Novel subventricular zone early progenitor cell-specific adenovirus for in vivo therapy of central nervous system disorders reinforces brain stem cell heterogeneity

Reetz, Julia; Hildebrandt, Steve; Schmidt, Antje; Meier, Claudia; Herchenröder, Ottmar; Gläser, Anne; Witt, Martin; Pützer, Brigitte M.; Wree, Andreas

doi:10.1007/s00429-015-1025-8

Cited by 8 publications

(7 citation statements)

References 51 publications

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“…Corroborating these findings, transthyretin (TTR), a thyroid hormone transporter predominantly produced by the CP [112], exhibits a gender-specific role in the control of neurogenesis in the SVZ that is restricted to a specific subdomain of the SVZ [181], which is in line with the gender-based differences in CP-derived TTR levels detected in the CSF [71,182]. Molecular heterogeneity linked to the receptor repertoire can be also observed between SVZ and SGZ, indicating intrinsic differences in the sensitivity of adult germinal centres to signalling factors presented via CSF [183,184]. This is supported by recent finding showing expression of LRP2, receptor for various morphogens, including BMPs and Wnts that were previously detected in CSF, to be restricted only to SVZ and devoid from SGZ.…”

Section: The Target Brain Regions Of Cp-csf Signallingsupporting

confidence: 60%

Choroid Plexus: The Orchestrator of Long-Range Signalling Within the CNS

Kaiser

Bryja

2020

IJMS

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Cerebrospinal fluid (CSF) is the liquid that fills the brain ventricles. CSF represents not only a mechanical brain protection but also a rich source of signalling factors modulating diverse processes during brain development and adulthood. The choroid plexus (CP) is a major source of CSF and as such it has recently emerged as an important mediator of extracellular signalling within the brain. Growing interest in the CP revealed its capacity to release a broad variety of bioactive molecules that, via CSF, regulate processes across the whole central nervous system (CNS). Moreover, CP has been also recognized as a sensor, responding to altered composition of CSF associated with changes in the patterns of CNS activity. In this review, we summarize the recent advances in our understanding of the CP as a signalling centre that mediates long-range communication in the CNS. By providing a detailed account of the CP secretory repertoire, we describe how the CP contributes to the regulation of the extracellular environment—in the context of both the embryonal as well as the adult CNS. We highlight the role of the CP as an important regulator of CNS function that acts via CSF-mediated signalling. Further studies of CP–CSF signalling hold the potential to provide key insights into the biology of the CNS, with implications for better understanding and treatment of neuropathological conditions.

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Section: The Target Brain Regions Of Cp-csf Signallingsupporting

confidence: 60%

Choroid Plexus: The Orchestrator of Long-Range Signalling Within the CNS

Kaiser

Bryja

2020

IJMS

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“…Peptides can be selected in a relatively cost-effective manner using phage display 5–9 . This powerful technology was first introduced in 1985 10 and has been modified to a rapid high-throughput one step method - Biopanning and Rapid Analysis of Selective Interactive Ligands (BRASIL) 11 , which has enabled the construction of a large number of phage peptide libraries, with a wide range of applications 12–15 . The phage display screening methodology has been exploited and applied in cancer progression and used in selection processes, not only on solid primary tumors, but also on tumor vasculature, metabolism, cell signaling targets and metastasis 7,16,17 .…”

Section: Introductionmentioning

confidence: 99%

Rational Identification of a Colorectal Cancer Targeting Peptide through Phage Display

