Embryonic stem cell-derived L1 overexpressing neural aggregates enhance recovery after spinal cord injury in mice.
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Embryonic stem cell-derived L1 overexpressing neural aggregates enhance recovery after spinal cord injury in mice. / Cui, Yifang; Xu, Jinchong; Hargus, Gunnar; Jakovcevski, Igor; Schachner, Melitta; Bernreuther, Christian.
in: PLOS ONE, Jahrgang 6, Nr. 3, 3, 2011, S. 17126.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Embryonic stem cell-derived L1 overexpressing neural aggregates enhance recovery after spinal cord injury in mice.
AU - Cui, Yifang
AU - Xu, Jinchong
AU - Hargus, Gunnar
AU - Jakovcevski, Igor
AU - Schachner, Melitta
AU - Bernreuther, Christian
PY - 2011
Y1 - 2011
N2 - An obstacle to early stem cell transplantation into the acutely injured spinal cord is poor survival of transplanted cells. Transplantation of embryonic stem cells as substrate adherent embryonic stem cell-derived neural aggregates (SENAs) consisting mainly of neurons and radial glial cells has been shown to enhance survival of grafted cells in the injured mouse brain. In the attempt to promote the beneficial function of these SENAs, murine embryonic stem cells constitutively overexpressing the neural cell adhesion molecule L1 which favors axonal growth and survival of grafted and imperiled cells in the inhibitory environment of the adult mammalian central nervous system were differentiated into SENAs and transplanted into the spinal cord three days after compression lesion. Mice transplanted with L1 overexpressing SENAs showed improved locomotor function when compared to mice injected with wild-type SENAs. L1 overexpressing SENAs showed an increased number of surviving cells, enhanced neuronal differentiation and reduced glial differentiation after transplantation when compared to SENAs not engineered to overexpress L1. Furthermore, L1 overexpressing SENAs rescued imperiled host motoneurons and parvalbumin-positive interneurons and increased numbers of catecholaminergic nerve fibers distal to the lesion. In addition to encouraging the use of embryonic stem cells for early therapy after spinal cord injury L1 overexpression in the microenvironment of the lesioned spinal cord is a novel finding in its functions that would make it more attractive for pre-clinical studies in spinal cord regeneration and most likely other diseases of the nervous system.
AB - An obstacle to early stem cell transplantation into the acutely injured spinal cord is poor survival of transplanted cells. Transplantation of embryonic stem cells as substrate adherent embryonic stem cell-derived neural aggregates (SENAs) consisting mainly of neurons and radial glial cells has been shown to enhance survival of grafted cells in the injured mouse brain. In the attempt to promote the beneficial function of these SENAs, murine embryonic stem cells constitutively overexpressing the neural cell adhesion molecule L1 which favors axonal growth and survival of grafted and imperiled cells in the inhibitory environment of the adult mammalian central nervous system were differentiated into SENAs and transplanted into the spinal cord three days after compression lesion. Mice transplanted with L1 overexpressing SENAs showed improved locomotor function when compared to mice injected with wild-type SENAs. L1 overexpressing SENAs showed an increased number of surviving cells, enhanced neuronal differentiation and reduced glial differentiation after transplantation when compared to SENAs not engineered to overexpress L1. Furthermore, L1 overexpressing SENAs rescued imperiled host motoneurons and parvalbumin-positive interneurons and increased numbers of catecholaminergic nerve fibers distal to the lesion. In addition to encouraging the use of embryonic stem cells for early therapy after spinal cord injury L1 overexpression in the microenvironment of the lesioned spinal cord is a novel finding in its functions that would make it more attractive for pre-clinical studies in spinal cord regeneration and most likely other diseases of the nervous system.
KW - Animals
KW - Mice
KW - Stem Cell Transplantation
KW - Cell Differentiation
KW - Neural Cell Adhesion Molecule L1/metabolism
KW - Astrocytes/cytology
KW - Embryonic Stem Cells/metabolism
KW - Interneurons/cytology
KW - Neuroglia/cytology
KW - Spinal Cord Injuries/metabolism/rehabilitation
KW - Animals
KW - Mice
KW - Stem Cell Transplantation
KW - Cell Differentiation
KW - Neural Cell Adhesion Molecule L1/metabolism
KW - Astrocytes/cytology
KW - Embryonic Stem Cells/metabolism
KW - Interneurons/cytology
KW - Neuroglia/cytology
KW - Spinal Cord Injuries/metabolism/rehabilitation
U2 - 10.1371/journal.pone.0017126
DO - 10.1371/journal.pone.0017126
M3 - SCORING: Journal article
VL - 6
SP - 17126
JO - PLOS ONE
JF - PLOS ONE
SN - 1932-6203
IS - 3
M1 - 3
ER -
