A Look into Stem Cell Therapy: Exploring the Options for Treatment of Ischemic Stroke

Abstract

Neural stem cells (NSCs) offer a potential therapeutic benefit in the recovery from ischemic stroke. Understanding the role of endogenous neural stem and progenitor cells under normal physiological conditions aids in analyzing their effects after ischemic injury, including their impact on functional recovery and neurogenesis at the site of injury. Recent animal studies have utilized unique subsets of exogenous and endogenous stem cells as well as preconditioning with pharmacologic agents to better understand the best situation for stem cell proliferation, migration, and differentiation. These stem cell therapies provide a promising effect on stimulation of endogenous neurogenesis, neuroprotection, anti-inflammatory effects, and improved cell survival rates. Clinical trials performed using various stem cell types show promising results to their safety and effectiveness on reducing the effects of ischemic stroke in humans. Another important aspect of stem cell therapy discussed in this review is tracking endogenous and exogenous NSCs with magnetic resonance imaging. This review explores the pathophysiology of NSCs on ischemic stroke, stem cell therapy studies and their effects on neurogenesis, the most recent clinical trials, and techniques to track and monitor the progress of endogenous and exogenous stem cells.

Figure 1

This figure demonstrates neurogenesis of endogenous neural stem cells. (1) Neurogenesis and proliferation occur in the SVZ and SGZ on the lateral ventricle and hippocampus, respectively. (2) NSPC migration occurs through the rostral migratory stream to the olfactory bulb, where neuroblasts migrate as interneurons through specific cell layers. From the SGZ, NSPCs migrate to the inner granule cell layer. (3) Differentiation occurs once neuroblasts reach glomeruli within the olfactory bulb or the inner granule cell layer. The majority of SVZ-derived neuroblasts become GABAergic granule neurons. After complete differentiation and maturation of neuroblasts from the SGZ, new neurons possess GABAergic and glutamatergic characteristics.

Figure 2

This figure demonstrates the process of neurogenesis following ischemic injury in a coronal section of the brain. Endogenous NSCs proliferate and migrate from the SVZ to areas of ischemic injury. Once they are outside the SVZ, they are able to undergo differentiation into oligodendrocyte progenitors, astrocytes, and neuroblasts.

Figure 3

This figure demonstrates the effects of ESC transplantation into the brain. When ischemic stroke occurs, ESCs promote neuronal differentiation in both neurogenic and nonneurogenic regions, such as the striatum. ESCs are able to respond to environmental changes after ischemic insult and improve the capacity to promote neurogenesis.

Figure 4

This figure demonstrates the effects of NSC transplantation following ischemic injury in a rat brain. Exogenous NSCs promote increased migration and proliferation of endogenous NSCs. In addition, there is increased differentiation into neurons compared to glial cells.

Figure 5

This figure demonstrates the differentiation capacities of mesenchymal stem cells. They are multipotent cells and can differentiate into mesodermal, endodermal, and ectodermal cell types. This includes the ability to become neurons, an important characteristic for the study of ischemic stroke and stem cells.

Figure 6

This figure demonstrates the capabilities of inducible pluripotent stem cells (iPSCs). Human iPSCs can be directed in vitro to the NSC phenotype. They are then injected into the cerebrum following MCAO and ischemic injury in rats. iPSCs are able to proliferate and differentiate primarily into neurons.

Figure 7

This figure demonstrates the effects of using cotransplantation as a method for stem cell therapy. An example of this approach is using endothelial progenitor cells (EPCs) and NSCs. Together, they create a synergistic effect that results in an increase in VEGF and BDNF. This activates the PI3K/Akt pathway that is thought to protect cerebral endothelial cells from hypoxia/reoxygenation injury during ischemic stroke.