CYTOLOGICAL STUDIES OF DEVELOPING AND MATURE NEURONS

  • Wood, Patrick, (PI)
  • Bunge, Mary B, (PI)
  • Bethea, John R, (PI)
  • Bunge, Richard (PI)

Project: Research project

Description

The work proposed is a critical portion of one of the central goals of
The Miami Project to Cure Paralysis; to thoroughly explore the use of
Schwann cell (SC) transplantation in efforts to favorably influence the
response of neural tissue to injury and disease. We believe that the
remarkable capability of the SC to influence regenerative responses in
both peripheral and central neural tissue indicates potential for use in
human neural injury, particularly spinal cord injury. We outline a
series of complex tissue culture experiments aimed at gaining a fuller
understanding of the basic biology of the SC, especially of the human SC.
We believe a major effort to study the biology of the human SC is
required, for many of its basic characteristics appear to be different
from those that have been elucidated from the study of rodent tissue. We first propose to study the mechanisms by which rat SC function is
controlled by basal lamina (BL) assembly for we believe this aspect of
the regulation of SC function is critical to understanding its ability
to attain full functional capacity in central neural tissues. We will
use a myelinating tissue culture system to study the linkage between
expression of myelin-specific proteins and BL assembly, and will explore
the role of the cell adhesion molecule L1 in the signalling which
influences early SC development. We seek further to determine whether
SC surface integrins are involved in the regulation of SC function and
whether the cytoskeleton of the SC is involved in the signalling which
allows SC function to go forward as BL is assembled. Having arranged for a reliable source of viable human peripheral nerve,
we propose to use tissue culture methods to improve procedures for
separating SCs from human adult peripheral nerve, and to study the
cellular, soluble and matrix factors which regulate human SC
proliferation. Experiments are proposed to determine the capacity of the
human SC to produce extracellular matrix (ECM) components and to
determine whether ECM deposition regulates SC ensheathment and
myelination by the human SC, as it does in the rat. We will study the
ability of the human SC to provide trophic support for neural crest-
derived sensory neurons. In order not to limit our observations on human
SC function to tissue culture studies, we have developed a method of
introducing human SCs into guidance channels placed to bridge gaps in the
immune-deficient rodent peripheral nerve, and will use this system to
study the regulation of human SC proliferation in vivo, as well as the
ability of human SCs to promote peripheral axonal regeneration. Finally, we propose to introduce a recombinant retrovirus which contains
sequences for both beta-galactosidase and basic fibroblast growth factor
and to subsequently compare the ability of the infected cells to support
neuronal health and induce neurite growth, as well as to determine how
this genetic change alters the ability of the SC in undertaking its basic
function of axonal ensheathment, BL assembly, and myelination. These basic studies of SC biology are considered essential to any
consideration of use of this cell in autotransplantation in human
patients with neural injury. The potential of this cell to influence
axonal regeneration as well as to repair demyelination gives this work
considerable urgency.
StatusFinished
Effective start/end date5/1/764/30/17

Funding

  • National Institutes of Health
  • National Institutes of Health: $415,300.00
  • National Institutes of Health: $296,592.00
  • National Institutes of Health: $292,832.00
  • National Institutes of Health: $419,495.00
  • National Institutes of Health: $310,667.00
  • National Institutes of Health: $301,617.00
  • National Institutes of Health: $334,267.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $25,000.00
  • National Institutes of Health: $419,495.00
  • National Institutes of Health: $404,814.00
  • National Institutes of Health: $409,015.00
  • National Institutes of Health
  • National Institutes of Health: $285,341.00
  • National Institutes of Health: $330,924.00
  • National Institutes of Health: $277,032.00
  • National Institutes of Health: $334,267.00
  • National Institutes of Health: $300,595.00

Fingerprint

Neurons
Schwann Cells
Axons
Adenine Nucleotides
Neuregulin-1
Growth
Colforsin
Brain Stem
Mitogens
Neuregulins
Regeneration
Autologous Transplantation
Cell Proliferation
Telomere Shortening
Extracellular Matrix
Cell Aging
Myelin Sheath
Telomerase
Rodentia
Spinal Cord Injuries

ASJC

  • Medicine(all)
  • Neuroscience(all)