Ferreira

Silva

Nóbrega

et al. 2019

Sci Rep

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Colorectal cancer is frequently diagnosed at an advanced stage due to the absence of early clinical indicators. Hence, the identification of new targeting molecules is crucial for an early detection and development of targeted therapies. This study aimed to identify and characterize novel peptides specific for the colorectal cancer cell line RKO using a phage-displayed peptide library. After four rounds of selection plus a negative step with normal colorectal cells, CCD-841-CoN, there was an obvious phage enrichment that specifically bound to RKO cells. Cell-based enzyme-linked immunosorbent assay (ELISA) was performed to assess the most specific peptides leading to the selection of the peptide sequence CPKSNNGVC. Through fluorescence microscopy and cytometry, the synthetic peptide RKOpep was shown to specifically bind to RKO cells, as well as to other human colorectal cancer cells including Caco-2, HCT 116 and HCT-15, but not to the normal non-cancer cells. Moreover, it was shown that RKOpep specifically targeted human colorectal cancer cell tissues. A bioinformatics analysis suggested that the RKOpep targets the monocarboxylate transporter 1, which has been implicated in colorectal cancer progression and prognosis, proven through gene knockdown approaches and shown by immunocytochemistry co-localization studies. The peptide herein identified can be a potential candidate for targeted therapies for colorectal cancer. Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide and the second leading cause of cancer-related deaths 1. The initiation and progression of benign adenoma to malignant adenocarcinoma may be driven by the accumulation of several gene mutations and epigenetic modifications 2. Early stage screening of CRC can potentially reduce both the incidence and mortality from this type of cancer. However, due to limitations of the current screening modalities in CRC (colonoscopy, biopsy and blood tests), several efforts are being conducted to discover new biomarkers that could be used as alternative screening tools for early diagnosis. Amongst these, peptide ligands that specifically recognize cell surface receptors are particularly promising and are being extensively used in cancer research. Peptides have become an attractive alternative, as they are easy to synthesize in large amounts and their smal size improves tissue penetration, with less nonspecific uptake by the reticuloendothelial system 3. Moreover, they can be chemically modified to alter affinity, charge, hydrophobicity, stability, and solubility and have been used to functionalize different nanosystems for improved and targeted therapy 4. Peptides can be selected in a relatively cost-effective manner using phage display 5-9. This powerful technology was first introduced in 1985 10 and has been modified to a rapid high-throughput one step method-Biopanning and Rapid Analysis of Selective Interactive Ligands (BRASIL) 11 , which has enabled the construction of a large number of phage peptide libraries, with a wide range of ap...

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“…If future research reveals that there is a very low quantity of endogenous NPCs that exist within the adult human SVZ, then biomaterial scaffolds designed to redirect endogenous NPCs are unlikely to promote neuronal repair on their own. Complementary strategies such as gene therapy or stem cell implants to rejuvenate the SVZ may be explored in parallel (189)(190)(191)(192)(193). Alternatively, future research may reveal that the human SVZ contains a sufficient quantity of NPCs to be redirected but that the RMS is non-existent or ineffective at eliciting neuronal migration within the adult brain.…”

Section: Challenges To Overcome and Potential Future Applicationsmentioning

confidence: 99%

Tissue Engineering and Biomaterial Strategies to Elicit Endogenous Neuronal Replacement in the Brain

et al. 2020

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Neurogenesis in the postnatal mammalian brain is known to occur in the dentate gyrus of the hippocampus and the subventricular zone. These neurogenic niches serve as endogenous sources of neural precursor cells that could potentially replace neurons that have been lost or damaged throughout the brain. As an example, manipulation of the subventricular zone to augment neurogenesis has become a popular strategy for attempting to replace neurons that have been lost due to acute brain injury or neurodegenerative disease. In this review article, we describe current experimental strategies to enhance the regenerative potential of endogenous neural precursor cell sources by enhancing cell proliferation in neurogenic regions and/or redirecting migration, including pharmacological, biomaterial, and tissue engineering strategies. In particular, we discuss a novel replacement strategy based on exogenously biofabricated "living scaffolds" that could enhance and redirect endogenous neuroblast migration from the subventricular zone to specified regions throughout the brain. This approach utilizes the first implantable, biomimetic tissue-engineered rostral migratory stream, thereby leveraging the brain's natural mechanism for sustained neuronal replacement by replicating the structure and function of the native rostral migratory stream. Across all these strategies, we discuss several challenges that need to be overcome to successfully harness endogenous neural precursor cells to promote nervous system repair and functional restoration. With further development, the diverse and innovative tissue engineering and biomaterial strategies explored in this review have the potential to facilitate functional neuronal replacement to mitigate neurological and psychiatric symptoms caused by injury, developmental disorders, or neurodegenerative disease.

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Novel subventricular zone early progenitor cell-specific adenovirus for in vivo therapy of central nervous system disorders reinforces brain stem cell heterogeneity

Cited by 8 publications

References 51 publications

Choroid Plexus: The Orchestrator of Long-Range Signalling Within the CNS

Choroid Plexus: The Orchestrator of Long-Range Signalling Within the CNS

Rational Identification of a Colorectal Cancer Targeting Peptide through Phage Display

Tissue Engineering and Biomaterial Strategies to Elicit Endogenous Neuronal Replacement in the Brain

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