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Biomedical subjects

Leslie P Weiner

Publications and source records attributed to Leslie P Weiner.

3 recordsLinked to original sources

Applications of microfluidics for neuronal studies.

Microfabrication processes have changed the technology used in consumer goods, and have now advanced into applications in biology. Microfluidic platforms are microfabricated tools that are gaining popularity for studies of molecular and cellular biology. These platforms can allow precise control of the environment surrounding individual cells and they have been used to study physiologic and pharmacologic responses at the single-cell level. This article reviews microfluidic technology with emphasis on advances that could apply to the study of the nervous system, including architecture for isolation of axons, integrated electrophysiology, patterned physical and chemical substrate cues, and devices for the precisely controlled delivery of possible therapeutic agents such as trophic factors and drugs. The potential of these chips for the study of neurological diseases is also discussed.

Animals↗

Gene therapy in a murine model for clinical application to multiple sclerosis.

Female SJL/J mice, suffering from experimental autoimmune encephalomyelitis (EAE), were injected with 1 x 10(7) cells from a syngeneic fibroblast line transduced with a retroviral vector designed to encode proteolipid protein (101-157) targeted for secretion. A striking abrogation of both clinical and histological signs of disease resulted. The treatment was efficacious when given after the first or the third relapses, protected naive mice from challenge with spinal cord homogenate, and was dose dependent. This strategy was devised to provide a systemic, antigen-specific signal to pathogenic T cells in the absence of costimulation and, hence, render them anergic. Cytokine analyses of brain and spinal cord lymphocytes demonstrate that the treatment induces an antiinflammatory Th2 profile, indicating that this antigen-specific therapy acts by a cytokine-induced pathway. This study was designed for translation to the clinic. We envision using allogeneic transduced fibroblasts, encapsulated in a chamber, to deliver the antigen-specific signal. This will enable us to use one therapeutic cell line for all patients and to remove the device should the therapy exacerbate disease.

Animals↗

Increased CXCL8 (IL-8) expression in Multiple Sclerosis.

Multiple Sclerosis (MS) is a chronic inflammatory disease of the CNS which is characterized by large mononuclear cell infiltration and significant demyelination. CXCL8 is a chemo-attractant for both neutrophils and monocytes and triggers their firm adhesion to endothelium. In this study, we demonstrate that serum CXCL8 and CXCL8 secretion from PBMCs are significantly higher in untreated MS patients compared to controls and are significantly reduced in MS patients receiving interferon-beta1a therapy. We suggest that CXCL8 may serve as a marker of monocyte activity in MS and may play a role in monocyte recruitment to the CNS.

Adult↗