Trasplante de glía envolvente olfatoria para reparar lesiones crónicas de la médula espinal de ratas adultas: de roedores a primates.
Olfactory bulb Ensheathing Glia (OB-OEG) promote functional recovery and histological repair when transplanted immediately after spinal cord injury. We have checked in rats, if OB-OEG transplantation is also efficient when transplanted at subacute and chronic injury stages after complete spinal cord transection. OB-OEG were grafted at either one (subacute) or four (chronic) months post-lesion. During seven months following transplantation, rats from both OEG-transplanted groups presented a significant progressive improvement of motor function in the climbing test, not observed in non-grafted animals. OB-OEG grafts were equally efficient at subacute or chronic stages. Quantitative analysis by peroxidase tracing revealed that, in transplanted animals, axons of brainstem spinal cord-projecting neurons grew beyond the caudal stump border. Axons from neurons located in red nucleus, reticular formation, locus coeruleus, vestibular and raphe nuclei crossed the scar and regenerated distally in the spinal cord. The number of regenerating neurons was significantly higher in every transplanted group (subacute and chronic) than in the non-transplanted one, but transplanted groups did not differ one another. A positive linear correlation was found between the functional recovery of the animals and the number of brainstem regenerating neurons. OB-OEG transplantation can be delayed up to four months. This provides enough time to obtain and grow OEG for autologous use and also for patient stabilization before transplantation.
To provide insight into the feasibility of OB-OEG use in human therapy, we studied in other close primates the suitability of these cells for this purpose. We demonstrated that OEG can be obtained from olfactory bulbs of adult macaca monkeys. However, unlike from rodent, primate OB-OEG are non-senescent, exhibit longer lifespan, are less sensitive to culture shock, and preserve for 2.5 months in vitro a phenotype suitable for grafting. One single macaca olfactory bulb gives in short-term enough OEG to guarantee autologous transplantation at the acute stage, and moreover, after long-term cultures may yield 20 thousand million OEG for storage in banks of cells for further use. Therefore, adult olfactory bulbs from macacas constitute a reliable source of OEG for cell therapy, and autologous transplantation of these cells is a viable approach in adult primates.
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Advisor:Santos Benito, Fernando F.; Ramón Cueto, Almudena
School:Universitat de València
Source Type:Master's Thesis
Keywords:anatomia i embriologia humana
Date of Publication:05/03/2007