Genetic and cellular therapies for cerebral infarction.
Neurosurgeons, working as surgical scientists, can have a prominent role in developing and implementing genetic and cellular therapies for cerebral ischemia. The rapid emergence of both genetic and cellular therapies for neural regeneration warrants a careful analysis before implementation of human studies to understand the pitfalls and promises of this strategy. In this article, we review the topic of genetic and cellular therapy for stroke to provide a foundation for practicing neurosurgeons and clinical scientists who may become involved in this type of work. In Part 1, we review preclinical approaches with gene transfer, such as 1) improved energy delivery, 2) reduction of intracellular calcium availability, 3) abrogation of effects of reactive oxygen species, 4) reduction of proinflammatory cytokine signaling, 5) inhibition of apoptosis mediators, and 6) restorative gene therapy, that are paving the way to develop new strategies to treat cerebral infarction. In Part 2, we discuss the results of studies that address the possibility of using cellular therapies for stroke in animal models and in human trials by reviewing 1) the basics of stem cell biology, 2) exogenous and 3) and endogenous cell sources for therapy, and 4) clinical considerations in cell therapy applications. These emerging technologies based on the advancements made in recent years in the fields of genetics, therapeutic cloning, neuroscience, stem cell biology, and gene therapy provide significant potential for new therapies for stroke.
Szentirmai
Oszkar
O
Laboratory of Genetic and Cellular Engineering, and Neurosurgical Service, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
Carter
Bob S
BS
D000818:Animals; D002470:Cell Survival / Q000502:physiology; D064987:Cell- and Tissue-Based Therapy; D002544:Cerebral Infarction / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D051379:Mice; D009410:Nerve Degeneration / Q000235:genetics / Q000503:physiopathology / Q000628:therapy; D009415:Nerve Net / Q000503:physiopathology; D009416:Nerve Regeneration / Q000502:physiology; D009474:Neurons / Q000502:physiology; D011379:Prognosis; D051381:Rats; D033581:Stem Cell Transplantation