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Perivascular Mesenchymal Stem Cells From the Adult Human Brain Harbor No Instrinsic Neuroectodermal but High Mesodermal Differentiation Potential.
Stem Cells Transl Med 2015; 4(10):1223-33SC

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.

SIGNIFICANCE

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+Show Affiliations

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.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.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.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.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.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.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.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.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.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.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.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.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.

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26304036

Citation

Lojewski, Xenia, et al. "Perivascular Mesenchymal Stem Cells From the Adult Human Brain Harbor No Instrinsic Neuroectodermal but High Mesodermal Differentiation Potential." Stem Cells Translational Medicine, vol. 4, no. 10, 2015, pp. 1223-33.
Lojewski X, Srimasorn S, Rauh J, et al. Perivascular Mesenchymal Stem Cells From the Adult Human Brain Harbor No Instrinsic Neuroectodermal but High Mesodermal Differentiation Potential. Stem Cells Transl Med. 2015;4(10):1223-33.
Lojewski, X., Srimasorn, S., Rauh, J., Francke, S., Wobus, M., Taylor, V., ... Hermann, A. (2015). Perivascular Mesenchymal Stem Cells From the Adult Human Brain Harbor No Instrinsic Neuroectodermal but High Mesodermal Differentiation Potential. Stem Cells Translational Medicine, 4(10), pp. 1223-33. doi:10.5966/sctm.2015-0057.
Lojewski X, et al. Perivascular Mesenchymal Stem Cells From the Adult Human Brain Harbor No Instrinsic Neuroectodermal but High Mesodermal Differentiation Potential. Stem Cells Transl Med. 2015;4(10):1223-33. PubMed PMID: 26304036.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Perivascular Mesenchymal Stem Cells From the Adult Human Brain Harbor No Instrinsic Neuroectodermal but High Mesodermal Differentiation Potential. AU - Lojewski,Xenia, AU - Srimasorn,Sumitra, AU - Rauh,Juliane, AU - Francke,Silvan, AU - Wobus,Manja, AU - Taylor,Verdon, AU - Araúzo-Bravo,Marcos J, AU - Hallmeyer-Elgner,Susanne, AU - Kirsch,Matthias, AU - Schwarz,Sigrid, AU - Schwarz,Johannes, AU - Storch,Alexander, AU - Hermann,Andreas, Y1 - 2015/08/24/ PY - 2015/03/24/received PY - 2015/06/22/accepted PY - 2015/8/26/entrez PY - 2015/8/26/pubmed PY - 2015/12/19/medline KW - Brain pericytes KW - Brain perivascular cells KW - Hippocampus KW - Monolayer culture KW - Neural progenitor cells KW - White matter SP - 1223 EP - 33 JF - Stem cells translational medicine JO - Stem Cells Transl Med VL - 4 IS - 10 N2 - UNLABELLED: 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. SIGNIFICANCE: 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. SN - 2157-6564 UR - https://www.unboundmedicine.com/medline/citation/26304036/Perivascular_Mesenchymal_Stem_Cells_From_the_Adult_Human_Brain_Harbor_No_Instrinsic_Neuroectodermal_but_High_Mesodermal_Differentiation_Potential_ L2 - https://doi.org/10.5966/sctm.2015-0057 DB - PRIME DP - Unbound Medicine ER -