Stem Cells and Stress Injury: Role of Arginine Decarboxylase

The use of stem cells in cell replacement therapy for neurodegenerative diseases has received a great deal of scientific and public interest in recent years. Oxidative stress, toxic byproducts, which prevails in the microenvironment during the diseased condition, may limit the survival of the transplanted stem cells affecting tissue regeneration and even longevity. Recently, it has become clear that balanced regulation of reactive oxygen species is of critical significance for cell fate determination as well as for stem cell differentiation, function, and survival following transplantation in injured tissues. Recent evidences suggested that genetically modified stem cells with antioxidant genes could exert stem cell protection and their potential for central nervous system (CNS) maladies treatment. Incorporating this knowledge into designs of novel approaches for stem cell protection is a major issue now. Polyamines are ubiquitous components in all living organisms that play essential roles in growth and signal transduction. The polyamine biosynthetic pathway is established as a valid target for the synthesis of drugs. Several comprehensive review articles have described arginine decarboxylase (ADC) as a component of the polyamine pathways metabolizing arginine and the presence of ADC as a means of generating agmatine which is an endogenous primary amine and a novel neuromodulator and possess neuroprotective properties. The presence of an ADC-regulated pathway to agmatine synthesis would also need to be considered in the interpretation of studies in which gene transfer approaches to increase or decrease agmatine levels both in in vitro and in vivo studies. Agmatine synthesized from the decarboxylation of l-arginine catalysed by arginine decarboxylase (ADC). Recently it was demonstrated that retrovirus containing ADC gene transfer which can synthesize agmatine endogenously conferred protection against toxic insult in neural stem cells. This article summarizes the results demonstrating the various gene transfer effects which can allow for stem cell protection. This review unravels the impact for development and design of genetically engineered stem cells for future cell therapies.