Cyclic-RGD Peptides Increase the Adenoviral Transduction of Human Mesenchymal Stem Cells

King, William J.; Krebsbach, Paul H.

doi:10.1089/scd.2012.0379

Cited by 5 publications

(7 citation statements)

References 46 publications

(48 reference statements)

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“…Previous studies have demonstrated that, in the absence of protein coatings, RGD peptides presented on surfaces promote hMSC adhesion, proliferation, and viability, 76–78 and simply treating hMSCs with soluble RGD significantly increases adenoviral endocytosis and subsequent transgene expression. 79 Furthermore, fibroblast growth factor has been shown to promote proliferation, inhibit apoptosis, and reduce oxidative stress in hAMSCs, 80 and fibroblast growth factor-derived peptides have been conjugated to nucleic acid-complexing polymers 81 as well as viral vectors 82 to facilitate receptor-mediated endocytosis and subsequent transgene expression. Moreover, the cell penetrating R9 peptide on ECM mimetic substrates likely activates endocytic pathways in hMSCs to increase SMD transfection.…”

Section: Discussionmentioning

confidence: 99%

Screening a chemically defined extracellular matrix mimetic substrate library to identify substrates that enhance substrate-mediated transfection

Hamann

Thomas

Kozisek

et al. 2020

Exp Biol Med (Maywood)

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Nonviral gene delivery, though limited by inefficiency, has extensive utility in cell therapy, tissue engineering, and diagnostics. Substrate-mediated gene delivery (SMD) increases efficiency and allows transfection at a cell-biomaterial interface, by immobilizing and concentrating nucleic acid complexes on a surface. Efficient SMD generally requires substrates to be coated with serum or other protein coatings to mediate nucleic acid complex immobilization, as well as cell adhesion and growth; however, this strategy limits reproducibility and may be difficult to translate for clinical applications. As an alternative, we screened a chemically defined combinatorial library of 20 different extracellular matrix mimetic substrates containing combinations of (1) different sulfated polysaccharides that are essential extracellular matrix glycosaminoglycans (GAGs), with (2) mimetic peptides derived from adhesion proteins, growth factors, and cell-penetrating domains, for use as SMD coatings. We identified optimal substrates for DNA lipoplex and polyplex SMD transfection of fibroblasts and human mesenchymal stem cells. Optimal extracellular matrix mimetic substrates varied between cell type, donor source, and transfection reagent, but typically contained Heparin GAG and an adhesion peptide. Multiple substrates significantly increased transgene expression (i.e. 2- to 20-fold) over standard protein coatings. Considering previous research of similar ligands, we hypothesize extracellular matrix mimetic substrates modulate cell adhesion, proliferation, and survival, as well as plasmid internalization and trafficking. Our results demonstrate the utility of screening combinatorial extracellular matrix mimetic substrates for optimal SMD transfection towards application- and patient-specific technologies. Impact statement Substrate-mediated gene delivery (SMD) approaches have potential for modification of cells in applications where a cell-material interface exists. Conventional SMD uses ill-defined serum or protein coatings to facilitate immobilization of nucleic acid complexes, cell attachment, and subsequent transfection, which limits reproducibility and clinical utility. As an alternative, we screened a defined library of extracellular matrix mimetic substrates containing combinations of different glycosaminoglycans and bioactive peptides to identify optimal substrates for SMD transfection of fibroblasts and human mesenchymal stem cells. This strategy could be utilized to develop substrates for specific SMD applications in which variability exists between different cell types and patient samples.

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Section: Discussionmentioning

confidence: 99%

Screening a chemically defined extracellular matrix mimetic substrate library to identify substrates that enhance substrate-mediated transfection

Hamann

Thomas

Kozisek

et al. 2020

Exp Biol Med (Maywood)

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“…20 For instance, a recent study showed that cRGD significantly increased the affinity for v3 integrin when compared to its linear counterpart. 21…”

Section: Discussionmentioning

confidence: 99%

“…20 For instance, a recent study showed that cRGD significantly increased the affinity for v3 integrin when compared to its linear counterpart. 21 Importantly, modification of the peptide backbone requires unfolding of the nanoscale bioactive molecular aggregations in order to fully permit their respective functions while simultaneously preventing any compromise of stability of the SAP structure in a physiological environment. Considering bioactive peptide motifs can conjugate RADA 16 at the C-terminus, 16 a recent study has optimized the linkage approach of motif peptides with the backbone sequence.…”

