In vitro generation of three-dimensional substrate-adherent embryonic stem cell-derived neural aggregates for application in animal models of neurological disorders.

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In vitro generation of three-dimensional substrate-adherent embryonic stem cell-derived neural aggregates for application in animal models of neurological disorders. / Hargus, Gunnar; Cui, Yifang; Dihné, Marcel; Bernreuther, Christian; Schachner, Melitta.

in: Curr Protoc Stem Cell Biol, Jahrgang Chapter 2, 2012, S. 11.

Publikationen: SCORING: Beitrag in Fachzeitschrift/ZeitungSCORING: ZeitschriftenaufsatzForschungBegutachtung

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@article{8e2160315758439d8801d24e79ba362b,
title = "In vitro generation of three-dimensional substrate-adherent embryonic stem cell-derived neural aggregates for application in animal models of neurological disorders.",
abstract = "In vitro-differentiated embryonic stem (ES) cells comprise a useful source for cell replacement therapy, but the efficiency and safety of a translational approach are highly dependent on optimized protocols for directed differentiation of ES cells into the desired cell types in vitro. Furthermore, the transplantation of three-dimensional ES cell-derived structures instead of a single-cell suspension may improve graft survival and function by providing a beneficial microenvironment for implanted cells. To this end, we have developed a new method to efficiently differentiate mouse ES cells into neural aggregates that consist predominantly (>90%) of postmitotic neurons, neural progenitor cells, and radial glia-like cells. When transplanted into the excitotoxically lesioned striatum of adult mice, these substrate-adherent embryonic stem cell-derived neural aggregates (SENAs) showed significant advantages over transplanted single-cell suspensions of ES cell-derived neural cells, including improved survival of GABAergic neurons, increased cell migration, and significantly decreased risk of teratoma formation. Furthermore, SENAs mediated functional improvement after transplantation into animal models of Parkinson's disease and spinal cord injury. This unit describes in detail how SENAs are efficiently derived from mouse ES cells in vitro and how SENAs are isolated for transplantation. Furthermore, methods are presented for successful implantation of SENAs into animal models of Huntington's disease, Parkinson's disease, and spinal cord injury to study the effects of stem cell-derived neural aggregates in a disease context in vivo.",
keywords = "Animals, Female, Disease Models, Animal, Mice, Mice, Inbred C57BL, Cell Differentiation, Cell Separation, Cell Adhesion, Cell Culture Techniques/*methods, *Stem Cell Transplantation, Cell Aggregation, Embryoid Bodies/cytology, Embryonic Stem Cells/*cytology/*transplantation, Huntington Disease/therapy, Nervous System Diseases/*therapy, Neurons/*cytology/*transplantation, Parkinson Disease/therapy, Spinal Cord Injuries/therapy, Animals, Female, Disease Models, Animal, Mice, Mice, Inbred C57BL, Cell Differentiation, Cell Separation, Cell Adhesion, Cell Culture Techniques/*methods, *Stem Cell Transplantation, Cell Aggregation, Embryoid Bodies/cytology, Embryonic Stem Cells/*cytology/*transplantation, Huntington Disease/therapy, Nervous System Diseases/*therapy, Neurons/*cytology/*transplantation, Parkinson Disease/therapy, Spinal Cord Injuries/therapy",
author = "Gunnar Hargus and Yifang Cui and Marcel Dihn{\'e} and Christian Bernreuther and Melitta Schachner",
year = "2012",
language = "English",
volume = "Chapter 2",
pages = "11",
journal = "Current protocols in stem cell biology",
issn = "1938-8969",
publisher = "John Wiley and Sons Inc.",

}

RIS

TY - JOUR

T1 - In vitro generation of three-dimensional substrate-adherent embryonic stem cell-derived neural aggregates for application in animal models of neurological disorders.

