department of Neurology, University Center for Orthopaedics and Trauma Surgery and Center for Translational Bone, Joint and Soft Tissue Research, Department of Medicine I, Faculty of Medicine, and Department of Neurosurgery, Technische Universität Dresden, Dresden, Germany; Department of Biomedicine, University of Basel, Basel, Switzerland; Group of Computational Biology and Systems Biomedicine, Biodonostia Health Research Institute, San Sebastián, Spain; IKERBASQUE, Basque Foundation for Science, Bilbao, Spain; Department for Translational Neurodegeneration, Technical University of Munich, German Centre for Neurodegenerative Diseases, Munich, Germany; Geriatric Hospital Haag, Haag, Germany; Department of Neurology, Technical University of Munich, Munich, Germany; Center for Regenerative Therapies Dresden, Dresden, Germany; German Center for Neurodegenerative Diseases Dresden, Dresden, Germany.
authors: Verdon
authors: V
authors: Taylor
authors: Division of Neurodegenerative Diseases, Department of Neurology, University Center for Orthopaedics and Trauma Surgery and Center for Translational Bone, Joint and Soft Tissue Research, Department of Medicine I, Faculty of Medicine, and Department of Neurosurgery, Technische Universität Dresden, Dresden, Germany; Department of Biomedicine, University of Basel, Basel, Switzerland; Group of Computational Biology and Systems Biomedicine, Biodonostia Health Research Institute, San Sebastián, Spain; IKERBASQUE, Basque Foundation for Science, Bilbao, Spain; Department for Translational Neurodegeneration, Technical University of Munich, German Centre for Neurodegenerative Diseases, Munich, Germany; Geriatric Hospital Haag, Haag, Germany; Department of Neurology, Technical University of Munich, Munich, Germany; Center for Regenerative Therapies Dresden, Dresden, Germany; German Center for Neurodegenerative Diseases Dresden, Dresden, Germany.
authors: Marcos J
authors: MJ
authors: Araúzo-Bravo
authors: Division of Neurodegenerative Diseases, Department of Neurology, University Center for Orthopaedics and Trauma Surgery and Center for Translational Bone, Joint and Soft Tissue Research, Department of Medicine I, Faculty of Medicine, and Department of Neurosurgery, Technische Universität Dresden, Dresden, Germany; Department of Biomedicine, University of Basel, Basel, Switzerland; Group of Computational Biology and Systems Biomedicine, Biodonostia Health Research Institute, San Sebastián, Spain; IKERBASQUE, Basque Foundation for Science, Bilbao, Spain; Department for Translational Neurodegeneration, Technical University of Munich, German Centre for Neurodegenerative Diseases, Munich, Germany; Geriatric Hospital Haag, Haag, Germany; Department of Neurology, Technical University of Munich, Munich, Germany; Center for Regenerative Therapies Dresden, Dresden, Germany; German Center for Neurodegenerative Diseases Dresden, Dresden, Germany.
authors: Susanne
authors: S
authors: Hallmeyer-Elgner
authors: Division of Neurodegenerative Diseases, Department of Neurology, University Center for Orthopaedics and Trauma Surgery and Center for Translational Bone, Joint and Soft Tissue Research, Department of Medicine I, Faculty of Medicine, and Department of Neurosurgery, Technische Universität Dresden, Dresden, Germany; Department of Biomedicine, University of Basel, Basel, Switzerland; Group of Computational Biology and Systems Biomedicine, Biodonostia Health Research Institute, San Sebastián, Spain; IKERBASQUE, Basque Foundation for Science, Bilbao, Spain; Department for Translational Neurodegeneration, Technical University of Munich, German Centre for Neurodegenerative Diseases, Munich, Germany; Geriatric Hospital Haag, Haag, Germany; Department of Neurology, Technical University of Munich, Munich, Germany; Center for Regenerative Therapies Dresden, Dresden, Germany; German Center for Neurodegenerative Diseases Dresden, Dresden, Germany.
