Insight Into the Mechanisms and the Challenges on Stem Cell-Based Therapies for Cerebral Ischemic Stroke.

Huiyong Liu,Yue He,Yibo Ou,Xiangyue Zhou,Sydney Reiter,Cameron Lenahan,Hanmin Chen

doi:10.3389/fncel.2021.637210

Abstract

Strokes are the most common types of cerebrovascular disease and remain a major cause of death and disability worldwide. Cerebral ischemic stroke is caused by a reduction in blood flow to the brain. In this disease, two major zones of injury are identified: the lesion core, in which cells rapidly progress toward death, and the ischemic penumbra (surrounding the lesion core), which is defined as hypoperfusion tissue where cells may remain viable and can be repaired. Two methods that are approved by the Food and Drug Administration (FDA) include intravenous thrombolytic therapy and endovascular thrombectomy, however, the narrow therapeutic window poses a limitation, and therefore a low percentage of stroke patients actually receive these treatments. Developments in stem cell therapy have introduced renewed hope to patients with ischemic stroke due to its potential effect for reversing the neurological sequelae. Over the last few decades, animal tests and clinical trials have been used to treat ischemic stroke experimentally with various types of stem cells. However, several technical and ethical challenges must be overcome before stem cells can become a choice for the treatment of stroke. In this review, we summarize the mechanisms, processes, and challenges of using stem cells in stroke treatment. We also discuss new developing trends in this field.

Highlights

Stroke is a leading cause of functional impairment and death worldwide (Meschia et al, 2014)
Transplantation of stem cells whose genes have been modified using viruses to express neurotrophic and growth factors, such as brainderived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), nerve growth factor (NGF), GDNF, Noggin, placental growth factor (PIGF), hepatocyte growth factor (HGF), erythropoietin (EPO), angiopoietin-1 (ANG-1), and IL-10 has been proven to be more effective in promoting neuronal tissue regeneration compared to the unmodified stem cells in experimental stroke animal models (Wang et al, 2004; Ding et al, 2011; Chen et al, 2013; Nakajima et al, 2017; Wang et al, 2018; Moxon et al, 2019)
Several studies have shown that various types of stem/progenitor cells and their derivatives can be more effective than a single type of stem cell for the reconstruction of damaged neural tissue after ischemic stroke, as different neurotrophic factors could be secreted by different cells

Summary

Introduction

Stroke is a leading cause of functional impairment and death worldwide (Meschia et al, 2014). Multiple potential mechanisms are involved in stem cell-based therapy for ischemic stroke (Figure 1), including cell migration and neurotrophic secretion, apoptosis and inflammation inhibition, angiogenesis, and neural circuit reconstruction.

Results

Conclusion