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  • Assessing the Impact of induced mesenchymal stem cells secretome in a 3D in vitro model of Parkinson's disease
    Publication . Barbosa, Catarina Filipa da Cruz; Salgado, António; Nóbrega, Clévio
    Parkinson’s disease (PD) is a complex disease characterized by a loss of dopaminergic (DA) neurons that leads to lifelong motor and non-motor impairments, still with no efficient treatment that can halt or revert its progression. Mesenchymal stem cells (MSCs) have been proposed as a promising therapeutic strategy to prevent dopaminergic neurons degeneration, particularly due to their paracrine action. Induced MSCs (iMSCs), obtained from induced pluripotent stem cells (iPSCs) differentiation, present an advantageous cell source for obtaining large amounts of secretome due to their superior proliferative capacity. In this project, we aimed to (1) develop a 3D in vitro model for the study of PD, (2) compare the long-term culture of iMSCs in either a commercial serum-free (SF) medium or a human platelet lysate (hPL) supplemented medium, (3) compare the effects of secretome from iMSCs expanded in different media and from early and late passages on dopaminergic differentiation, and (4) compare the effects of these secretomes on neuroprotection of a 3D in vitro model of PD. Results showed that the developed 3D collagen model demonstrated a robust network of neurons, that, when challenged with a toxin, resulted in a suitable PD model. hPL supplementation induces a higher proliferative capacity and lower levels of replicative senescence of iMSCs. The proteomic analysis reveals a secretory profile similar between iMSCs cultured in these two media, with a smaller portion of proteins that could be relevant for neuroregenerative processes being differentially expressed between them. Secretome from early passage iMSCs expanded in hPL supplemented medium had a positive impact on dopaminergic differentiation that other secretomes. The impact of these secretomes on the developed 3D model of PD did not show differences. Results show that the modulation of iMSCs secretome through expansion in different media and collection at different cell passages can influence therapeutic potential for PD.
    2023-11-02Master thesis Embargo Show more
  • Combined baclofen with pregabalin administration as a potential therapy for spinal cord injury
    Publication . Ferreira, Marta Raquel Lima; Salgado, António; Sousa, Nídia de; Araújo, Inês
    Spinal cord injury (SCI) is a neurological impairment that hampers the communication between the brain and the rest of the body, resulting in permanent loss of motor function and sensory perception. After the injury, it is initiated a cascade of biological and biochem ical processes. No effective therapy for SCI has yet been developed, however several studies in distinct areas has been developed. The comorbidities that result from a SCI decrease the patient’s quality of life N evertheless, some approved drug can help to control some of these problems, such as baclofen and pregabalin. B aclofen and pregabalin are effective in controlling spasticity and neuropathic pain in people with SCI, but recently they have also been used to as potential therapies to treat the conseque nces induced by SCI. In these studies , it was found that baclofen could improve the locomotor function and act as a neuroprotector. Regarding to pregabalin, it was observed that this drug improve motor function, but could also induce axonal regeneration, a nd protect the spinal cord after an insult. The aim of these study was to evaluat e the effect of a combine baclofen with pregabalin administration after a transected SCI in mice. To do that , it was performed an in vivo experiment during six week, where it was assessed the animals´ behaviour and histological analysis. No motor improvements were observed, however treated animals achieved weight support. On this study one of the treated group s do not exhibit allodynia after SCI, confirmed by v on Frey test. Through the spinal cord tissue analysis, it was observed that the treatment not only promotes a better neuroprotection and an axonal regeneration after SCI, but also appears to induce a more controlled systemic inflammatory response. Overall, o ur study suggests that combined administration of baclofen with pregabalin leads to a neuroprotection and a neuroregeneration after SCI, but further studies need to be done to a better understanding of these strategy.
    2023-11-02Master thesis Open Access Show more