Needle injection catheter delivery of the gene for an antibacterial agent inhibits neointimal formation

Nikol, Sigrid; Huehns, Tanya Y.; Krausz, Eberhard; Armeanu, Sorin; Engelmann, Markus G.; Winder, David M.; Salmons, Brian; Hoefling, Berthold

doi:10.1038/sj.gt.3300888

Cited by 41 publications

(74 citation statements)

References 38 publications

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“…Defensins may turn out to be antibacterial agents with low susceptibility to resistance mechanisms, and thus gene therapy using these or the related genes is of great potential for treating intractable infectious diseases. [9][10][11] As mentioned above, HBD3 is salt-insensitive and is effective for Gram-positive bacteria, which are common cause of the skin infection. In this study, we introduced the HBD3 gene into a keratinocyte cell line and prepared the epidermal graft overexpressing HBD3 to determine the usefulness or feasibility of HBD3 engineered epidermis as a novel antibacterial therapy.…”

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confidence: 99%

Beta defensin-3 engineered epidermis shows highly protective effect for bacterial infection

et al. 2005

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Defensins are small cationic proteins that harbor broadspectrum microbicidal activity against bacteria, fungi and viruses. This study examines the effects on pathogens of the epidermis engineered to express human beta-defensin 3 (HBD3) to combat bacterial infections. First, we examined the localization of HBD3 in the epidermis and observed HBD3 in the intercellular spaces and lamellar bodies of the upper epidermal layers. This result showed HBD3 expressed and assembled in the outer layers of the epidermis was suspected to counter the invading microorganisms. Next, we established a keratinocyte cell line that stably expressed HBD3 and found that the culture medium showed antibacterial activity. Furthermore, we prepared an epidermal sheet of these cells with the HBD3 gene and grafted this onto a dermal wound on a nude rat. The HBD3 engineered epidermis demonstrated significant antimicrobial activity. Skin ulcers without epidermis are constantly exposed to invading microorganisms. Biopsy samples of re-epithelizing epidermis from patients with skin ulcers were collected, and HBD3 mRNA level measured in the epidermis. The epidermal samples from the ulcer skin expressed 2.5 times higher levels of HBD3 transcript than those in the control skin. These results, taken together, indicate that the therapeutic introduction of the HBD3 gene into somatic cells may provide a new gene therapy strategy for intractable infectious diseases. Gene Therapy (2005) 12, 857-861.

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Beta defensin-3 engineered epidermis shows highly protective effect for bacterial infection

et al. 2005

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“…The outgrowing SMCs were tested by immuno-histochemistry for α-actin expression. 12 SMCs were cultured in a growth medium (HAM'S F-12 : Waymouth = 1:1;…”

Section: Cell Culturesmentioning

confidence: 99%

“…14,17,18 Treated vessels were explanted 3 months after treatment and analyzed as described. 2,[12][13][14][15]17,18 Transferred Plasmid DNA Analysis…”

Section: Balloon-injured Porcine Peripheral Artery Gene Transfer In Vivomentioning

confidence: 99%

“…ACC 310) from the umbilical cord vein, primary porcine SMCs, and ECs were used and cultivated as described previously. [12][13][14] In Vitro Gene Transfer Vascular cells were transfected with either DOCSPER 11 or linear polyethylenimine (PEI22) as described previously. [12][13][14][15] mRNA Analysis of the Transfected Genes and NP…”

Section: Cell Culturesmentioning

confidence: 99%

“…14,17,18 Treated vessels were explanted 3 months after treatment and analyzed as described. 2,[12][13][14][15]17,18 Transferred Plasmid DNA AnalysisPlasmid DNA was detected by PCR amplifying a partial sequence of the plasmids used: pCMV␤-L/pCMV␤-R (647 bp), pTrCMV2-L/ CNP-R3 (460 bp), and GAPDH-L2/GAPDH-R (550 bp; Table). All PCR reactions were performed using the following conditions: 45 s 94°C, 1 minute 60°C, and 45 s at 72°C for 35 cycles.…”

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Functional Analysis of Genomic DNA, cDNA, and Nucleotide Sequence of the Mature C-Type Natriuretic Peptide Gene in Vascular Cells

