Cerebrum Repair with PHPMA Hydrogel Immobilized with Neurite-Promoting                Peptides in Traumatic Brain Injury of Adult Rat Model

Cui, Fuzhai; Tian, Weiming; Fan, Yuwei; Hou, Shaoping; Xu, Qunyuan; Lee, I.-S.

doi:10.1177/0883911503040470

Cited by 15 publications

(11 citation statements)

References 36 publications

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“…In previous studies, IKVAV‐modified hydrogels have been proven to promote adhesion, growth and proliferation of neural stem cells , and neuron adhesion, growth and proliferation in vitro . In implantation assays, IKVAV peptide‐grafted scaffolds have been shown to enhance regenerative function of brain and spinal cord cells.…”

Section: Discussionmentioning

confidence: 99%

IKVAV regulates ERK1/2 and Akt signalling pathways in BMMSC population growth and proliferation

Qiu

Zhang

et al. 2014

Cell Proliferation

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ObjectivesThe molecular mechanism of bone marrow mesenchymal stem cell (BMMSC) population growth and proliferation, induced by Isoleucyl-lysyl-valyl-alanyl-valine (IKVAV), was explored in this study.Materials and methodsIKVAV peptides were synthesized by the solid-phase method. Influence of IKVAV on BMMSC population growth and proliferation were investigated by assays of CCK-8, flow cytometry, real-time PCR and western blotting.ResultsIKVAV peptide was found to induce proliferation and proliferating cell nuclear antigen (PCNA) synthesis of BMMSC in a dose- and time-dependent manner. Cell cycle analysis showed that the proportion of IKVAV-treated BMMSC in S phase in was higher than controls. Western blot results suggested that mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signalling pathways were activated by IKVAV by enhancing phosphorylation levels of ERK1/2 and Akt in the BMMSCs. Meanwhile, phosphorylation levels of ERK1/2 and Akt were partially blocked by ERK1/2 inhibitor (PD98059) and Akt inhibitor (wortmannin), respectively.ConclusionsOur results demonstrated that IKVAV stimulated BMMSC population growth and proliferation by activating MAPK/ERK1/2 and PI3K/Akt signalling pathways. This study is the first to reveal an enhancement effect of IKVAV peptide on BMMSC at the signal transduction level, and the outcome could provide experimental evidence for application of IKVAV-grafted scaffolds in the field of BMMSC-based tissue engineering.

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Section: Discussionmentioning

confidence: 99%

IKVAV regulates ERK1/2 and Akt signalling pathways in BMMSC population growth and proliferation

Qiu

Zhang

et al. 2014

Cell Proliferation

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“…NF160‐positive axons respond similarly to pHPMA and pHEMA hydrogels implanted into the brain of rats however there was a greater amount of connective tissue growth into the pHPMA hydrogel compared to the pHEMA 142. Immobilisation of the xIKVAVx (isoleucine‐lysine‐valine‐alanine‐valine) peptide on pHPMA hydrogels provided structural continuity across cavities made in the adult rat cerebrum, resulting in a more favourable wound repair and subsequently axonal growth throughout the hydrogel 135. RGD has also been immobilised on pHPMA143 but with the intention of promoting fibroblast growth.…”

Section: Synthetic Hydrogelsmentioning

confidence: 99%

“…Poly(hydroxypropyl methacrylate) (pHPMA) is more biocompatible than pHEMA131 and shows great promise in aiding regeneration following lesions of the CNS 120, 132, 133. pHPMA hydrogels are often used with other molecules, such as attached adhesive peptides 134, 135. They have a colloidal‐type structure with microspheres 3–5 μm in diameter in a loosely packed structure forming a three‐dimensional network 131.…”

Section: Synthetic Hydrogelsmentioning

confidence: 99%

Neural tissue engineering of the CNS using hydrogels

Nisbet¹,

Crompton²,

Horne³

et al. 2007

J Biomed Mater Res

156

125

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Current therapies have limited capacity to curtail disease progression or damage of the central nervous system (CNS) of adult mammals and successful regeneration following injury or disease does not occur. Regeneration of the CNS is limited by physical and chemical inhibitory barriers within the injured environment and the absence of positive cues that elicit and guide repair. Neural tissue engineering strategies focus on developing scaffolds that artificially generate favourable cellular microenvironments that attempt to tip the balance in favour of regeneration. Some recent advances using scaffolds to promote regeneration within the CNS, particularly in conjunction with stem cells, has generated promising results. This review focuses on hydrogel scaffolds which have been used extensively in neural tissue engineering applications and addresses the physical and chemical modifications of these materials to promote nerve regeneration.

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“…Myriad biomaterials, including collagen, 6 polycarbonate, 7 polylactide and poly(N-(2-hydroxylpropyl) methacrylamide) (PHPMA) hydrogels, 8 and modified hyaluronic acid hydrogels. 9 have been used as implants in experimental brain lesions in animal models with variable results.…”

Section: Introductionmentioning

confidence: 99%

Non-Viral Delivery of the Gene for Glial Cell Line-Derived Neurotrophic Factor to Mesenchymal Stem Cells In Vitro Via a Collagen Scaffold

Bolliet

Bohn

Spector

2008

Tissue Engineering Part C: Methods

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Recent advances in tissue engineering that combine an extracellular matrix-like scaffold with therapeutic molecules, cells, DNA encoding therapeutic proteins, or a combination of the three hold promise for treating defects in the brain resulting from a penetrating injury or tumor resection. The purpose of this study was to investigate a porous sponge-like collagen scaffold for non-viral delivery of a plasmid encoding for glial cell line-derived neurotrophic factor (pGDNF) to rat marrow stromal stem cells (also referred to as mesenchymal stem cells, MSCs). The effects of the following parameters on GDNF synthesis in the three-dimensional (3D) constructs were evaluated and compared with results in monolayer culture: initial plasmid load (2-50 microg pGDNF), ratio of a lipid transfection reagent to plasmid (5:10), culture environment during the transfection (static and dynamic), and cell density. The level of gene expression in the collagen scaffolds achieved therapeutic levels that had previously been found to support survival of dopaminergic and trigeminal neurons in vitro. For the highest loading of plasmid (50 microg), the level of GDNF protein remained six to seven times above the control level after 2 weeks, a significant difference. Cell density in the scaffold was of importance for an early increase in GDNF production, with accumulated GDNF being approximately 60% greater after 9 days of culture when scaffolds were initially seeded with 2 million rat MSCs compared to 500,000 cells. Application of orbital shaking during the 4 h of transfection had a positive effect on the production of GDNF on 3D constructs but not of the same magnitude as reported in monolayer studies. Overall, these results demonstrate that the combination of tissue engineering and non-viral transfection of MSCs for the over-expression of GDNF is a promising approach for the long-term production of GDNF and probably for neurotrophic factors in general.

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Cerebrum Repair with PHPMA Hydrogel Immobilized with Neurite-Promoting Peptides in Traumatic Brain Injury of Adult Rat Model

Cited by 15 publications

References 36 publications

IKVAV regulates ERK1/2 and Akt signalling pathways in BMMSC population growth and proliferation

IKVAV regulates ERK1/2 and Akt signalling pathways in BMMSC population growth and proliferation

Neural tissue engineering of the CNS using hydrogels

Non-Viral Delivery of the Gene for Glial Cell Line-Derived Neurotrophic Factor to Mesenchymal Stem Cells In Vitro Via a Collagen Scaffold

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