Effects of osteogenic protein-1 (OP-1) treatment on fetal spinal cord transplants to the anterior chamber of the eye.
Spinal cord injury represents a serious medical problem, and leads to chronic conditions that cannot be reversed at present. It has been suggested that trophic factor treatment may reduce the extent of damage and restore damaged neurons following the injury. We have tested the effects of osteogenic protein-1 (OP-1, also known as BMP-7), a member of the transforming growth factor-beta superfamily of growth factors, on developing spinal cord motor neurons in an intraocular transplantation model. Embryonic day 13 or 18 spinal cord tissue was dissected, incubated with OP-1 or vehicle, and injected into the anterior chamber of the eye of adult rats. Injections of additional doses of OP-1 were performed weekly, and the overall growth of the grafted tissue was assessed noninvasively. Four to 6 weeks postgrafting, animals were sacrificed and the tissue was processed for immunohistochemistry using antibodies directed against choline acetyltransferase, neurofilament, and the dendritic marker MAP-II. We found that OP-1 treatment stimulated overall growth of spinal cord tissue when dissected from embryonic day 18, but not from embryonic day 13. OP-1 treatment increased cell size and extent of cholinergic markers in motor neurons from both embryonic stages. The neurons also appeared to have a more extensive dendritic network in OP-1-treated grafts compared to controls. These findings indicate that OP-1 treatment may reduce the extent of axotomy-induced cell death of motor neurons, at least in the developing spinal cord.
Granholm
A C
AC
Department of Basic Science, University of Colorado Health Sciences Center, Denver 80262, USA. granholm@uchsc.edu
Sanders
L A
LA
Ickes
B
B
Albeck
D
D
Hoffer
B J
BJ
Young
D A
DA
Kaplan
P L
PL
D000818:Animals; D000867:Anterior Chamber / Q000601:surgery*; D000943:Antigens, Differentiation; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D016332:Fetal Tissue Transplantation; D005865:Gestational Age; D007091:Image Processing, Computer-Assisted; D009046:Motor Neurons / Q000166:cytology / Q000187:drug effects / Q000637:transplantation*; D051381:Rats; D011916:Rats, Inbred F344; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000196:embryology / Q000637:transplantation*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D000943:Antigens, Differentiation; C525821:Bmp7 protein, rat; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta