37 research outputs found
Do hypoxia/normoxia culturing conditions change the neuroregulatory profile of Wharton Jelly mesenchymal stem cells secretome?
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. Conventionally, hWJ-MSCs are cultured and characterized under normoxic conditions (21 % oxygen tension), although the oxygen levels within tissues are typically much lower (hypoxic) than these standard culture conditions. Therefore, oxygen tension represents an important environmental factor that may affect the performance of mesenchymal stem cells in vivo. However, the impact of hypoxic conditions on distinct mesenchymal stem cell characteristics, such as the secretome, still remains unclear. Methods: In the present study, we have examined the effects of normoxic (21 % O2) and hypoxic (5 % O2) conditions on the hWJ-MSC secretome. Subsequently, we address the impact of the distinct secretome in the neuronal cell survival and differentiation of human neural progenitor cells. Results: The present data indicate that the hWJ-MSC secretome collected from normoxic and hypoxic conditions displayed similar effects in supporting neuronal differentiation of human neural progenitor cells in vitro. However, proteomic analysis revealed that the use of hypoxic preconditioning led to the upregulation of several proteins within the hWJ-MSC secretome. Conclusions: Our results suggest that the optimization of parameters such as hypoxia may lead to the development of strategies that enhance the therapeutic effects of the secretome for future regenerative medicine studies and applications. © 2015 Teixeira et al.Portuguese Foundation for Science and Technology (FCT) (Ciência 2007
program and IF Development Grant (AJS); and pre-doctoral fellowships to
FGT (SFRH/69637/ 2010) and SIA (SFRH/BD/81495/2011); Canada Research
Chairs (LAB) and a SSE Postdoctoral Fellowship (KMP); The National Mass
Spectrometry Network (RNEM) (REDE/1506/REM/2005); co-funded by Programa
Operacional Regional do Norte (ON.2 – O Novo Norte), ao abrigo do Quadro de
Referência Estratégico Nacional (QREN), através do Fundo Europeu de
Desenvolvimento Regional (FEDER).info:eu-repo/semantics/publishedVersio
Inhibition of Mitochondrial Complex III Blocks Neuronal Differentiation and Maintains Embryonic Stem Cell Pluripotency
The mitochondrion is emerging as a key organelle in stem cell biology, acting as a regulator of stem cell pluripotency
and differentiation. In this study we sought to understand the effect of mitochondrial complex III inhibition during
neuronal differentiation of mouse embryonic stem cells. When exposed to antimycin A, a specific complex III inhibitor,
embryonic stem cells failed to differentiate into dopaminergic neurons, maintaining high Oct4 levels even when
subjected to a specific differentiation protocol. Mitochondrial inhibition affected distinct populations of cells present in
culture, inducing cell loss in differentiated cells, but not inducing apoptosis in mouse embryonic stem cells. A
reduction in overall proliferation rate was observed, corresponding to a slight arrest in S phase. Moreover, antimycin
A treatment induced a consistent increase in HIF-1α protein levels. The present work demonstrates that
mitochondrial metabolism is critical for neuronal differentiation and emphasizes that modulation of mitochondrial
functions through pharmacological approaches can be useful in the context of controlling stem cell maintenance/
differentiation.Fundação para a Ciência e a Tecnologia (FCT) Portugal for grant support (PTDC/EBB-EBI/101114/2008, PTDC/EBB-EBI/
120634/2010 and PDTC/QUI-BIQ/120652/2010 co-funded by Compete/FEDER/National Funds; and a PhD scholarship attributed to SP (SFRH/BD/
37933/2007). Center for Neuroscience and Cell Biology (CNC) funding is also supported by FCT (PEst-C/SAU/LA0001/2011). EA’s work was supported by
the Swedish Foundation for Strategic Research (SRL Program), Swedish Research Council (DBRM), Karolinska Institutet (SFO Thematic Center in Stem
Cells and Regenerative Medicine), and Hjärnfonden