Neutralization of Nerve Growth Factor Impairs Proliferation and Differentiation of Adult Neural Progenitors in the Subventricular Zone

Scardigli, Raffaella; Capelli, P; Vignone, Domenico; Brandi, Rossella; Ceci, Marcello; Regina, Federico La; Piras, Eleonora; Cintoli, Simona; Berardi, Nicoletta; Capsoni, Simona; Cattaneo, Antonino

doi:10.1002/stem.1744

Cited by 30 publications

(28 citation statements)

References 49 publications

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“…NGF (robustly increased in the dynamic CM, Fig. 5C) is considered to be a strong modulator of neurogenesis as well as, to enhance the survival and neuronal/glial maturation47. And finally, IGF-1 (significantly increased in the dynamic CM, Fig.…”

Section: Discussionmentioning

confidence: 97%

Modulation of the Mesenchymal Stem Cell Secretome Using Computer-Controlled Bioreactors: Impact on Neuronal Cell Proliferation, Survival and Differentiation

Teixeira

Panchalingam

Assunção‐Silva

et al. 2016

Sci Rep

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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 hypothesis that one can modulate its secretome through their use. Herein, we present data indicating that the use of computer-controlled suspension bioreactors enhanced the neuroregulatory profile of hMSCs secretome. Indeed, higher levels of in vitro neuronal differentiation and NOTCH1 expression in human neural progenitor cells (hNPCs) were observed when these cells were incubated with the secretome of dynamically cultured hMSCs. A similar trend was also observed in the hippocampal dentate gyrus (DG) of rat brains where, upon injection, an enhanced neuronal and astrocytic survival and differentiation, was observed. Proteomic analysis also revealed that the dynamic culturing of hMSCs increased the secretion of several neuroregulatory molecules and miRNAs present in hMSCs secretome. In summary, the appropriate use of dynamic culture conditions can represent an important asset for the development of future neuro-regenerative strategies involving the use of hMSCs secretome.

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Section: Discussionmentioning

confidence: 97%

Modulation of the Mesenchymal Stem Cell Secretome Using Computer-Controlled Bioreactors: Impact on Neuronal Cell Proliferation, Survival and Differentiation

Teixeira

Panchalingam

Assunção‐Silva

et al. 2016

Sci Rep

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“…Exogenous mature NGF positively affects adult hippocampal neural precursor survival and consequently hippocampal neurogenesis in physiological and neurodegenerative conditions . A more direct positive effect of NGF on adult subventricular zone (SVZ) neurogenesis has been recently shown by our group, as we demonstrated that NGF neutralization impairs both proliferation and neuronal differentiation of SVZ progenitors . For what concerns proneurotrophins, a role in cell cycle modulation has only recently being uncovered , but their function in this context needs further direct investigations.…”

Section: Introductionmentioning

confidence: 71%

“…Neural stem cell cultures from single HP were performed as described . Six‐month‐old mice (WT or AD11) were anesthetized as described before and killed by decapitation.…”

Section: Methodsmentioning

confidence: 99%

“…Cells were isolated by enzymatic digestion (1.33 mg/ml trypsin, 0.7 mg/ml hyaluronidase, and 0.2 mg/ml kynurenic acid; Sigma–Aldrich) for 30 minutes at 37°C and mechanical dissociation with small‐bore Pasteur pipette. Cells were plated at 5 × 10 3 cells per cm 2 cells density and cultured in Dulbecco's modified Eagle's medium (DMEM)/F12 medium supplemented with B27 (Invitrogen, San Diego, CA), epidermal growth factor (EGF), and basic fibroblast growth factor (bFGF) (20 and 10 ng/ml, respectively; Peprotech, London, UK; NSC growth medium) in a humidified incubator at 37°C in 5% CO 2 for 3 weeks. Growth factors were replenished weekly.…”

Section: Methodsmentioning

confidence: 99%

“…Neurotrophins have been shown to regulate neurogenesis during embryonic development . Instead, little is known about the relevance of NTs family members in regulating aNSCs biology , in which the cell‐cycle progression or exit of the aNSCs must be tightly regulated. In addition to survival‐inducing activity, NTs can be potent regulators of cell cycle , which could be potentially very relevant for their actions on aNSCs.…”

