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Glial-restricted precursors stimulate endogenous cytogenesis and effectively re...

Martins-Macedo, Joana; Araújo, Bruna; Anjo, Sandra I.; Silveira-Rosa, Tiago; Patrício, Patrícia; Alves, Nuno Dinis; Silva, Joana M.; Teixeira, Fábio G.

Adult cytogenesis, the continuous generation of newly-born neurons (neurogenesis) and glial cells (gliogenesis) throughout life, is highly impaired in several neuropsychiatric disorders, such as Major Depressive Disorder (MDD), impacting negatively on cognitive and emotional domains. Despite playing a critical role in brain homeostasis, the importance of gliogenesis has been overlooked, both in healthy and dise...


Pre-clinical assessment of Roflumilast therapy in a thoracic model of spinal co...

Sousa, Carla S.; Lima, Rui Augusto Ribeiro; Cibrão, Jorge R.; Gomes, Eduardo D.; Fernandes, Luís S.; Pinho, Tiffany Santos; Silva, Deolinda

The failure of axons to regenerate after a spinal cord injury (SCI) remains one of the greatest challenges in neuroscience. The initial mechanical trauma is followed by a secondary injury cascade, creating a hostile microenvironment, which not only is not permissive to regeneration but also leads to further damage. One of the most promising approaches for promoting axonal regeneration is to maintain the levels ...


Bone Marrow Mesenchymal Stem Cells' Secretome Exerts Neuroprotective Effects in...

Mendes-Pinheiro, Bárbara; Anjo, Sandra I.; Manadas, Bruno; Da Silva, Jorge D.; Marote, Ana; Behie, Leo A.; Teixeira, Fábio G.; Salgado, António J.

Parkinson's disease (PD) is characterized by a selective loss of dopamine (DA) neurons in the human midbrain causing motor dysfunctions. The exact mechanism behind dopaminergic cell death is still not completely understood and, so far, no cure or neuroprotective treatment for PD is available. Recent studies have brought attention to the variety of bioactive molecules produced by mesenchymal stem cells (MSCs), g...


Secretome of Undifferentiated Neural Progenitor Cells Induces Histological and ...

Mendes-Pinheiro, Bárbara; Teixeira, Fábio G.; Anjo, Sandra I.; Manadas, Bruno; Behie, Leo A.; Salgado, António J.

Parkinson's disease (PD) is a progressive neurodegenerative movement disorder that results from the death of dopamine (DA) neurons. Over recent years, differentiated or undifferentiated neural stem cells (NSCs) transplantation has been widely used as a means of cell replacement therapy. However, compelling evidence has brought attention to the array of bioactive molecules produced by stem cells, defined as secr...


Crosstalk between glial and glioblastoma cells triggers the "go-or-grow" phenot...

Oliveira, Ana Isabel; Anjo, Sandra I.; Vieira de Castro, Joana; Serra, Sofia C.; Salgado, António J.; Manadas, Bruno; Costa, Bruno M.

Background: Glioblastoma (GBM), the most malignant primary brain tumor, leads to poor and unpredictable clinical outcomes. Recent studies showed the tumor microenvironment has a critical role in regulating tumor growth by establishing a complex network of interactions with tumor cells. In this context, we investigated how GBM cells modulate resident glial cells, particularly their paracrine activity, and how th...


Impact of mesenchymal stem cells' secretome on glioblastoma pathophysiology

Vieira de Castro, Joana; Gomes, Eduardo D.; Granja, Sara; Anjo, Sandra I.; Baltazar, Fátima; Manadas, Bruno; Salgado, António J.; Costa, Bruno M.

Background: Glioblastoma (GBM) is a highly aggressive primary brain cancer, for which curative therapies are not available. An emerging therapeutic approach suggested to have potential to target malignant gliomas has been based on the use of multipotent mesenchymal stem cells (MSCs), either unmodified or engineered to deliver anticancer therapeutic agents, as these cells present an intrinsic capacity to migrate...


Mesenchymal stem cells secretome-induced axonal outgrowth is mediated by BDNF

Martins, Luís F.; Costa, Rui O.; Pedro, Joana R.; Aguiar, Paulo; Serra, Sofia C.; Teixeira, Fabio G.; Sousa, Nuno; Salgado, António J.

Mesenchymal stem cells (MSCs) have been used for cell-based therapies in regenerative medicine, with increasing importance in central and peripheral nervous system repair. However, MSCs grafting present disadvantages, such as, a high number of cells required for transplantation and low survival rate when transplanted into the central nervous system (CNS). In line with this, MSCs secretome which present on its c...


Impact of the Secretome of Human Mesenchymal Stem Cells on Brain Structure and ...

Teixeira, Fábio G.; Carvalho, Miguel M.; Panchalingam, Krishna M.; Rodrigues, Ana J.; Mendes-Pinheiro, Bárbara; Anjo, Sandra I.; Manadas, Bruno

Research in the last decade strongly suggests that mesenchymal stem cell (MSC)-mediated therapeutic benefits are mainly due to their secretome, which has been proposed as a possible therapeutic tool for the treatment of Parkinson's disease (PD). Indeed, it has been shown that the MSC secretome increases neurogenesis and cell survival, and has numerous neuroprotective actions under different conditions. Addition...


Modulation of the Mesenchymal Stem Cell Secretome Using Computer-Controlled Bio...

Teixeira, Fábio G.; Panchalingam, Krishna M.; Assunção-Silva, Rita; Serra, Sofia C.; Mendes-Pinheiro, Bárbara; Patrício, Patrícia; Jung, Sunghoon

In recent years it has been shown that the therapeutic benefits of human mesenchymal stem/stromal cells (hMSCs) in the Central Nervous System (CNS) are mainly attributed to their secretome. The implementation of computer-controlled suspension bioreactors has shown to be a viable route for the expansion of these cells to large numbers. As hMSCs actively respond to their culture environment, there is the hypothes...


Do hypoxia/normoxia culturing conditions change the neuroregulatory profile of ...

Teixeira, Fábio G; Panchalingam, Krishna M; Anjo, Sandra Isabel; Manadas, Bruno; Pereira, Ricardo; Sousa, Nuno; Salgado, António J.; Behie, Leo A

Introduction: The use of human umbilical cord Wharton Jelly-derived mesenchymal stem cells (hWJ-MSCs) has been considered a new potential source for future safe applications in regenerative medicine. Indeed, the application of hWJ-MSCs into different animal models of disease, including those from the central nervous system, has shown remarkable therapeutic benefits mostly associated with their secretome. Conven...


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