Limits...
Building bridges with astrocytes for spinal cord repair.

Miller RH - J. Biol. (2006)

Bottom Line: Simultaneous suppression of glial scarring and a general enhancement of axonal outgrowth has now been accomplished in an adult rat model of spinal cord transection.Transplantation of a novel astrocyte cell type derived from glial-restricted precursors in vitro raise the eventual possibility of cellular therapy for spinal cord injury.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neurosciences, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106-4975, USA. rhm3@case.edu

ABSTRACT
Simultaneous suppression of glial scarring and a general enhancement of axonal outgrowth has now been accomplished in an adult rat model of spinal cord transection. Transplantation of a novel astrocyte cell type derived from glial-restricted precursors in vitro raise the eventual possibility of cellular therapy for spinal cord injury.

Show MeSH

Related in: MedlinePlus

A model for the sequential generation of distinct cell types in the vertebrate CNS. Neural stem cells (NSCs) from the rat embryonic brain give rise to progenitors that are restricted to neuronal or glial fates. In vitro treatment of glial-derived precursors (GRPs) with members of the bone morphogenetic protein (BMP) family of secreted signaling molecules drives their differentiation into a distinct subtype of astrocyte (type 1 astrocyte, AstI) that promotes repair when transplanted to the injured adult spinal cord. In contrast, treatment of GRPs with the secreted protein Sonic hedgehog (Shh), a member of a different family of signaling molecules, causes their differentiation into type II astrocytes (AstII) and oligodendrocytes.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC1561530&req=5

Figure 1: A model for the sequential generation of distinct cell types in the vertebrate CNS. Neural stem cells (NSCs) from the rat embryonic brain give rise to progenitors that are restricted to neuronal or glial fates. In vitro treatment of glial-derived precursors (GRPs) with members of the bone morphogenetic protein (BMP) family of secreted signaling molecules drives their differentiation into a distinct subtype of astrocyte (type 1 astrocyte, AstI) that promotes repair when transplanted to the injured adult spinal cord. In contrast, treatment of GRPs with the secreted protein Sonic hedgehog (Shh), a member of a different family of signaling molecules, causes their differentiation into type II astrocytes (AstII) and oligodendrocytes.

Mentions: The cells utilized by Davies et al. [5] are termed GRP-derived astrocytes. This unusual name derives from the origins of the cells and reflects recent advances in our understanding of the cellular development of the CNS. Classical morphological studies identified the major epochs of neural development, in which neurons arise before glial cells [6]. Evidence that all major cell types might be derived from multipotent stem cells emerged from in vitro assays in which 'neurosphere'-producing cells were isolated, passaged and shown to generate neurons and the glial cell types astrocytes and oligodendrocytes [7]. These observations prompted an intensive search to define intermediate cell types between a multipotent stem cell and the fully differentiated cellular products. Using a series of in vitro approaches, Davies et al. [5] identified precursor cells derived from multipotent stem cells that appeared to be restricted to generating either neurons (neuron-restricted precursors, NRPs) or glial cells (glial-restricted precursors (GRPs) that give rise to astrocytes and oligodendrocytes) (Figure 1). Treatment of GRPs with a particular cocktail of growth factors and cytokines results in a population of cells, the GRP-derived astrocytes, that express canonical characteristics of astrocytes such as expression of the intermediate filament protein GFAP (glial fibrillary acidic protein). These were then used in the transplant studies. Remarkably, the GRP-derived astrocytes are far more effective at promoting axonal regeneration than are their less committed ancestor cells. Recent studies from other laboratories have used similar approaches to examine the ability of transplanted neural stem cells [8] or NRPs and GRPs [9] to promote spinal cord repair. Those analyses demonstrated the survival, migration and integration of the transplanted cells into the host tissue, but the characterization of axonal regrowth by Davies et al. [5] reveals that these precursor cell types have a very limited capacity to support axonal regeneration.


