Stem Cell‐Based Therapies for Ischemic Stroke: Preclinical Results and the Potential of Imaging‐Assisted Evaluation of Donor Cell Fate and Mechanisms of Brain Regeneration

Abstract

Stroke is the second most common cause of death and is a major cause of permanent disability. Given the current demographic trend of an ageing population and associated increased risk, the prevalence of and socioeconomic burden caused by stroke will continue to rise. Current therapies are unable to sufficiently ameliorate the disease outcome and are not applicable to all patients. Therefore, strategies such as cell-based therapies with mesenchymal stem cell (MSC) or induced pluripotent stem cell (iPSC) pave the way for new treatment options for stroke. These cells showed great preclinical promise despite the fact that the precise mechanism of action and the optimal administration route are unknown. To gain dynamic insights into the underlying repair processes after stem cell engraftment, noninvasive imaging modalities were developed to provide detailed spatial and functional information on the donor cell fate and host microenvironment. This review will focus on MSCs and iPSCs as types of widely used stem cell sources in current (bio)medical research and compare their efficacy and potential to ameliorate the disease outcome in animal stroke models. In addition, novel noninvasive imaging strategies allowing temporospatial in vivo tracking of transplanted cells and coinciding evaluation of neuronal repair following stroke will be discussed.

The Role of Astrocytes in Neuroprotection after Brain Stroke: Potential in Cell Therapy

“…Transplantation models have been reported in cerebral ischemia mainly using mesenchymal stem cells (MSC; Hsuan et al, 2016; Lee et al, 2016), induced pluripotent stem cells (iPSCs; Mohamad et al, 2013), and NSCs (Huang et al, 2014; Gervois et al, 2016), showing that there is stimulus of endogenous activity of cells in the injured tissue, generating increased angiogenesis/neovascularization and release of trophic factors, which is chiefly secreted by these cells, allowing the migration to the lesion zone. Likewise, there is axonal recovery, dendritic branching, and synaptogenesis, which are reported mainly surrounding the injury site (Horie et al, 2015).…”

Strategies to improve the migration of mesenchymal stromal cells in cell therapy

“…Potential repair mechanisms involve transdifferentiation to replace damaged neural cells and production of growth factors by MSCs. In addition, infused MSCs could modulate inflammation and stimulate endogenous neural stem cells to migrate to the target region [10,106,116,136,137] . The major obstacles for cell therapies are limited cell availability and engraftment, as well as reduced integration of grafted cells into the host tissue [138] .…”

Allogeneic Umbilical Cord Blood Infusion for Adults with Ischemic Stroke: Clinical Outcomes from a Phase I Safety Study

“…More recently, significant efforts have been made to develop cell‐based therapies that improve recovery following ischemic stroke . Delivery of exogenous human stem cells into animal models for stroke have shown that stem cells survive, are capable of migration and immunomodulation, secrete trophic factors thought to enhance neurogenesis and angiogenesis, reduce infarct volume, and improve outcomes .…”