Mesenchymal stem cell secretome induces synapse formation in central nervous system neurons

• Autor(a) principal: Faria, Ricardo Araújo
• Data de Publicação: 2021
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10773/30876
• topic: Mesenchymal stem cells; Secretome; Synapse formation; Synaptogenesis; Mitochondria

Mesenchymal stem cells (MSCs) have been the target of extensive research due to their neuroprotection and neurotrophic effects, immunomodulatory action, differentiation potential and low tumorigenicity making them an attractive source for cell-based therapies. In addition to their ability to differentiate into neural progenitors, recent studies have shown that they exert a paracrine effect in the microenvironment and surrounding cells that is responsible for its beneficial effects. The array of growth factors, cytokines, chemokines, cell adhesion molecules, hormones, exosomes, microvesicles, lipid mediators and free nucleic acids secreted by the MSCs to the culture medium is considered the secretome. Interestingly, different secretomes originated from different cell niches have shown to exhibit a neuroprotective and pro-regenerative action in several neurological disorders, including the spinal cord injury. Despite mild improvements in functional recovery obtained in MSCs clinical trials, the mechanisms responsible for its regenerative action remain elusive. Recent studies have shown that the MSCs’ secretome induces neurite outgrowth and promotes cell survival. However, its effect on synapse formation is currently unknown. To address this gap, we evaluated the effect of the secretome originated from two MSC populations, the human umbilical cord perivascular cells (HUCPVC) and bone marrow-mesenchymal stem cells (BM-MSCs) on presynaptic differentiation of central nervous system neurons. We verified that the secretome of these two populations of MSC induce synaptic vesicle clustering in cortical neurons. Also, we observed a similar effect in hippocampal neurons. Furthermore, we performed a preliminary analysis of the effect of MSC secretome on mitochondria dynamics and biogenesis, an organelle imperative in all stages of neuronal development as well as in axonal regeneration. Taken together, our results show that the secretomes originated from HUCPVCs and BM-MSCs are inducers of synapse formation in neurons of the central nervous system. These results also suggest a possible role in the regulation of mitochondria biogenesis and dynamics, creating a steppingstone for future studies addressing the mechanisms that underlie these processes. These properties render the secretome of MSCs a strong candidate for future research in regenerative medicine.