Ischemic stroke is characterized by acute loss of neurons, various glia and the disruption of synaptic architecture. Here, we discuss the potential use of pluripotent stem cells to surpass the efficacy of current treatments.
A frightful cascade of events is involved in neural cell death, or apoptosis, in brains of stroke patients including calcium influx into cells, impaired mitochondria, oxygen and glucose depletion, and glutamate excitotoxicity. As if that weren’t enough, further damage comes with the subsequent release of reactive oxygen species, as well as the disruption of the blood-brain barrier by the release of proteases from endothelial cells and the resulting infiltration of immune cells. Cytokines released by these immune cells then lead to inflammatory reactions and even more increased brain injury.
The high morbidity, mortality and disability rates in patients suffering ischemic stroke has been a longstanding clinical challenge and takes a staggering toll on patients, their families and support communities. A typical course of clinical management may include a variety of approaches including thrombolytic therapy, percutaneous intravascular interventions, behavioral rehabilitation, and pharmacotherapy. Many patients suffering from stroke, however, remain disabled in spite of these interventions. The dependence of timing and technical expertise of these treatments contributes to poor clinical outcomes.
Clearly, there is a need for radical new therapies for ischemic stroke and among the most promising are pluripotent stem cell based approaches. Pluripotent stem cell therapy is currently being developed for several diseases, including diabetes. Basic and translational research thus far have focused on three types of stem cells including embryonic stem cell (ESCs), neural stem cells (NSCs), and mesenchymal stem cells (MSCs). Naturally induced neurogenesis by endogeneous NSCs is found in several stroke models, but the number and survival rate of new neurons derived from endogeneous neurogenesis are low and the new neurons are insufficient to replace those lost.
Clinical studies have demonstrated the high efficiency and safety of pluripotent stem cells (especially MSCs) for stroke management. The ameliorative effects of stem cells might be rooted in multiple mechanisms including cell replacement, neuroprotection, endogenous neurogenesis, angiogenesis, and modulation of inflammation and immune responses.
But some unknowns and deficiencies have to be addressed before clinical application. Complications that still need to be overcome include cell homing, survival, tracking, optimal cell transplantation protocols, adverse event monitoring, and treatment management. Better understanding of the mechanisms of pluripotent stem cells in treating ischemic stroke will help resolve many of these issues.
 Lei Hao, Zhongmin Zou, Hong Tian, Yubo Zhang, Huchuan Zhou, Lei Liu Stem Cell-Based Therapies for Ischemic Stroke Biomed Res Int. 2014; 2014: 468748. doi: 10.1155/2014/468748