Effective gene transfer into regenerating sciatic nerves by adenoviral vectors: potentials for gene therapy of peripheral nerve injury.
ABSTRACT 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.
- [show abstract] [hide abstract]
ABSTRACT: Surgical repair of severe peripheral nerve injuries represents not only a pressing medical need, but also a great clinical challenge. Autologous nerve grafting remains a golden standard for bridging an extended gap in transected nerves. The formidable limitations related to this approach, however, have evoked the development of tissue engineered nerve grafts as a promising alternative to autologous nerve grafts. A tissue engineered nerve graft is typically constructed through a combination of a neural scaffold and a variety of cellular and molecular components. The initial and basic structure of the neural scaffold that serves to provide mechanical guidance and optimal environment for nerve regeneration was a single hollow nerve guidance conduit. Later there have been several improvements to the basic structure, especially introduction of physical fillers into the lumen of a hollow nerve guidance conduit. Up to now, a diverse array of biomaterials, either of natural or of synthetic origin, together with well-defined fabrication techniques, has been employed to prepare neural scaffolds with different structures and properties. Meanwhile different types of support cells and/or growth factors have been incorporated into the neural scaffold, producing unique biochemical effects on nerve regeneration and function restoration. This review attempts to summarize different nerve grafts used for peripheral nerve repair, to highlight various basic components of tissue engineered nerve grafts in terms of their structures, features, and nerve regeneration-promoting actions, and finally to discuss current clinical applications and future perspectives of tissue engineered nerve grafts.Progress in Neurobiology 02/2011; 93(2):204-30. · 9.04 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Berberine, an isoquinoline alkaloid component of Coptidis Rhizoma (goldenthread) extract, has been reported to have therapeutic potential for central nervous system disorders such as Alzheimer's disease, cerebral ischemia, and schizophrenia. We have previously shown that berberine promotes the survival and differentiation of hippocampal precursor cells. In a memory-impaired rat model induced by ibotenic acid injection, the survival of pyramidal and granular cells was greatly increased in the hippocampus by berberine administration. In the present study, we investigated the effects of berberine on neurite outgrowth in the SH-SY5Y neuronal cell line and axonal regeneration in the rat peripheral nervous system (PNS). Berberine enhanced neurite extension in differentiating SH-SY5Y cells at concentrations of 0.25-3 μg/mL. In an injury model of the rat sciatic nerve, we examined the neuroregenerative effects of berberine on axonal remyelination by using immunohistochemical analysis. Four weeks after berberine administration (20 mg/kg i.p. once per day for 1 week), the thickness of remyelinated axons improved approximately 1.4-fold in the distal stump of the injury site. Taken together, these results indicate that berberine promotes neurite extension and axonal regeneration in injured nerves of the PNS.Journal of medicinal food 02/2012; 15(4):413-7. · 1.39 Impact Factor
- Annals of Physical and Rehabilitation Medicine. 01/2011; 54.