Considerations for tissue-engineered and regenerative medicine product development prior to clinical trials in the United States.

Tissue-engineered and regenerative medicine products are promising innovative therapies that can address unmet clinical needs. These products are often combinations of cells, scaffolds, and other factors and are complex in both structure and function. Their complexity introduces challenges for product developers to establish novel manufacturing and characterization techniques to ensure that these products are safe and effective prior to clinical trials in humans. Although there are only a few commercial products that are currently in the market, many more tissue-engineered and regenerative medicine products are under development. Therefore, it is the purpose of this article to help product developers in the early stages of product development by providing insight into the Food and Drug Administration (FDA) process and by highlighting some of the key scientific considerations that may be applicable to their products. We provide resources that are publically available from the FDA and others that are of potential interest. As the provided information is general in content, product developers should contact the FDA for feedback regarding their specific products. Also described are ways through which product developers can informally and formally interact with the FDA early in the development process to help in the efficient progression of products toward clinical trials.

The effects of stress on memory cytotoxic T lymphocyte-mediated protection against herpes simplex virus infection at mucosal sites.

Psychological stress has been shown to affect many components of the innate and adaptive immune responses to a variety of pathogens including herpes simplex virus (HSV). Mucosal tissues are clinically relevant sites of infection with HSV as well as with many other common pathogens. However, there is a scarcity of experimental evidence that stress affects mucosal immunity. We have taken advantage of a murine model of HSV-specific immune protection that is mediated by only memory cytotoxic T lymphocytes (CTLm) specific for a single CTL recognition epitope within glycoprotein B of HSV-1 (gB498-505). This CTLm population is elicited by vaccination with a recombinant vaccinia virus, which expresses this epitope in the absence of any other HSV-encoded antigens. We report here that stress reduces the ability of gB498-505-specific CTLm to protect against a lethal intranasal or intravaginal HSV infection. Also, stress decreases the ability of these CTLm to limit virus levels at the mucosal site of infection but does not have a significant effect on the levels of virus in the innervating sensory ganglia. Finally, stress decreases protection against HSV-mediated pathology of the vaginal epithelium. These studies are the first to examine the effects of stress on CTLm activation and function in vivo.