Search

Neural transplantation is a promising therapeutic approach for neurodegenerative diseases; however, many patients receiving intracerebral fetal allografts exhibit signs of immunization to donor antigens that could compromise the graft. In this context, we intracerebrally transplanted mesencephalic pig xenografts into primates to identify a suitable strategy to enable long‐term cell survival, maturation, and differentiation. Parkinsonian primates received WT or CTLA4‐Ig transgenic porcine xenografts and different durations of peripheral immunosuppression to test whether systemic plus graft‐mediated local immunosuppression might avoid rejection. A striking recovery of spontaneous locomotion was observed in primates receiving systemic plus local immunosuppression for 6 mo. Recovery was associated with restoration of dopaminergic activity detected both by positron emission tomography imaging and histological examination. Local infiltration by T cells and CD80/86+ microglial cells expressing indoleamine 2,3‐dioxigenase were observed only in CTLA4‐Ig recipients. Results suggest that in this primate neurotransplantation model, peripheral immunosuppression is indispensable to achieve the long‐term survival of porcine neuronal xenografts that is required to study the beneficial immunomodulatory effect of local blockade of T cell costimulation. The intragraft expression of CTLA4‐Ig, a costimulation blocker, and the duration of the peripheral immunosuppressive treatment can improve cell survival and delay local xenogeneic T cell activation following intracerebral transplantation of transgenic CTLA4‐Ig+/+ pig xenografts in parkinsonian nonhuman primates.

Neural transplantation is a promising therapeutic approach for neurodegenerative diseases; however, many patients receiving intracerebral fetal allografts exhibit signs of immunization to donor antigens that could compromise the graft. In this context, we intracerebrally transplanted mesencephalic pig xenografts into primates to identify a suitable strategy to enable long‐term cell survival, maturation, and differentiation. Parkinsonian primates received WT or CTLA4‐Ig transgenic porcine xenografts and different durations of peripheral immunosuppression to test whether systemic plus graft‐mediated local immunosuppression might avoid rejection. A striking recovery of spontaneous locomotion was observed in primates receiving systemic plus local immunosuppression for 6 mo. Recovery was associated with restoration of dopaminergic activity detected both by positron emission tomography imaging and histological examination. Local infiltration by T cells and CD80/86+ microglial cells expressing indoleamine 2,3‐dioxigenase were observed only in CTLA4‐Ig recipients. Results suggest that in this primate neurotransplantation model, peripheral immunosuppression is indispensable to achieve the long‐term survival of porcine neuronal xenografts that is required to study the beneficial immunomodulatory effect of local blockade of T cell costimulation.

Osteoporotic vertebral compression fractures (VCFs) are an increasing public health problem. Recently, randomised controlled trials on the use of kyphoplasty and vertebroplasty in the treatment of these fractures have been published, but no definitive conclusions have been reached on the role of these interventions. The major problem encountered when trying to perform a meta-analysis of the available studies for the use of cementoplasty in patients with a VCF is that conservative management has not been standardised. Forms of conservative treatment commonly used in these patients include bed rest, analgesic medication, physiotherapy and bracing. In this review, we report the best evidence available on the conservative care of patients with osteoporotic VCFs and associated back pain, focusing on the role of the most commonly used spinal orthoses. Although orthoses are used for the management of these patients, to date, there has been only one randomised controlled trial published evaluating their value. Until the best conservative management for patients with VCFs is defined and standardised, no conclusions can be drawn on the superiority or otherwise of cementoplasty techniques over conservative management.

Cervical spinal disc replacement is used in the management of degenerative cervical disc disease in an attempt to preserve cervical spinal movement and to prevent adjacent disc overload and subsequent degeneration. A large number of patients have undergone cervical spinal disc replacement, but the effectiveness of these implants is still uncertain. In most instances, degenerative change at adjacent levels represents the physiological progression of the natural history of the arthritic disc, and is unrelated to the surgeon. Complications of cervical disc replacement include loss of movement from periprosthetic ankylosis and ossification, neurological deficit, loosening and failure of the device, and worsening of any cervical kyphosis. Strict selection criteria and adherence to scientific evidence are necessary. Only prospective, randomised clinical trials with long-term follow-up will establish any real advantage of cervical spinal disc replacement over fusion.

Cationic liposomes are generally considered as the non-viral counterparts of the more common viral vectors used in several gene therapy protocols, but their use as delivery vehicles is limited by their efficiency even if they display a lower toxicity. However, cationic liposomes are promising delivery systems in cell biology due to their ability to incorporate small molecules into their inner aqueous spheres and to deliver them into cells. Additionally, on the external surface they can bind therapeutic molecules such as nucleic acids, oligonucleotides, plasmids, etc. through electrostatic interactions. The aim of this work was to study the diffusion properties of such vehicles in vivowith a non-invasive technique and to monitor their tissue migration in order to collect information to be further used in gene therapy procedures. For this purpose, cationic liposomes containing the paramagnetic contrast agent Gd(DTPA)2-(Gd(III)-diethylenetriamine-N,N,N′,N″,N″-pentaacetic acid) were investigated because of their extended paramagnetic persistency in vivo, compared to the use of the contrast agent alone, and they were used to monitor the diffusion of such vehicles in an animal model (rat model). In particular, these vectors were injected into the rat brain through a stereotactic frame in a preformed cavity mimicking the lesion which had originated after surgical removal of the primary tumor. For the purpose of comparison, the same injection procedure was also applied to a control series of animals without a preformed brain lesion. Pattern diffusion and steadiness of the reported paramagnetic cationic liposomes were studied by means of Magnetic Resonance Imaging (MRI) which allowed us to monitor their diffusion and assess their intracerebral time availability up to 24 hours.

A new technique for preparing primary tissue cultures by mechanical cell dispersion was idealized. The time required to prepare a culture by this procedure was greatly reduced and the cultures obtained are morphologically and physiologically of better quality than that obtained by the classical methods of enzymatic cell dispersion.