Induction of neurite outgrowth in 3D hydrogel-based environments

Assunção‐Silva, Rita C.; Oliveira, Cátia; Ziv-Polat, Ofra; Gomes, Eduardo D.; Sahar, Abraham; Sousa, Nuno; Silva, Nuno; Salgado, António J.

doi:10.1088/1748-6041/10/5/051001

Cited by 16 publications

(8 citation statements)

References 36 publications

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“…To date, several groups have demonstrated that transplantation of MSCs into spinal cord favors nerve regeneration 5–9 . Moreover, recent studies suggest that MSCs secretome promotes neurite outgrowth 10, 13, 29 . However, it remained unknown the effects of mesenchymal stem cells secretome in CNS neurons, specifically in the axons.…”

Section: Discussionmentioning

confidence: 99%

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

Martins

Costa

Pedro

et al. 2017

Sci Rep

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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 composition a wide range of molecules (neurotrophins, cytokines) and microvesicles, can be a solution to surpass these problems. However, the effect of MSCs secretome in axonal elongation is poorly understood. In this study, we demonstrate that application of MSCs secretome to both rat cortical and hippocampal neurons induces an increase in axonal length. In addition, we show that this growth effect is axonal intrinsic with no contribution from the cell body. To further understand which are the molecules required for secretome-induced axonal outgrowth effect, we depleted brain-derived neurotrophic factor (BDNF) from the secretome. Our results show that in the absence of BDNF, secretome-induced axonal elongation effect is lost and that axons present a reduced axonal growth rate. Altogether, our results demonstrate that MSCs secretome is able to promote axonal outgrowth in CNS neurons and this effect is mediated by BDNF.

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Section: Discussionmentioning

confidence: 99%

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

Martins

Costa

Pedro

et al. 2017

Sci Rep

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“…Dorsal root ganglion explants were used for axonal growth experiments. For that, DRGs from 5 days-old neonatal Wistar-Han rat pups were dissected as previously described [33]. Briefly, DRGs from cervical and thoracic regions of the spine of neonatal rat pups (P5) were dissected and the remnants of peripheral nerve processes were cleaned.…”

Section: Isolation and Culture Of Dorsal Root Ganglion (Drg) Explantsmentioning

confidence: 99%

Exploiting the impact of the secretome of MSCs isolated from different tissue sources on neuronal differentiation and axonal growth

et al. 2018

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Cell transplantation using Mesenchymal stem cell (MSC) secretome have recently been presented as a possible free-based therapy for CNS related disorders. MSC secretome is rich in several bio-factors that act synergically towards the repair of damaged tissues, thus making it an ideal candidate for regenerative applications. Great effort is currently being made to map the molecules that compose the MSC secretome. Previous proteomic characterization of the secretome (in the form of conditioned media - CM) of MSCs derived from adipose tissue (ASC), bone-marrow (BMSC) and umbilical cord (HUCPVC) was performed by our group, where proteins relevant for neuroprotection, neurogenic, neurodifferentiation, axon guidance and growth functions were identified. Moreover, we have found significant differences among the expression of several molecules, which may indicate that their therapeutic outcome might be distinct. Having this in mind, in the present study, the neuroregulatory potential of ASC, BMSC and HUCPVC CM in promoting neurodifferentiation and axonal outgrowth was tested in vitro, using human telencephalon neuroprogenitor cells and dorsal root ganglion explants, respectively. The CM from the three MSC populations induced neuronal differentiation from human neural progenitor cells, as well as neurite outgrowth from dorsal root ganglion explants. Moreover, all the MSC populations promoted the same extent of neurodifferentiation, while ASC CM demonstrated higher potential in promoting axonal growth.

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“…Quantitative assessment of the neurite outgrowth in these assays includes parameters, such as the number of neurites, neurite orientation, and neurite length. Recently, neurite outgrowth in 3D hydrogel-based environments has also been established (Assuncao- Silva et al 2015), allowing to culture neuronal progenitors under diff erent conditions and analyze survival, diff erentiation, and neurite outgrowth (Cruz Gaitan et al 2015).…”

Section: Origin Of Neuritesmentioning

confidence: 99%

Mechanisms involved in the regulation of neuropeptide-mediated neurite outgrowth: a minireview

Lestanova

Bačová

Bakoš

2016

Endocrine Regulations

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Th e present knowledge, regarding the neuronal growth and neurite extension, includes neuropeptide action in the central nervous system. Research reports have brought much information about the multiple intracellular signaling pathways of neuropeptides. However, regardless of the diff erences in the local responses elicited by neuropeptides, there exist certain functional similarities in the eff ects of neuropeptides, mediated by their receptors. In the present review, data of the relevant studies, focused on G protein-coupled receptors activated by neuropeptides, are summarized. Particularly, receptors that activate phosphatidylinositol-calcium system and protein kinase C pathways, resulting in the reorganization of the neuronal cytoskeleton and changes in the neuronal morphology, are discussed. Based on our data received, we are showing that oxytocin increases the gene expression of GTPase cell division cycle protein 42 (Cdc42), implicated in many aspects of the neuronal growth and morphology. We are also paying a special attention to neurite extension and retraction in the context of neuropeptide regulation.

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Induction of neurite outgrowth in 3D hydrogel-based environments

Cited by 16 publications

References 36 publications

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

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

Exploiting the impact of the secretome of MSCs isolated from different tissue sources on neuronal differentiation and axonal growth

Mechanisms involved in the regulation of neuropeptide-mediated neurite outgrowth: a minireview

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