Mesenchymal stem cell secretome induces synapse formation in central nervous system neurons
Autor(a) principal: | |
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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 |
Resumo: | 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. |
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Mesenchymal stem cell secretome induces synapse formation in central nervous system neuronsMesenchymal stem cellsSecretomeSynapse formationSynaptogenesisMitochondriaMesenchymal 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.As células estaminais mesenquimais (em inglês, MSCs, “mesenchymal stem cells”) têm sido o alvo de extensa investigação devido ao seu efeito protetor, trófico em populações neuronais, capacidade de regular o sistema imune, potencial de diferenciação e baixa tumorigenicidade, tornando-as uma fonte atrativa para terapias celulares. Para além da sua capacidade de diferenciação em progenitores neurais, estudos recentes têm demonstrado que elas exercem um efeito parácrino no microambiente e nas células que as rodeiam, que é responsável pelos seus efeitos benéficos. O conjunto de fatores de crescimento, citocinas, quimiocinas, moléculas de adesão celular, hormonas, exosomas, microvesículas, mediadores lipídicos e ácidos nucleicos livres que são excretados pelas MSCs para o meio de cultura, é considerado o secretoma. Curiosamente, diferentes secretomas originários de nichos celulares diferentes têm demonstrado que são capazes de exercer uma ação protetora e regenerativa nos neurónios em diferentes condições do sistema nervoso, incluindo na lesão da medula espinal. Apesar dos ligeiros melhoramentos na recuperação funcional obtidos em ensaios clínicos com MSCs, os mecanismos responsáveis por esta ação regenerativa permanecem desconhecidos. Estudos recentes têm demonstrado que o secretoma das MSCs induz um crescimento das neurites e promove a sobrevivência celular. Contudo, o seu efeito na formação de sinapses não é conhecido. Para preencher esta lacuna no conhecimento, neste trabalho foi avaliado o efeito do secretoma, obtido a partir de duas populações de células estaminais mesenquimais, as células perivasculares do cordão umbilical (em inglês, human umbilical cord perivascular cells, HUCPVCs) e as células estaminais mesenquimais da medula óssea (em inglês, bone marrow-mesenchymal stem cells, BM-MSCs), na diferenciação pré-sináptica em neurónios do sistema nervoso central. Verificamos que o secretoma destas duas populações de MSCs induz a aglomeração de vesículas sinápticas em neurónios corticais. Para além disso, observamos um efeito semelhante em neurónios hipocampais. Realizámos também uma análise preliminar do efeito do secretoma das MSCs na dinâmica e biogénese da mitocôndria, um organelo crucial em todas as fases do desenvolvimento neuronal assim como na regeneração axonal. Em conjunto, os resultados demonstram que o secretoma obtidos a partir das HUCPVCs e BM-MSCs, são promotores da formação de sinapses em neurónios do sistema nervoso central. Estes resultados sugerem ainda um possível papel do secretoma na regulação da biogénese e dinâmica mitocondrial, criando uma base para estudos futuros que abordem os mecanismos responsáveis por estes processos. Estas propriedades tornam o secretomas das MSCs um possível candidato para futura investigação na área da medicina regenerativa.2023-03-03T00:00:00Z2021-02-23T00:00:00Z2021-02-23info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10773/30876engFaria, Ricardo Araújoinfo:eu-repo/semantics/embargoedAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-02-22T11:59:40Zoai:ria.ua.pt:10773/30876Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:02:52.101914Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Mesenchymal stem cell secretome induces synapse formation in central nervous system neurons |
title |
Mesenchymal stem cell secretome induces synapse formation in central nervous system neurons |
spellingShingle |
Mesenchymal stem cell secretome induces synapse formation in central nervous system neurons Faria, Ricardo Araújo Mesenchymal stem cells Secretome Synapse formation Synaptogenesis Mitochondria |
title_short |
Mesenchymal stem cell secretome induces synapse formation in central nervous system neurons |
title_full |
Mesenchymal stem cell secretome induces synapse formation in central nervous system neurons |
title_fullStr |
Mesenchymal stem cell secretome induces synapse formation in central nervous system neurons |
title_full_unstemmed |
Mesenchymal stem cell secretome induces synapse formation in central nervous system neurons |
title_sort |
Mesenchymal stem cell secretome induces synapse formation in central nervous system neurons |
author |
Faria, Ricardo Araújo |
author_facet |
Faria, Ricardo Araújo |
author_role |
author |
dc.contributor.author.fl_str_mv |
Faria, Ricardo Araújo |
dc.subject.por.fl_str_mv |
Mesenchymal stem cells Secretome Synapse formation Synaptogenesis Mitochondria |
topic |
Mesenchymal stem cells Secretome Synapse formation Synaptogenesis Mitochondria |
description |
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. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-02-23T00:00:00Z 2021-02-23 2023-03-03T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
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masterThesis |
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publishedVersion |
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http://hdl.handle.net/10773/30876 |
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http://hdl.handle.net/10773/30876 |
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eng |
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eng |
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info:eu-repo/semantics/embargoedAccess |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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