authors: Matthias
authors: M
authors: Kirsch
authors: Division of Neurodegenerative Diseases, Department of Neurology, University Center for Orthopaedics and Trauma Surgery and Center for Translational Bone, Joint and Soft Tissue Research, Department of Medicine I, Faculty of Medicine, and Department of Neurosurgery, Technische Universität Dresden, Dresden, Germany; Department of Biomedicine, University of Basel, Basel, Switzerland; Group of Computational Biology and Systems Biomedicine, Biodonostia Health Research Institute, San Sebastián, Spain; IKERBASQUE, Basque Foundation for Science, Bilbao, Spain; Department for Translational Neurodegeneration, Technical University of Munich, German Centre for Neurodegenerative Diseases, Munich, Germany; Geriatric Hospital Haag, Haag, Germany; Department of Neurology, Technical University of Munich, Munich, Germany; Center for Regenerative Therapies Dresden, Dresden, Germany; German Center for Neurodegenerative Diseases Dresden, Dresden, Germany.
authors: Sigrid
authors: S
authors: Schwarz
authors: Division of Neurodegenerative Diseases, Department of Neurology, University Center for Orthopaedics and Trauma Surgery and Center for Translational Bone, Joint and Soft Tissue Research, Department of Medicine I, Faculty of Medicine, and Department of Neurosurgery, Technische Universität Dresden, Dresden, Germany; Department of Biomedicine, University of Basel, Basel, Switzerland; Group of Computational Biology and Systems Biomedicine, Biodonostia Health Research Institute, San Sebastián, Spain; IKERBASQUE, Basque Foundation for Science, Bilbao, Spain; Department for Translational Neurodegeneration, Technical University of Munich, German Centre for Neurodegenerative Diseases, Munich, Germany; Geriatric Hospital Haag, Haag, Germany; Department of Neurology, Technical University of Munich, Munich, Germany; Center for Regenerative Therapies Dresden, Dresden, Germany; German Center for Neurodegenerative Diseases Dresden, Dresden, Germany.
authors: Johannes
authors: J
authors: Schwarz
authors: Division of Neurodegenerative Diseases, Department of Neurology, University Center for Orthopaedics and Trauma Surgery and Center for Translational Bone, Joint and Soft Tissue Research, Department of Medicine I, Faculty of Medicine, and Department of Neurosurgery, Technische Universität Dresden, Dresden, Germany; Department of Biomedicine, University of Basel, Basel, Switzerland; Group of Computational Biology and Systems Biomedicine, Biodonostia Health Research Institute, San Sebastián, Spain; IKERBASQUE, Basque Foundation for Science, Bilbao, Spain; Department for Translational Neurodegeneration, Technical University of Munich, German Centre for Neurodegenerative Diseases, Munich, Germany; Geriatric Hospital Haag, Haag, Germany; Department of Neurology, Technical University of Munich, Munich, Germany; Center for Regenerative Therapies Dresden, Dresden, Germany; German Center for Neurodegenerative Diseases Dresden, Dresden, Germany.
authors: Alexander
authors: A
authors: Storch
authors: Division of Neurodegenerative Diseases, Department of Neurology, University Center for Orthopaedics and Trauma Surgery and Center for Translational Bone, Joint and Soft Tissue Research, Department of Medicine I, Faculty of Medicine, and Department of Neurosurgery, Technische Universität Dresden, Dresden, Germany; Department of Biomedicine, University of Basel, Basel, Switzerland; Group of Computational Biology and Systems Biomedicine, Biodonostia Health Research Institute, San Sebastián, Spain; IKERBASQUE, Basque Foundation for Science, Bilbao, Spain; Department for Translational Neurodegeneration, Technical University of Munich, German Centre for Neurodegenerative Diseases, Munich, Germany; Geriatric Hospital Haag, Haag, Germany; Department of Neurology, Technical University of Munich, Munich, Germany; Center for Regenerative Therapies Dresden, Dresden, Germany; German Center for Neurodegenerative Diseases Dresden, Dresden, Germany andreas.hermann@uniklinikum-dresden.de.
authors: Andreas
authors: A
authors: Hermann
mesh_terms: D000328:Adult; D000818:Animals; D001921:Brain / Q000196:embryology; D002454:Cell Differentiation; D019070:Cell Lineage; D002648:Child; D005260:Female; D053686:Fetal Stem Cells / Q000166:cytology; D020869:Gene Expression Profiling; D006085:Graft Survival; D064593:Heterografts; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008648:Mesoderm; D051379:Mice; D008875:Middle Aged; D054258:Neural Plate; D009928:Organ Specificity; D020286:Pericytes / Q000166:cytology; D059467:Transcriptome; D066127:White Matter / Q000166:cytology; D055815:Young Adult
keywords: Brain pericytes; Brain perivascular cells; Hippocampus; Monolayer culture; Neural progenitor cells; White matter