Biology

Research in the field of spinal lesions, supported by the use of several experimental models, represents an “indispensable” choice in order to improve the knowledge of the regenerative and reparative processes of the Central Nervous System and to allow the development of innovative therapeutic strategies of the surgical, cellular and pharmacological type. Indeed, as of today, surgical operations allow only to immobilise the vertebral column, but they do not bring any improvement to the palsy since an effective regeneration of the spinal cord is not possible. Why doesn’t the spinal cord regenerate? What are the factors that hinder a correct and functional regeneration? Numerous and complex molecular and cellular mechanisms contribute to the failure of the axonal regeneration following the damage: the proteins associated to the myeline (the presence of NOGO above all), the settling of extracellular matrix with inhibitory effect in the lesion sites, the lack or considerable shortage of positive environmental stimuli like the ones provided by growth factors. On the basis of the considerations above, although the animal model represents a compulsory stage to study the regeneration of the spinal cord, the detailed understanding of its biological aspects and the set of problems related to the use of ‘in vivo’ models have led scientists to come up with alternative methods. The marrow’s organotypic cultures may be a valid tool to study the axonal regeneration of the spinal damage, proving a useful compromise between the  in vitro studies like that of the cellular cultures and the in vivo ones with the animal model. This type of ex vivo culture indeed allows to control the extracellular environment as well as a repeated access, keeping the morphology and the local synaptic connections in vitro practically intact. The ‘’Giorgio Brunelli Foundation for the research on Spinal Cord Lesions E.S.C.R.I. ONLUS’’, even further to bureaucratic difficulties due to the use of animal experimental models, has decided to take up this course of studies using three elements: platelet preparations, mesenchymal stem cells and nerve growth factors; all this in order to create a microenvironment which favours and allows axonal regeneration capable of contrasting the factors  obstructing it. The platelet concentrates, also called “platelet gels”, represent an innovative and interesting methodology used within the tissue regeneration. Such preparations base their regenerative potentiality on the rich content of growth factors that are necessary to induce cellular proliferation, remodelling of the extracellular matrix and the processes of neovascularisation occurring during the various stages of regeneration of different tissues. The stem cells represent a huge promise to introduce new neurons or glial cells into the damaged nervous system.  Indeed they are a great resource to research and to a potential treatment because of their multi-potentiality, as they can be reproduced in vitro, bound with genetic markers or therapeutic genes implanted in the nervous system. Finally, the neurotrophic factors like the Nerve Growth Factor (NGF), the Brain Derived Neurotrophic Factor (BDNF) and the Neurotrophin-3 (NT-3) play an essential role.  These three elements combined together are used in cultures and in organotypic co-cultures of spinal cord and encephalic cortex of rats  [(a) single slice of spinal cord, (b) co-culture of two slices of spinal cord, (c) co-culture of two slices of cortex and marrow respectively, (d) corticospinal tract in vitro – cortex,bridge,marrow]. So this is the Foundation’s ‘fibre of research’ which, despite the bureaucratic and economic complexities, the hostile  ‘microenvironment’, continues to regenerate and to find solution so as not to put an end to the hope of thousands of patients who see in research itself the only possible answer to their requests. If we could implant this kind of fibre we would not have a problem of spinal lesions anymore.

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