Pelisek

Kuehnl²,

Rolland³

et al. 2004

ATVB

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Objective-The aim of this study was to investigate the effect of various C-type natriuretic peptide (CNP) sequences (genomic DNA [CNPDNA], cDNA derived from mRNA [CNPcDNA], and sequence coding for 22 amino acids of the mature CNP [CNP22aa]) on the growth of primary porcine vascular cells. Methods and Results-Gene transfer was performed with cationic lipid DOCSPER or linear polyethylenimine. All 3 CNP sequences led to significant inhibition of smooth muscle cell (SMC) proliferation. In contrast, significant stimulation of cell growth was observed in endothelial cells (ECs) using CNPDNA or CNPcDNA but not CNP22aa. In a porcine restenosis model, a significant reduction in neointima hyperplasia was found 3 months after application of the CNPcDNA vector compared with the control transfection. Conclusions-The results demonstrate that the first intron in the CNP sequence does not contain any additional enhancerbinding sites. However, the signal sequence is indispensable for secretion of CNP and its appropriate physiological function. Key Words: C-type natriuretic peptide Ⅲ vascular cells Ⅲ gene transfer Ⅲ proliferation Ⅲ restenosis C -type natriuretic peptide (CNP) is a promising therapeutic agent for prevention of restenosis after angioplasty. 1-3 CNP inhibits smooth muscle cell (SMC) proliferation, decreases extracellular matrix synthesis, promotes revascularization, and positively influences vascular remodeling. 2,3 The CNP gene has been localized to chromosome 2 in the human genome, and its sequence is the most highly conserved of the natriuretic peptides across many species. 4,5 Sequence analysis reveals that there are a total of 3 exons and 2 introns. In the coding region for prepro CNP, the first 2 exons are separated by an intron. 6 Exon 3, coding for poly A, is removed during the processing pathway within the nucleus. The gene is flanked in the 5Ј-region by cis-acting regulatory elements that are not part of the other natriuretic peptide genes, suggesting that the regulation mechanisms for CNP gene transcription are different compared with the other natriuretic peptides. 6 The function of the first intron regarding transcription regulation of this gene is so far unknown. However, a number of genes are known to be regulated by enhancer elements outside the coding region, and many of them contain regulatory sequences within the first intron. 7,8 The CNP gene encodes a 126-residue precursor peptide that is processed to generate 22-and 53-aa peptides (human CNP22 and human CNP53, respectively). 9 CNP22 is more widely and abundantly expressed and is more potent than CNP53. 5,9 The amino terminal of prepro CNP contains a signal peptide sequence that allows the synthesized peptide to pass from the endoplasmic reticulum to the Golgi complex, where it is packed into granules from which CNP is then released at the cell surface by exocytosis. The signal peptide sequence is generally necessary for protein secretion. However, some proteins, such as fibroblast growth factor-2 (FGF-2), are secreted into the extracellular med...

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Minimally Invasive and Regenerative Therapeutics

et al. 2018

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Advances in biomaterial synthesis and fabrication, stem cell biology, bioimaging, microsurgery procedures, and microscale technologies have made minimally invasive therapeutics a viable tool in regenerative medicine. Therapeutics, herein defined as cells, biomaterials, biomolecules, and their combinations, can be delivered in a minimally invasive way to regenerate different tissues in the body, such as bone, cartilage, pancreas, cardiac, skeletal muscle, liver, skin, and neural tissues. Sophisticated methods of tracking, sensing, and stimulation of therapeutics in vivo using nanobiomaterials and soft bioelectronic devices provide great opportunities to further develop minimally invasive and regenerative therapeutics (MIRET). In general, minimally invasive delivery methods offer high yield with low risk of complications and reduced costs compared to conventional delivery methods. Here, we review minimally invasive approaches for delivering regenerative therapeutics into the body. The use of MIRET to treat different tissues and organs is described. Although some clinical trials have been done using MIRET, it is hoped that such therapeutics find wider applications to treat patients. Finally, we highlight some future perspective and challenges for this emerging field.

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Needle injection catheter delivery of the gene for an antibacterial agent inhibits neointimal formation

Cited by 41 publications

References 38 publications

Beta defensin-3 engineered epidermis shows highly protective effect for bacterial infection

Beta defensin-3 engineered epidermis shows highly protective effect for bacterial infection

Functional Analysis of Genomic DNA, cDNA, and Nucleotide Sequence of the Mature C-Type Natriuretic Peptide Gene in Vascular Cells

Minimally Invasive and Regenerative Therapeutics

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