Potential therapeutic roles of stem cells in ischemia-reperfusion injury.

Ischemia-reperfusion injury (I/RI), produced by an initial interruption of organ blood flow and its subsequent restoration, contributes significantly to the pathophysiologies of stroke, myocardial infarction, renal I/RI, intestinal I/RI and liver I/RI, which are major causes of disability (including transplant failure) and even mortality. While the restoration of blood flow is required to restore oxygen and nutrient requirements, reperfusion often triggers local and systemic inflammatory responses and subsequently elevate the ischemic insult where the duration of ischemia determines the magnitude of I/RI damage. I/RI increases vascular leakage, changes transcriptional and cell death programs, drives leukocyte entrapment and inflammation and oxidative stress in tissues. Therapeutic approaches which reduce complications associated with I/RI are desperately needed to address the clinical and economic burden created by I/RI. Stem cells (SC) represent ubiquitous and uncommitted cell populations with the ability to self-renew and differentiate into one or more developmental 'fates'. Like immune cells, stem cells can home to and penetrate I/R-injured tissues, where they can differentiate into target tissues and induce trophic paracrine signaling which suppress injury and maintain tissue functions perturbed by ischemia-reperfusion. This review article summarizes the present use and possible protective mechanisms underlying stem cell protection in diverse forms of ischemia-reperfusion.