AU - Hargus, Gunnar

AU - Cui, Yifang

AU - Dihné, Marcel

AU - Bernreuther, Christian

AU - Schachner, Melitta

PY - 2012

Y1 - 2012

N2 - In vitro-differentiated embryonic stem (ES) cells comprise a useful source for cell replacement therapy, but the efficiency and safety of a translational approach are highly dependent on optimized protocols for directed differentiation of ES cells into the desired cell types in vitro. Furthermore, the transplantation of three-dimensional ES cell-derived structures instead of a single-cell suspension may improve graft survival and function by providing a beneficial microenvironment for implanted cells. To this end, we have developed a new method to efficiently differentiate mouse ES cells into neural aggregates that consist predominantly (>90%) of postmitotic neurons, neural progenitor cells, and radial glia-like cells. When transplanted into the excitotoxically lesioned striatum of adult mice, these substrate-adherent embryonic stem cell-derived neural aggregates (SENAs) showed significant advantages over transplanted single-cell suspensions of ES cell-derived neural cells, including improved survival of GABAergic neurons, increased cell migration, and significantly decreased risk of teratoma formation. Furthermore, SENAs mediated functional improvement after transplantation into animal models of Parkinson's disease and spinal cord injury. This unit describes in detail how SENAs are efficiently derived from mouse ES cells in vitro and how SENAs are isolated for transplantation. Furthermore, methods are presented for successful implantation of SENAs into animal models of Huntington's disease, Parkinson's disease, and spinal cord injury to study the effects of stem cell-derived neural aggregates in a disease context in vivo.

AB - In vitro-differentiated embryonic stem (ES) cells comprise a useful source for cell replacement therapy, but the efficiency and safety of a translational approach are highly dependent on optimized protocols for directed differentiation of ES cells into the desired cell types in vitro. Furthermore, the transplantation of three-dimensional ES cell-derived structures instead of a single-cell suspension may improve graft survival and function by providing a beneficial microenvironment for implanted cells. To this end, we have developed a new method to efficiently differentiate mouse ES cells into neural aggregates that consist predominantly (>90%) of postmitotic neurons, neural progenitor cells, and radial glia-like cells. When transplanted into the excitotoxically lesioned striatum of adult mice, these substrate-adherent embryonic stem cell-derived neural aggregates (SENAs) showed significant advantages over transplanted single-cell suspensions of ES cell-derived neural cells, including improved survival of GABAergic neurons, increased cell migration, and significantly decreased risk of teratoma formation. Furthermore, SENAs mediated functional improvement after transplantation into animal models of Parkinson's disease and spinal cord injury. This unit describes in detail how SENAs are efficiently derived from mouse ES cells in vitro and how SENAs are isolated for transplantation. Furthermore, methods are presented for successful implantation of SENAs into animal models of Huntington's disease, Parkinson's disease, and spinal cord injury to study the effects of stem cell-derived neural aggregates in a disease context in vivo.

KW - Animals

KW - Female

KW - Disease Models, Animal

KW - Mice

KW - Mice, Inbred C57BL

KW - Cell Differentiation

KW - Cell Separation

KW - Cell Adhesion

KW - Cell Culture Techniques/methods

KW - Stem Cell Transplantation

KW - Cell Aggregation

KW - Embryoid Bodies/cytology

KW - Embryonic Stem Cells/cytology/transplantation

KW - Huntington Disease/therapy

KW - Nervous System Diseases/therapy

KW - Neurons/cytology/transplantation

KW - Parkinson Disease/therapy

KW - Spinal Cord Injuries/therapy

KW - Animals

KW - Female

KW - Disease Models, Animal

KW - Mice

KW - Mice, Inbred C57BL

KW - Cell Differentiation

KW - Cell Separation

KW - Cell Adhesion

KW - Cell Culture Techniques/methods

KW - Stem Cell Transplantation

KW - Cell Aggregation

KW - Embryoid Bodies/cytology

KW - Embryonic Stem Cells/cytology/transplantation

KW - Huntington Disease/therapy

KW - Nervous System Diseases/therapy

KW - Neurons/cytology/transplantation

KW - Parkinson Disease/therapy

KW - Spinal Cord Injuries/therapy

M3 - SCORING: Journal article

VL - Chapter 2

SP - 11

JO - Current protocols in stem cell biology

JF - Current protocols in stem cell biology

SN - 1938-8969

ER -