Glial restricted precursor cell transplant with cyclic adenosine monophosphate improved some autonomic functions but resulted in a reduced graft size after spinal cord contusion injury in rats.
Transplantation of glial restricted precursor (GRP) cells has been shown to reduce glial scarring after spinal cord injury (SCI) and, in combination with neuronal restricted precursor (NRP) cells or enhanced expression of neurotrophins, to improve recovery of function after SCI. We hypothesized that combining GRP transplants with rolipram and cAMP would improve functional recovery, similar to that seen after combining Schwann cell transplants with increasing cAMP. A short term study, (1) uninjured control, (2) SCI+vehicle, and (3) SCI+cAMP, showed that spinal cord [cAMP] was increased 14days after SCI. We used 51 male rats subjected to a thoracic SCI for a 12-week survival study: (1) SCI+vehicle, (2) SCI+GRP, (3) SCI+cAMP, (4) SCI+GRP+cAMP, and (5) uninjured endpoint age-matched control (AM). Rolipram was administered for 2weeks after SCI. At 9days after SCI, GRP transplantation and injection of dibutyryl-cAMP into the spinal cord were performed. GRP cells survived, differentiated, and formed extensive transplants that were well integrated with host tissue. Presence of GRP cells increased the amount of tissue in the lesion; however, cAMP reduced the graft size. White matter sparing at the lesion epicenter was not affected. Serotonergic input to the lumbosacral spinal cord was not affected by treatment, but the amount of serotonin immediately caudal to the lesion was reduced in the cAMP groups. Using telemetric monitoring of corpus spongiosum penis pressure we show that the cAMP groups regained the same number of micturitions per 24hours when compared to the AM group, however, the frequency of peak pressures was increased in these groups compared to the AM group. In contrast, the GRP groups had similar frequency of peak pressures compared to baseline and the AM group. Animals that received GRP cells regained the same number of erectile events per 24hours compared to baseline and the AM group. Since cAMP reduced the GRP transplant graft, and some modest positive effects were seen that could be attributable to both GRP or cAMP, future research is required to determine how cAMP affects survival, proliferation, and/or function of progenitor cells and how this is related to function. cAMP may not always be a desirable addition to a progenitor cell transplantation strategy after SCI.
Brain and Spinal Injury Center, Department of Neurological Surgery, 1001 Potrero Ave. Bld 1 Rm 101, University of California, San Francisco, CA 94110, USA. Yvette.nout@ucsf.edu
Yvette S
YS
Nout
Esther
E
Culp
Markus H
MH
Schmidt
C Amy
CA
Tovar
Christoph
C
Pröschel
Margot
M
Mayer-Pröschel
Mark D
MD
Noble
Michael S
MS
Beattie
Jacqueline C
JC
Bresnahan
D000704:Analysis of Variance; D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D002454:Cell Differentiation; D000242:Cyclic AMP / Q000378:metabolism / Q000627:therapeutic use*; D004195:Disease Models, Animal; D007211:Indoles; D008124:Locomotion / Q000187:drug effects; D008297:Male; D009046:Motor Neurons / Q000187:drug effects / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects / Q000637:transplantation*; D010410:Penile Erection / Q000187:drug effects; D051381:Rats; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D012018:Reflex / Q000187:drug effects; D013119:Spinal Cord Injuries / Q000503:physiopathology* / Q000601:surgery*; D033581:Stem Cell Transplantation / Q000379:methods*
D007211:Indoles; D009419:Nerve Tissue Proteins; C007293:DAPI; D000242:Cyclic AMP