Regeneration after stroke: Stem cell transplantation and trophic factors

Stroke is a leading cause of death and disability worldwide. However, there is only one Food and Drug Administration-approved drug for the treatment of ischemic stroke, i.e., tissue plasminogen activator, and its therapeutic window is limited to within 4.5 h after stroke. Since clinical trials for neuroprotection have failed to demonstrate efficacy, multipotent and pluripotent stem cell transplantations are viable candidates for stroke treatment by providing trophic factor support and/or cell replacement following injury. The goal of this review is to highlight the promise of stem cell transplantation as vehicles for trophic factor delivery. The beneficial effects of different stem cell types as transplants as well as ways to upregulate trophic factors in stem cells are described in this review. Stem cell transplantation has consistently shown beneficial effects in the ischemic stroke model, in part due to the beneficial factors that stem cells release around the stroke injury area, resulting in smaller infarct volumes and regeneration and functional recovery. Upregulation of beneficial factors in stem cells and neural progenitors before transplantation has been shown to be even more effective in treating the stroke injury than stem cells without upregulated factors. However, for both stem cells and genetic engineering, there remain many unanswered questions and potential for improvement. These include modifiable parameters such as the different stem cell types and different factors, as well as the various readouts for investigation, such as various in vivo effects, such as immune system modulation and enhancement of endogenous neurogenesis and angiogenesis.