Neural Stem Cells Modified by a Hypoxia-Inducible VEGF Gene Expression System Improve Cell Viability under Hypoxic Conditions and Spinal Cord Injury

Hong, Jin; Pennant, William A.; Lee, Min Hyung; Cha, Sungsu; Kim, Hyun Ah; Liu, Meng Lu; Oh, Jin Soo; Cho, Joon; Kh, Kim; Yoon, Do Heum; Ha, Yoon

doi:10.1097/brs.0b013e3181e7f34b

Cited by 21 publications

(12 citation statements)

References 33 publications

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“…Consequently, additional administration of one of these factors can be applied as an alternative strategy to expensive hypoxic preconditioning. While erythropoietin already demonstrated a beneficial effect on the survival of different kinds of progenitor cells after transplantation [122-124], HIF-1α-transduced MSCs significantly improved myocardial infarction [125] and VEGF-overexpressing neural stem cells demonstrated higher cell survival in an injured spinal cord [126]. Attention needs to be paid to additional genetic or phenotypic alterations that might be introduced accidentally upon modification of MSCs in order to produce hypoxia-resistant cells.…”

Section: Introductionmentioning

confidence: 99%

Tackling the physiological barriers for successful mesenchymal stem cell transplantation into the central nervous system

et al. 2013

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Over the past decade a lot of research has been performed towards the therapeutic use of mesenchymal stem cells (MSCs) in neurodegenerative and neuroinflammatory diseases. MSCs have shown to be beneficial in different preclinical studies of central nervous system (CNS) disorders due to their immunomodulatory properties and their capacity to secrete various growth factors. Nevertheless, most of the transplanted cells die within the first hours after transplantation and induce a neuroinflammatory response. In order to increase the efficacy of MSC transplantation, it is thus imperative to completely characterise the mechanisms mediating neuroinflammation and cell death following MSC transplantation into the CNS. Consequently, different components of these cell death- and neuroinflammation-inducing pathways can be targeted in an attempt to improve the therapeutic potential of MSCs for CNS disorders.

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Section: Introductionmentioning

confidence: 99%

Tackling the physiological barriers for successful mesenchymal stem cell transplantation into the central nervous system

et al. 2013

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“…As early as in 2000, it was reported that VEGF and VEGF receptors in the spinal cord was induced after mechanical spinal injury and prostaglandin administration [17]. Later on, increases in VEGF-A have been shown to be beneficial for post-SCI recovery in most of the studies [18-21], although ineffective results have also been shown [22]. Nevertheless, adverse effects of VEGF-A have not been reported.…”

Section: Discussionmentioning

confidence: 96%

Comprehensive Effects of Suppression of MicroRNA-383 in Human Bone-Marrow-Derived Mesenchymal Stem Cells on Treating Spinal Cord Injury

Wei

Zheng

An³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Transplantation of bone-marrow-derived mesenchymal stem cells (MSCs) promotes neural cell regeneration after spinal cord injury (SCI). Recently, we showed that suppression of microRNA-383 (miR-383) in MSCs increased the protein levels of glial cell line derived neurotrophic factor (GDNF), resulting in improved therapeutic effects on SCI. However, the overall effects of miR-383 suppression in MSCs on SCI therapy were not determined yet. Here, we addressed this question. Methods: We used bioinformatics tools to predict all miR-383-targeting genes, confirmed the functional bindings in a dual luciferase reporter assay. The effects of alteration of candidate genes in MSCs on cell proliferation were analyzed by MTT assay and by Western blotting for PCNA. The effects on angiogenesis were assessed by HUVEC assay. The effects on SCI in vivo were analyzed by transplantation of the modified MSCs into nude rats that underwent SCI. Results: Suppression of miR-383 in MSCs not only upregulated GDNF protein, but also increased vascular endothelial growth factor A (VEGF-A) and cyclin-dependent kinase 19 (CDK19), two other miR-383 targets. MiR-383-suppression-induced increases in CDK19 resulted in a slight but significant increase in MSC proliferation, while miR-383-suppression-induced increases in VEGF-A resulted in a slight but significant increase in MSC-mediated angiogenesis. Conclusions: Upregulation of CDK19 and VEGF-A by miR-383 suppression in MSCs further improve the therapeutic potential of MSCs in treating SCI in rats.

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“…Because NSCs have the potential to differentiate into neurons (Lee et al, 2012), oligodendrocytes, and axons (Decimo et al, 2011;Yasuda et al, 2011) and also have the ability to fill the spinal cord cavity and blend with host spinal cord tissues (Boido et al, 2011;Li et al, 2011), they may be useful for repairing SCI. Animal experiments have indicated that the regenerated axon has limited ability to cross fiber scars to set up new neural pathways because the internal environment of the organism affects the survival and differentiation of NSCs (Lian Jin et al, 2011;Meng et al, 2011;Su et al, 2011;Wang et al, 2011;Wakai et al, 2014). Therefore, limited effects would be observed for the repair using only NSCs.…”

Section: Discussionmentioning

confidence: 99%

Effectiveness of muscle basal lamina carrying neural stem cells and olfactory ensheathing cells in spinal cord repair

et al. 2015

Genet. Mol. Res.

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ABSTRACT.We examined the effect of muscle basal lamina (MBL) with neural stem cells (NSCs) and olfactory ensheathing cells (OECs) on spinal cord injury repair. Seventy-two Sprague-Dawley rats were subjected to spinal cord hemisection and divided into 6 groups. In blank control group (group A), the ends of the spinal cord hemisection model were flushed with physiological saline. In NSC transplantation group (B), OEC transplantation group (C), MBL with NSC transplantation group (D), MBL with OEC transplantation group (E), and MBL with NSC and OEC transplantation group (F), NSCs, OECs, MBL with NSCs, MBL with OECs, and MBL with NSCs and OECs were implanted into the ends of the hemisection model. Survival and migration of transplanted cells were detected by immunohistochemistry and immunofluorescence after 4 and 8 weeks. Hind limb function repair was evaluated by Bundle branch block score at various time points before and after surgery. MBL could promote NSC growth along its lumen and promote host cell advancement in the lumen, reducing local inflammatory responses. Using MBL with NSCs 13438 X.W. Kang et al.©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (4): 13437-13455 (2015) and/or OECs for spinal cord repair shows advantages over simple cell transplantation. Group F contained more nerve cells in muscle basal lamina than group E. This method is useful for forming more axons, synaptic connections, and signal transduction pathways. However, these new axons showed nerve demyelination, which may greatly limit nerve signal conduction. In group F, OECs could induce neural stem cells, axonal growth, and synaptic connection formation, but its role is limited.

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Neural Stem Cells Modified by a Hypoxia-Inducible VEGF Gene Expression System Improve Cell Viability under Hypoxic Conditions and Spinal Cord Injury

Abstract: These results strongly suggest the potential utility of mNSCs modified by a hypoxia-inducible VEGF gene expression system in the development of effective stem cell transplantation protocols in SCI.

Cited by 21 publications

References 33 publications

Tackling the physiological barriers for successful mesenchymal stem cell transplantation into the central nervous system

Tackling the physiological barriers for successful mesenchymal stem cell transplantation into the central nervous system

Comprehensive Effects of Suppression of MicroRNA-383 in Human Bone-Marrow-Derived Mesenchymal Stem Cells on Treating Spinal Cord Injury

Effectiveness of muscle basal lamina carrying neural stem cells and olfactory ensheathing cells in spinal cord repair

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