Lentiviral gene therapy vectors encoding VIP suppressed diabetes-related inflammation and augmented pancreatic beta-cell proliferation

Erendor, Fulya; Şahin, Elif; Şanlioğlu, Ahter Dilşad; Balcı, Mustafa Kemal; Griffith, Thomas S.; Şanlıoğlu, Salih

doi:10.1038/s41434-020-0183-3

Cited by 12 publications

(12 citation statements)

References 62 publications

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“…Recently, the therapeutic efficacy of lentivirus‐mediated VIP gene delivery was explored in mouse models of both Type 1 and Type 2 diabetes mellitus. LentiVIP delivery not only enhanced insulin sensitivity and glucose tolerance in diet‐induced obese Type 2 models (Tasyurek et al, 2018), but also improved glucose tolerance, reduced hyperglycemia, and prevented weight loss in streptozotocin‐induced Type 1 diabetic models (Erendor et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Microglia cells treated with synthetic vasoactive intestinal peptide or transduced with LentiVIP protect neuronal cells against degeneration

Goksu,

Kocanci,

Akinci

et al. 2024

Eur J of Neuroscience

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A common pathological hallmark of neurodegenerative disorders is neuronal cell death, accompanied by neuroinflammation and oxidative stress. The vasoactive intestinal peptide (VIP) is a pleiotropic peptide that combines neuroprotective and immunomodulatory actions. The gene therapy field shows long‐term promise for treating a wide range of neurodegenerative diseases (ND). In this study, we aimed to investigate the in vitro efficacy of transduction of microglia using lentiviral gene therapy vectors encoding VIP (LentiVIP). Additionally, we tested the protective effects of the secretome derived from LentiVIP‐infected “immortalized human” microglia HMC3 cells, and cells treated with Synthetic VIP (SynVIP), against toxin‐induced neurodegeneration. First, LentiVIP, which stably expresses VIP, was generated and purified. VIP secretion in microglial conditioned media (MG CM) for LentiVIP‐infected HMC3 microglia cells was confirmed. Microglia cells were activated with lipopolysaccharide, and groups were formed as follows: 1) Control, 2) SynVIP‐treated, or 3) LentiVIP‐transduced. These MG CM were applied on an in vitro neurodegenerative model formed by differentiated (d)‐SH‐SY5Y cells. Then, cell survival analysis and apoptotic nuclear staining, besides measurement of oxidative/inflammatory parameters in CM of cells were performed. Activated MG CM reduced survival rates of both control and toxin‐applied (d)‐SH‐SY5Y cells, whereas LentiVIP‐infected MG CM and SynVIP‐treated ones exhibited better survival rates. These findings were supported by apoptotic nuclear evaluations of (d)‐SH‐SY5Y cells, alongside oxidative/inflammatory parameters in their CM. LentiVIP seems worthy of further studies for the treatment of ND because of the potential of gene therapy to treat diseases effectively with a single injection.

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Section: Discussionmentioning

confidence: 99%

Microglia cells treated with synthetic vasoactive intestinal peptide or transduced with LentiVIP protect neuronal cells against degeneration

Goksu,

Kocanci,

Akinci

et al. 2024

Eur J of Neuroscience

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“…VIP effects were found on immune and inflammatory responses by promoting T helper cell differentiation, stimulating regulatory T cell synthesis, and downregulating macrophage action [ 34 ]. VIP was also shown to inhibit proinflammatory cytokine release (such as IL-6, TNF-α, IL-12) and increase IL-10 synthesis [ 34 , 48 ]. Additionally, VIP exerts its anti-inflammatory effect by regulation of the epithelial barrier function, mainly by increasing the secretion of ions and fluids in the intestines and control of epithelial tight junction proteins synthesis [ 34 , 49 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of Acrylamide Supplementation on the Population of Vasoactive Intestinal Peptide (VIP)-Like Immunoreactive Neurons in the Porcine Small Intestine