Section: Introductionmentioning

confidence: 99%

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ProNGF Is a Cell-Type-Specific Mitogen for Adult Hippocampal and for Induced Neural Stem Cells

et al. 2019

Self Cite

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The role of proNGF, the precursor of nerve growth factor (NGF), in the biology of adult neural stem cells (aNSCs) is still unclear. Here, we analyzed adult hippocampal neurogenesis in AD11 transgenic mice, in which the constitutive expression of anti-NGF antibody leads to an imbalance of proNGF over mature NGF. We found increased proliferation of progenitors but a reduced neurogenesis in the AD11 dentate gyrus (DG)-hippocampus (HP). Also in vitro, AD11 hippocampal neural stem cells (NSCs) proliferated more, but were unable to differentiate into morphologically mature neurons. By treating wild-type hippocampal progenitors with the uncleavable form of proNGF (proNGF-KR), we demonstrated that proNGF acts as mitogen on aNSCs at low concentration. The mitogenic effect of proNGF was specifically addressed to the radial glia-like (RGL) stem cells through the induction of cyclin D1 expression. These cells express high levels of p75 NTR , as demonstrated by immunofluorescence analyses performed ex vivo on RGL cells isolated from freshly dissociated HP-DG or selected in vitro from NSCs by leukemia inhibitory factor. Clonogenic assay performed in the absence of mitogens showed that RGLs respond to proNGF-KR by reactivating their proliferation and thus leading to neurospheres formation. The mitogenic effect of proNGF was further exploited in the expansion of mouse-induced neural stem cells (iNSCs). Chronic exposure of iNSCs to proNGF-KR increased their proliferation. Altogether, we demonstrated that proNGF acts as mitogen on hippocampal and iNSCs. STEM CELLS 2019;37:1223-1237 SIGNIFICANCE STATEMENTTo the authors' knowledge, this work identifies for the first time a new role of proNGF as a specific mitogenic factor for the proliferation of adult hippocampal neural stem cells and in induced neural stem cells. The relevance of this finding is that it adds new knowledge to the complex picture of neural stem cells biology and indicates proNGF/NGF balance critical for adult hippocampal neurogenesis. In addition, the results open new perspectives in the view of developing future therapeutic approaches based on the stimulation of endogenous adult neurogenesis or on cell-reprogramming protocols.Stereological analysis of the number of cells was performed on series of 40-μm free-floating coronal sections of the entire DG of the HP, which were analyzed by confocal microscopy to www.StemCells.com

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Nanocellulose‐Reinforced Hydroxyapatite Nanobelt Membrane as a Stem Cell Multi‐Lineage Differentiation Platform for Biomimetic Construction of Bioactive 3D Osteoid Tissue In Vitro

Liu

Wei²,

Xu³

et al. 2020

Adv Healthcare Materials

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Severe bone defects, especially accompanied by vascular and peripheral nerve injuries, remain a massive challenge. Most studies related to bone tissue engineering have focused on osteogenic differentiation of mesenchymal stem cells (MSCs), and ignored the formation of blood vessels and nerves in the newly generated bone owing to the lack of proper materials and methodology for tuning stem cells differentiated into osteogenic, neuronal, and endothelial cells (ECs) in the same scaffold system. Herein, a nanocellulose-reinforced hybrid membrane with good mechanical properties and control over biodegradation by assembling ultralong hydroxyapatite nanobelts in a bacterial nanocellulose hydrogel is designed and synthesized. Osteogenic, neuronal cells are successfully differentiated on this hybrid membrane. Based on the multi-lineage differentiation property of the membrane, a bioactive 3D osteoid tissue (osteogenic, neural, and ECs) is mimetically constructed in vitro using layer-by-layer culture and integration. The bone regeneration ability of the as-prepared bioactive osteoid tissue is assessed in vivo via heterotopic osteogenesis experiments for eight weeks. The rapid new bone growth and formation of blood capillaries and nerve fibers prove that the hybrid membrane can be universally applied as a stem cell multi-lineage differentiation platform, which has significant applications in bone tissue engineering.

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Neutralization of Nerve Growth Factor Impairs Proliferation and Differentiation of Adult Neural Progenitors in the Subventricular Zone

Cited by 30 publications

References 49 publications

Modulation of the Mesenchymal Stem Cell Secretome Using Computer-Controlled Bioreactors: Impact on Neuronal Cell Proliferation, Survival and Differentiation

Modulation of the Mesenchymal Stem Cell Secretome Using Computer-Controlled Bioreactors: Impact on Neuronal Cell Proliferation, Survival and Differentiation

ProNGF Is a Cell-Type-Specific Mitogen for Adult Hippocampal and for Induced Neural Stem Cells

Nanocellulose‐Reinforced Hydroxyapatite Nanobelt Membrane as a Stem Cell Multi‐Lineage Differentiation Platform for Biomimetic Construction of Bioactive 3D Osteoid Tissue In Vitro

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