A Cell Type-Specific and Gap Junction-Independent Mechanism for the Herpes Simplex Virus-1 Thymidine Kinase Gene/Ganciclovir-Mediated Bystander Effect

in Clinical Cancer Research : An Official Journal of the American Association for Cancer Research (1999), 5(11), 3639-44

Tumor cells expressing the herpes simplex virus type 1 thymidine kinase (HSV-tk) gene are killed by nucleoside analogues such as ganciclovir (GCV). GCV affects not only the cells expressing HSV-tk but ... [more ▼]

Tumor cells expressing the herpes simplex virus type 1 thymidine kinase (HSV-tk) gene are killed by nucleoside analogues such as ganciclovir (GCV). GCV affects not only the cells expressing HSV-tk but also neighboring cells that do not express the gene; this phenomenon commonly is called "bystander effect." GCV metabolites transfer via gap junctional intercellular communication (GJIC) accounts for the bystander effect in different cell lines, but other mechanisms have also been described. In this study, we analyzed the mechanisms of the bystander effect in two cell lines exhibiting different capacities of communication (DHD/K12 and 9L). The 9L cells exhibited a very good bystander effect, which was completely blocked by a long-term inhibitor of GJIC, 18 alpha-glycyrrhetinic acid. DHD/K12 cells exhibited a moderate bystander effect that was not abolished by 18 alpha-glycyrrhetinic acid or 1-octanol, another strong inhibitor of GJIC. Interestingly, we also observed a bystander effect in cultures where HSV-tk-expressing DHD/K12 cells were physically separated from their untransfected counterparts but grown in the same medium. Moreover, the transfer of filtered conditioned medium from GCV-treated HSV-tk-expressing DHD/K12 cells to DHD/K12 parental cells induced a decrease of survival in a concentration-dependent manner, suggesting that the bystander effect in this cell line was mediated by a soluble factor. [less ▲]

Effects of Schwann Cell Transplantation in a Contusion Model of Rat Spinal Cord Injury

in Journal of Neuroscience Research (1996), 45(5), 588-597

Cultured Schwann cells were transplanted at various delays into a spinal cord contusion injury performed at low thoracic level in adult female rats. The Schwann cells were purified from the dorsal root ... [more ▼]

Cultured Schwann cells were transplanted at various delays into a spinal cord contusion injury performed at low thoracic level in adult female rats. The Schwann cells were purified from the dorsal root ganglia of adult syngeneic animals. the transplants were well tolerated, and the transplanted Schwann cells invaded the injured spinal cord. As quantified using video image analysis, the survival and growth of the transplanted cells were poor when the grafting procedure was performed 3-4 days after injury and very good when performed immediately or 10 days after injury, in which cases post-traumatic micro- and macrocavitation were strongly reduced. In animals grafted immediately after injury but not in animals grafted after 10 days, post-traumatic astrogliosis was much reduced. The Schwann cells transplanted area was invaded by numerous regenerating axons, the vast majority of which were, based on the neurotransmitter (CGRP and SP) profile, originating from dorsal root ganglion. No regeneration of the corticospinal tract as assessed after anterograde tracing or of descending aminergic fibers could be demonstrated. [less ▲]

Alpha-MSH stimulates neurite outgrowth of neonatal rat corticospinal neurons in vitro.

in Brain Research (1996), 736(1-2), 91-8

Peptides related to melanocortin (alpha MSH) and corticotropin (ACTH), collectively termed melanocortins, exert trophic effects on the outgrowth of neurites from peripheral and central nervous system in ... [more ▼]

Peptides related to melanocortin (alpha MSH) and corticotropin (ACTH), collectively termed melanocortins, exert trophic effects on the outgrowth of neurites from peripheral and central nervous system in vitro. Here we study the neurite outgrowth promoting effect of alpha-MSH on corticospinal (CS) neurons in vitro. Corticospinal neurons were identified in cell culture of neonatal rat cortex by immunostaining of cholera toxin subunit B (CTB), retrogradely transported from the cervical parts of the spinal cord. The CTB-immunoreactive neurons represent a small percentage (3-5%) of the total cell population after 72 h in vitro. The axons or dendrites of cortical and CTB-labelled layer V neurons were visualized using antibodies against axon- or dendrite-specific markers and measured using a semi-automatic quantification device. Here we report that alpha-MSH stimulates axonal as well as dendrite outgrowth from both total and CTB-labelled neurons with a bell-shape response curve. Axonal outgrowth of CTB-labelled neurons was dose-dependently stimulated with a maximal effect of 50% at 10(-10) M alpha-MSH. The maximal effect for stimulation of axon outgrowth for the total cortex population was observed at 10(-8) M alpha-MSH. In addition dendrite outgrowth of both total and CTB-labelled neurons is stimulated in a dose-dependent manner with maximal effects (varying between 46 and 48%) at 10(-8) M alpha-MSH. Explanations in the shift for the optimal alpha-MSH concentration for stimulation of axonal outgrowth of CTB-labelled layer V neurons as compared to total cortex neurons are discussed. [less ▲]

A model of spinal cord injury: the balloon-compressive model

Conference (1995, September 03)

Transplants of syngenic cultured, DRG-derived Schwann cells into the injured adult rat spinal cord.

Conference (1993, June 18)

Les transplantations de cellules de Schwann syngéniques dans les lésions médullaires : Résultats, limitations et perspectives.

Conference (1993)