Palus¹,

Bulc²,

Całka³

2020

IJMS

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Acrylamide is one of the harmful substances present in food. The present study aimed to establish the effect of acrylamide supplementation in tolerable daily intake (TDI) dose (0.5 µg/kg b.w./day) and a dose ten times higher than TDI (5 µg/kg b.w./day) on the population of vasoactive intestinal peptide-like immunoreactive (VIP-LI) neurons in the porcine small intestine and the degree of the co-localization of VIP with other neuroactive substances (neuronal nitric oxide synthase (nNOS), substance P (SP), and cocaine- and amphetamine-regulated transcript peptide (CART)). In our work, 15 Danish landrace gilts (5 in each experimental group) received capsules (empty or with low or high doses of acrylamide) for a period of 28 days with their morning feeding. Using double immunofluorescence staining, we established that acrylamide supplementation increased the number of neurons showing immunoreactivity towards VIP in all types of enteric nervous system (ENS) plexuses and fragments of the small intestine studied. Moreover, both doses of acrylamide led to changes in the degree of co-localization of VIP with nNOS, SP, and CART in intramural neurons. The observed changes may be the adaptation of neurons to local inflammation, oxidative stress, or the direct toxic effects of acrylamide on intestinal neurons, also referred to as neuronal plasticity.

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“…These three approaches are stimulation of the proliferation of existing beta cells, reprogramming various types of cells into beta cells, and inducing differentiation of beta cells from PSCs. Pancreatic islet-cell proliferation can also be induced in vivo using gene therapy approaches as shown previously[ 71 - 73 ]. In this context of utilizing pluripotent stem cells, pancreatic beta cell-like insulin-producing cells (IPCs) differentiated from ESCs, which were first isolated from human embryos in 1989; and iPSCs, which were first obtained by reprogramming of differentiated cells, have created excitement as new potential sources of beta cells[ 74 - 76 ].…”

Section: The Role Of Programmable Nucleases In Pancreatic Beta-cell Development and Functionmentioning

confidence: 95%

Genome engineering and disease modeling via programmable nucleases for insulin gene therapy; promises of CRISPR/Cas9 technology

Eksi¹,

Şanlioğlu²,

Akkaya³

et al. 2021

WJSC

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Targeted genome editing is a continually evolving technology employing programmable nucleases to specifically change, insert, or remove a genomic sequence of interest. These advanced molecular tools include meganucleases, zinc finger nucleases, transcription activator-like effector nucleases and RNA-guided engineered nucleases (RGENs), which create double-strand breaks at specific target sites in the genome, and repair DNA either by homologous recombination in the presence of donor DNA or via the error-prone non-homologous end-joining mechanism. A recently discovered group of RGENs known as CRISPR/Cas9 gene-editing systems allowed precise genome manipulation revealing a causal association between disease genotype and phenotype, without the need for the reengineering of the specific enzyme when targeting different sequences. CRISPR/Cas9 has been successfully employed as an ex vivo gene-editing tool in embryonic stem cells and patient-derived stem cells to understand pancreatic beta-cell development and function. RNA-guided nucleases also open the way for the generation of novel animal models for diabetes and allow testing the efficiency of various therapeutic approaches in diabetes, as summarized and exemplified in this manuscript.

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Lentiviral gene therapy vectors encoding VIP suppressed diabetes-related inflammation and augmented pancreatic beta-cell proliferation

Cited by 12 publications

References 62 publications

Microglia cells treated with synthetic vasoactive intestinal peptide or transduced with LentiVIP protect neuronal cells against degeneration

Microglia cells treated with synthetic vasoactive intestinal peptide or transduced with LentiVIP protect neuronal cells against degeneration

Effect of Acrylamide Supplementation on the Population of Vasoactive Intestinal Peptide (VIP)-Like Immunoreactive Neurons in the Porcine Small Intestine

Genome engineering and disease modeling via programmable nucleases for insulin gene therapy; promises of CRISPR/Cas9 technology

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