Building bridges with astrocytes for spinal cord repair.

Miller RH - J. Biol. (2006)

A model for the sequential generation of distinct cell types in the vertebrate CNS. Neural stem cells (NSCs) from the rat embryonic brain give rise to progenitors that are restricted to neuronal or glial fates. In vitro treatment of glial-derived precursors (GRPs) with members of the bone morphogenetic protein (BMP) family of secreted signaling molecules drives their differentiation into a distinct subtype of astrocyte (type 1 astrocyte, AstI) that promotes repair when transplanted to the injured adult spinal cord. In contrast, treatment of GRPs with the secreted protein Sonic hedgehog (Shh), a member of a different family of signaling molecules, causes their differentiation into type II astrocytes (AstII) and oligodendrocytes.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1561530&req=5

Figure 1: A model for the sequential generation of distinct cell types in the vertebrate CNS. Neural stem cells (NSCs) from the rat embryonic brain give rise to progenitors that are restricted to neuronal or glial fates. In vitro treatment of glial-derived precursors (GRPs) with members of the bone morphogenetic protein (BMP) family of secreted signaling molecules drives their differentiation into a distinct subtype of astrocyte (type 1 astrocyte, AstI) that promotes repair when transplanted to the injured adult spinal cord. In contrast, treatment of GRPs with the secreted protein Sonic hedgehog (Shh), a member of a different family of signaling molecules, causes their differentiation into type II astrocytes (AstII) and oligodendrocytes.
Mentions: The cells utilized by Davies et al. [5] are termed GRP-derived astrocytes. This unusual name derives from the origins of the cells and reflects recent advances in our understanding of the cellular development of the CNS. Classical morphological studies identified the major epochs of neural development, in which neurons arise before glial cells [6]. Evidence that all major cell types might be derived from multipotent stem cells emerged from in vitro assays in which 'neurosphere'-producing cells were isolated, passaged and shown to generate neurons and the glial cell types astrocytes and oligodendrocytes [7]. These observations prompted an intensive search to define intermediate cell types between a multipotent stem cell and the fully differentiated cellular products. Using a series of in vitro approaches, Davies et al. [5] identified precursor cells derived from multipotent stem cells that appeared to be restricted to generating either neurons (neuron-restricted precursors, NRPs) or glial cells (glial-restricted precursors (GRPs) that give rise to astrocytes and oligodendrocytes) (Figure 1). Treatment of GRPs with a particular cocktail of growth factors and cytokines results in a population of cells, the GRP-derived astrocytes, that express canonical characteristics of astrocytes such as expression of the intermediate filament protein GFAP (glial fibrillary acidic protein). These were then used in the transplant studies. Remarkably, the GRP-derived astrocytes are far more effective at promoting axonal regeneration than are their less committed ancestor cells. Recent studies from other laboratories have used similar approaches to examine the ability of transplanted neural stem cells [8] or NRPs and GRPs [9] to promote spinal cord repair. Those analyses demonstrated the survival, migration and integration of the transplanted cells into the host tissue, but the characterization of axonal regrowth by Davies et al. [5] reveals that these precursor cell types have a very limited capacity to support axonal regeneration.

Bottom Line: Simultaneous suppression of glial scarring and a general enhancement of axonal outgrowth has now been accomplished in an adult rat model of spinal cord transection.Transplantation of a novel astrocyte cell type derived from glial-restricted precursors in vitro raise the eventual possibility of cellular therapy for spinal cord injury.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neurosciences, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106-4975, USA. rhm3@case.edu

ABSTRACT
Simultaneous suppression of glial scarring and a general enhancement of axonal outgrowth has now been accomplished in an adult rat model of spinal cord transection. Transplantation of a novel astrocyte cell type derived from glial-restricted precursors in vitro raise the eventual possibility of cellular therapy for spinal cord injury.

Show MeSH
Related in: MedlinePlus