Speaker
Description
The low regeneration potential of the central nervous system (CNS) represents a challenge for the development of new therapeutic strategies. Mesenchymal stem cells (MSCs) have been proposed as a possible therapeutic tool for CNS disorders, namely due to the beneficial actions of their secretome. Indeed, the latter possesses a broad range of neuroregulatory factors that promote an increase in neurogenesis, inhibition of apoptosis/glial scar, immunomodulation, angiogenesis, neuronal and glial cell survival, as well as relevant neuroprotective actions into different pathophysiological contexts. Considering their protective action in lesioned sites, MSCs, and their secretome, might also improve the integration of local progenitor cells in neuroregeneration processes. In this sense their use could represent an important vehicle for the establishment of future CNS regenerative therapies. In the present talk the role of MSCs, and their secretome, on phenomena such as in vitro and in vivo neuronal/glial survival will be addressed. Additionally, their possible applications, for Spinal Cord Injury and nerve repair be presented. For several years we have been dissecting the role of the secretome of adipose tissue derived stem cells (ASCs), as well as its individual vesicular and proteic individual fractions, in in vitro and in vivo models of axonal growth, inflammation and spinal cord injury, respectively. In vitro experiments revealed that the unfractionated secretome had a significant effect growth, when compared to its protein or vesicular fractions, on axonal growth and neuroinflammatory profile of microglial cells. Following on this data we then evaluated the impact of ASCs secretome on the histological and functional recovery of transection and compression based models of SCI in mice. Results of these experiments revealed that ASCs secretome induced a significant improvement of the locomotor performance of SCI mice, when compared to untreated animals, as assessed by the Basso Mouse Scale test (BMS). This was particular evident in the animals that were injected systemically (IV through the tail veins) with ASCs secretome, when compared to a local delivery. Additionally, the histological analysis has indicated that this motor improvement is closely related with a consistent reduction of the lesion volume, as well as a decreased activation of inflammatory cells (microglia) activation after treatment, as well as an robust increase on the regeneration of new axons. Finally we have also developed approaches for the encpasulation of the secretome in biodegradble systems to facilitate and potentiate their local application.
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