Treatment of adult neural progenitor cells prior to transplantation affects graft survival and integration in a neonatal and adult rat model of selective retinal ganglion cell depletion.
OBJECTIVE
We tested whether microenvironmental changes surrounding apoptotic neural degeneration, cellular pre-treatment and timing of transplant can influence the survival and differentiation of transplanted cells. This was done by transplanting adult hippocampal precursor cells (AHPCs) into normal and retinal ganglion cell (RGC) depleted rat retinae.


METHODS
Apoptotic RGC death was induced in neonates by removal of the contralateral superior colliculus (SC) and in adults by unilateral optic nerve transection, with or without a peripheral nerve (PN) graft. AHPCs were transplanted 24 h after SC ablation, or 5, 7 or 14 days following optic nerve (ON) transection. Hosts received untreated grafts, or grafts treated by co-culture with embryonic retinal explants or the neuropeptide somatostatin.


RESULTS
AHPCs integrated within all neonatal and 65% of adult retinae. Greater numbers of AHPCs were observed within the ganglion cell layer (GCL) in SC lesioned hosts. Explant co-culture induced proliferation of grafted AHPCs within host retinae. Somatostatin-treatment resulted in reduced overall engraftment but increased integration within the GCL. In lesioned adults, greatest GCL engraftment was observed following 7 or 14 day grafts. Some AHPCs in the inner retina expressed neuronal antigens and extended processes into the ON.


CONCLUSIONS
These data indicate that various factors can influence the behaviour of grafted cells and work towards encouraging the functional restoration of retinal circuitry.
Mellough
Carla B
CB
School of Anatomy & Human Biology, The University of Western Australia, 35 Stirling Hwy, Crawley, Perth 6009, WA, Australia.
Cui
Qi
Q
Harvey
Alan R
AR
D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation; D002460:Cell Line; D018920:Coculture Techniques; D005123:Eye / Q000473:pathology; D006085:Graft Survival; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D011300:Preoperative Care; D051381:Rats; D011916:Rats, Inbred F344; D012160:Retina / Q000196:embryology; D012164:Retinal Diseases / Q000473:pathology / Q000601:surgery*; D012165:Retinal Ganglion Cells / Q000473:pathology*; D013004:Somatostatin / Q000494:pharmacology; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000187:drug effects / Q000473:pathology
D013004:Somatostatin