Generating Chimeric Spinal Cord
Generating Chimeric Spinal Cord
Object: To identify and evaluate stem cellderived oligodendrocytes obtained for cell transplantation therapies, the authors developed a novel model to examine single, adult oligodendrocytes in situ.
Methods: Green fluorescent proteinexpressing, mouse embryonic stem cells (ESCs) were neural induced and additionally staged in an oligosphere preparatory step for high-yield derivation of oligodendrocyte progenitors. These transplantable, induced progenitors were injected into postnatal Day 2 rat pups, in which spinal cord sections were then examined at 3 and 9 weeks posttransplantation.
Conclusions: Transplanted oligosphere ESCs survived and integrated anatomically into postnatal and adult white matter, generating targeted regions of chimeric spinal cord. A simple model for identifying adult oligodendrocytes in situ is presented, which is suitable for use in further studies examining functional myelination and derivation of oligodendrocytes from genetically engineered ESC lines, including human ESCs. Results from the model presented here demonstrate a unique method for examining transplantable oligodendrocyte progenitors derived from ESCs for repair of white matter disease.
If as little as 10 to 15% of white matter is spared after spinal cord injury, it may be enough to support mobility. Strategies to preserve injured white matter, prevent further loss to delayed degeneration, and reconstitute cellular loss through either endogenous regeneration or cellular transplantation targeted at this portion of the injured spinal cord may be enough for sufficient functional gain, sensory and/or motor. At this time, transplantation of young oligodendrocytes may prove to be a pragmatic approach to cellular reconstitution, especially after the demyelination has become chronic. Oligodendrocyte progenitors are at an early enough stage to multiply and yet at a late enough stage to remain restricted to their glial lineage in vivo. One important source of these cells is ESCs, which are expandable, maintaining stability under appropriate culture conditions, and genetically flexible. We have reported that after exposure to retinoic acid for 4 days, an additional culture scheme can be used to allow neural induced ESCs to enter an intermediate stage, known as oligospheres. This preparatory method can allow high-yield production of oligodendrocyte progenitors for in vitro or in vivo experiments.
Object: To identify and evaluate stem cellderived oligodendrocytes obtained for cell transplantation therapies, the authors developed a novel model to examine single, adult oligodendrocytes in situ.
Methods: Green fluorescent proteinexpressing, mouse embryonic stem cells (ESCs) were neural induced and additionally staged in an oligosphere preparatory step for high-yield derivation of oligodendrocyte progenitors. These transplantable, induced progenitors were injected into postnatal Day 2 rat pups, in which spinal cord sections were then examined at 3 and 9 weeks posttransplantation.
Conclusions: Transplanted oligosphere ESCs survived and integrated anatomically into postnatal and adult white matter, generating targeted regions of chimeric spinal cord. A simple model for identifying adult oligodendrocytes in situ is presented, which is suitable for use in further studies examining functional myelination and derivation of oligodendrocytes from genetically engineered ESC lines, including human ESCs. Results from the model presented here demonstrate a unique method for examining transplantable oligodendrocyte progenitors derived from ESCs for repair of white matter disease.
If as little as 10 to 15% of white matter is spared after spinal cord injury, it may be enough to support mobility. Strategies to preserve injured white matter, prevent further loss to delayed degeneration, and reconstitute cellular loss through either endogenous regeneration or cellular transplantation targeted at this portion of the injured spinal cord may be enough for sufficient functional gain, sensory and/or motor. At this time, transplantation of young oligodendrocytes may prove to be a pragmatic approach to cellular reconstitution, especially after the demyelination has become chronic. Oligodendrocyte progenitors are at an early enough stage to multiply and yet at a late enough stage to remain restricted to their glial lineage in vivo. One important source of these cells is ESCs, which are expandable, maintaining stability under appropriate culture conditions, and genetically flexible. We have reported that after exposure to retinoic acid for 4 days, an additional culture scheme can be used to allow neural induced ESCs to enter an intermediate stage, known as oligospheres. This preparatory method can allow high-yield production of oligodendrocyte progenitors for in vitro or in vivo experiments.
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