Biology Reference
In-Depth Information
The diminished function of the aged/diseased CP may respond much like other dis-
eases characterized by secretory cell dysfunction, where the principle of transplant-
ing or replacing a failing organ (such as CP) or specific cell type is a logical means of
restoring lost function. Based on the finding that CP secretes a multitude of growth
factors, we advanced the novel concept that the CP is a potential source of stable,
dose-controlled polypeptide delivery
[36]
.
In vitro
studies demonstrate that CP isolated and maintained in culture exerts potent
neuroprotective effects
[1-3]
. Conditioned media from alginate-encapsulated CP pro-
moted the survival and extension of neurites from embryonic cortical neurons against
serum deprivation-induced cell death. This effect was dose dependent and nearly
complete with 10-30% conditioned media. These data dovetail nicely with a study
in which mouse CP epithelial cells were cultured with dorsal root ganglion (DRG)
neurons
[2]
. After 4-5 hours of co-culture, the DRG neurons developed elongated
neuronal processes with elaborate branching patterns over the surface of the epithe-
lial cells. The ability of CP cells to provide a scaffold for the extension of neurites is
consistent with its known production of extracellular matrices including laminin and
fibronectin
[37,38]
. The trophic and tropic effects of CP establish potentially excellent
circumstances for the protection and repair of damaged CNS architecture.
In a similar fashion using
in vivo
models of brain disorders, the delivery of neu-
rotrophic factors via CP transplants to the site of injury also offers theoretical prom-
ise for treating spinal cord trauma. In a rat model of damaged spinal cord, syngeneic
fragments of CP grafted into the dorsal funiculus (C2 level) showed that epithelial
cells of the grafted CP survived well and induced robust regeneration of the damaged
axons of the spinal cord
[11]
. Injections of horseradish peroxidase into the sciatic
nerve labeled regenerating fibers extending from the fasciculus gracilis into the graft
within 7 days after transplant. This effect was evident for at least 10 months. Some
axons elongated rostrally into the dorsal funiculus and long-duration evoked poten-
tials were recorded 5 mm rostral to the lesion 8-10 months after grafting. This study
demonstrates that CP transplants afford robust therapeutic benefits in a model of spi-
nal cord injury.
4.8 Encapsulated Choroid Plexus Cells as
Immunoisolated Transplant Approach
In an effort to apply the concept of CP transplantation in the clinic, we recognized
the limitation of harvesting of CP from humans. The alternate approach of harvest-
ing CP from other species carries its own technical problems, especially the issue of
graft-versus-host diseases. In this regard, the idea of immunoisolation is appealing,
as it may circumvent the limitations inherent in cross-species (xenogeneic) transplan-
tation of CP. Immunoisolation is based on the observation that xenogeneic cells can
be protected from host rejection by encapsulating, or surrounding, them within an
immunoisolatory, semipermeable membrane. Single cells or small clusters of cells
can be enclosed within a selective, semipermeable membrane barrier that admits