Section: Functional Motif-enhanced Sapnh Forms a Designer 3d Ecm For mentioning

confidence: 99%

Functionalized self-assembly polypeptide hydrogel scaffold applied in modulation of neural progenitor cell behavior

Gao

Tao

Wang

et al. 2016

Journal of Bioactive and Compatible Polymers

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Three-dimensional cell culturing provides an appealing biomimetic platform to probe the biological effects of a designed extracellular matrix on the behavior of seeded neural stem or neural progenitor cells. This culturing model serves as an important tool to investigate functional regulators involved in proliferation and differentiation of neural progenitor cells. This study aims to reconstruct a polypeptide hydrogel matrix functionally integrated with cyclo-RGD motif [c(RGDfK)] for initial exploration of neural progenitor cell behavior in three-dimensional culture. Three types of hydrogel scaffolds including Type I collagen, RADA16 self-assembly peptide, and RADA16-c(RGDfK) self-assembly peptide hydrogel were employed to serve as the culturing extracellular matrix of neonatal rat spinal neural progenitor cells. The neural adhesion of functionalized self-assembly peptide hydrogel was acquired prior to its RADA16 counterpart with neural progenitor cell seeding tests. The biophysiological properties of self-assembly peptide hydrogel scaffolds were then detected by scanning electron microscopy and rheology measurements. The biological behavior of embedded neural progenitor cells including cell proliferation and differentiation in three-dimensional niche were analyzed by MTT [(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)] tests and immunocytochemistry fluorescence staining. The 1% (w/v) RADA16-c(RGDfK) hydrogel scaffold [R16-c(RGDfK)HS] demonstrated an elastic modulus(312 ± 5.7 Pa) compatible with central neural cells, which significantly facilitated the proliferation of embedded neural progenitor cells. Compared to collagen hydrogel, both RADA16 and RADA16-c(RGDfK) hydrogel scaffold improved the cellular proliferation and neuronal differentiation of neural progenitor cells in a three-dimensional culture model. In order to model neuronal regeneration, introduction of neurotrophin-3 in the differentiation environment significantly increased the neuronal differentiation in which the ratio of Tuj-1-positive cell number increased to 72.5% ± 4.7% in the c(RGDfK)-functionalized three-dimensional matrix environment at 7 days in culture. Collectively, the present R16-c(RGDfK)HS displays excellent central neural biocompatibility and emerges as a promising bioengineered extracellular matrix niche of neural stem or progenitor cells, building a solid foundation for the subsequent in vitro and in vivo studies including neural repair, regeneration, and development.

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“…Cyclic-RGD peptides can be used to improve the transduction efficacy of Ad vectors in vitro . Human mesenchymal stem cells can be efficiently transduced by using a GFP-expressing Ad vector in presence of cyclic-RGD peptides [ 125 ].…”

Section: Re-targeting Of Ad Vectorsmentioning

confidence: 99%

The Evolution of Adenoviral Vectors through Genetic and Chemical Surface Modifications

Capasso

Garofalo

Hirvinen

et al. 2014

Viruses

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A long time has passed since the first clinical trial with adenoviral (Ad) vectors. Despite being very promising, Ad vectors soon revealed their limitations in human clinical trials. The pre-existing immunity, the marked liver tropism and the high toxicity of first generation Ad (FG-Ad) vectors have been the main challenges for the development of new approaches. Significant effort toward the development of genetically and chemically modified adenoviral vectors has enabled researchers to create more sophisticated vectors for gene therapy, with an improved safety profile and a higher transduction ability of different tissues. In this review, we will describe the latest findings in the high-speed, evolving field of genetic and chemical modifications of adenoviral vectors, a field in which different disciplines, such as biomaterial research, virology and immunology, co-operate synergistically to create better gene therapy tools for modern challenges.

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Cyclic-RGD Peptides Increase the Adenoviral Transduction of Human Mesenchymal Stem Cells

Cited by 5 publications

References 46 publications

Screening a chemically defined extracellular matrix mimetic substrate library to identify substrates that enhance substrate-mediated transfection

Screening a chemically defined extracellular matrix mimetic substrate library to identify substrates that enhance substrate-mediated transfection

Functionalized self-assembly polypeptide hydrogel scaffold applied in modulation of neural progenitor cell behavior

The Evolution of Adenoviral Vectors through Genetic and Chemical Surface Modifications

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