Replication defective adenoviral vectors have been demonstrated as an effective method for delivering genes into a variety of cell types and tissues both in vivo and in vitro. Transfecting genes into neuronal cells has proven to be difficult because of their lack of cell division. Since the major problem in neurological disease is the degeneration of the terminally differentiated neuronal cells, the adenoviral vector's ability to transfer genes into differentiated post-mitotic cells makes them advantageous for a gene delivery system for the nervous system. Here we showed that a replication defective recombinant adenovirus carrying the lacZ gene could infect the neuronal stem cells and even the differentiated neuronal cells derived from the central nervous system. The lacZ gene delivered into the neuronal cells was expressed efficiently. In addition, the recombinant virus also infected Schwann cells in intact and injured nerves in vivo. The expression of the lacZ gene lasted for 5 weeks, within which nerve regeneration is accomplished in the rat. Adenoviral vectors might thus be used to modulate Schwann cell gene expression for treating peripheral nerve injury or peripheral neuropathy.
"During Wallerian degeneration, a process of gradual nerve degeneration in the distal stump of the injury site when the peripheral nervous system (PNS) is injured, axons and myelin sheaths are degenerated and removed for regrowing axons. When axons outgrow from the nerve ending sites toward the distal stump at the site of injury, Schwann cells remyelinate the new axons [14, 15]. Enhancing the axonal regrowth by any small compounds, it can be therapeutic for improving PNS nerve regeneration. "
[Show abstract][Hide abstract] ABSTRACT: Aucubin is an iridoid glycoside with a wide range of biological activities, including anti-inflammatory, anti-microbial, anti-algesic as well as anti-tumor activities. Recently, it has been shown that aucubin prevents neuronal death in the hippocampal CA1 region in rats with diabetic encephalopathy. In addition, it has protective effects on H2O2-induced apoptosis in PC12 cells. We have shown here that aucubin promotes neuronal differentiation and neurite outgrowth in neural stem cells cultured primarily from the rat embryonic hippocampus. We also investigated whether aucubin facilitates axonal elongation in the injured peripheral nervous system. Aucubin promoted lengthening and thickness of axons and re-myelination at 3 weeks after sciatic nerve injury. These results indicate that administration of aucubin improved nerve regeneration in the rat model of sciatic nerve injury, suggesting that aucubin may be a useful therapeutic compound for the human peripheral nervous system after various nerve injuries.
"After 2 h, viruses were washed off and cells were incubated in standard culture media for 40– 48 h. The expressed b-galactosidase was visualized in X-gal staining as described . For enzyme assays, cells in 6-well plates were lysed in reporter lysis buffer and assayed for the enzyme activity according to the manufacturerÕs instructions (Promega). "
[Show abstract][Hide abstract] ABSTRACT: One impediment to treating neuronal diseases is finding ways to introduce genes into specific neuroglial cell types. Here we describe the strategy for efficient gene delivery via transferrin receptor using an adenovirus bearing a peptide mimic for transferrin. The attachment of the peptide consisted of 12 amino acids on the C-terminus of adenovirus fiber protein significantly improved entry and expression of a beta-galactosidase transgene into neuroglial cells such as astrocytes, and Schwann cells. The entry of re-targeted viruses into cells depends on the attached peptide and the transferrin receptor. Furthermore, transferrin did not affect gene delivery by the engineered adenovirus, suggesting that the effectiveness of therapeutic agents targeted to the receptor would not be diminished by competition with the abundant endogenous transferrin present in the plasma. Therefore, such transduction systems hold promise for efficient delivering gene to neuroglial cells in gene therapy protocols.
Biochemical and Biophysical Research Communications 04/2005; 328(4):1182-7. DOI:10.1016/j.bbrc.2005.01.080 · 2.30 Impact Factor
". Joung et al., (2000) successfully transduced Schwann cells with adenoviruses in vitro and in vivo, demonstrating LacZ gene expression for 5 weeks, during which nerve regeneration was accomplished in a rat model. In vitro studies of dorsal root ganglia sensory neurons of murine and human origin have demonstrated the successful transduction by recombinant adeno-associated adenovirus (rAAV) and vesicular stomatitis protein G-pseudotyped lentivirus vector derived from human immunodeficiency virus (HIV-1) [Fleming et al., 2001]. "
[Show abstract][Hide abstract] ABSTRACT: Gene therapy has been investigated in many aspects of plastic and reconstructive surgery. These areas ultimately involve various forms of tissue healing and the manipulation of bony and soft tissues to reconstruct defects secondary to neoplastic and congenital disorders and trauma. Most research has been limited to animal studies with the exception of clinical trials on the use of gene therapy in lower leg ulcer healing and as an adjunct to advanced recurrent squamous cell carcinoma of the head and neck. Overall, these preliminary studies have produced optimistic results. With the development of more efficient and safer delivery systems, the application of gene therapy in plastic surgery could become more widespread, especially in combination with tissue engineering technology.
Current Gene Therapy 03/2005; 5(1):81-99. DOI:10.2174/1566523052997532 · 2.54 Impact Factor
Francesca Meda, Carole Gauron, Christine Rampon, Jeremie Teillon, Michel Volovitch, Sophie Vriz
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