Intravascular Stem Cell Transplantation for Stroke

Abstract

Stroke is the third leading cause of death and the leading cause of adult disability in North America. Emphasis has been placed on developing treatments that reduce the devastating long-term impacts of this disease, and preclinical research on stem cell therapy has demonstrated promising results. However, questions about the optimal cell delivery method and timing of cell transplantation are not fully answered. Recent findings suggest that intravascular stem cell delivery is a safe and efficacious alternative to stereotactic cell injections. It also offers advantages should repeat treatments prove beneficial. Recent reports further suggest that intra-arterial injection results in a wider distribution of cells throughout the stroked hemisphere with a significantly greater cell engraftment compared to intravenous injection. In this review, we describe the benefits and potential risks associated with intravascular stem cell delivery and compare intra-arterial to intravenous cell transplantation methods. We discuss the importance of cell biodistribution and timing of transplantation in driving cell survival. We examine current proposed mechanisms involved in cell migration and functional recovery and discuss future directions for intravascular stem cell therapy research.

Intra-Arterial Delivery of Cell Therapies for Stroke

“…The main reason for this is that cells bypass filtering organs, such as the lung, the spleen, and the liver 3 . Pre-clinical studies have also demonstrated that targeted delivery to the ischemic brain has well-defined molecular mechanisms, attracting cells from the intravascular to the intraparenchymal space 4 . Cell-sorting or cell engineering to improve the targeted delivery needs to be further investigated.…”

Cell-Based Therapy in TBI: Magnetic Retention of Neural Stem Cells in Vivo

“…Stem cell transplantation into the adult central nervous system (CNS) as cellular therapy has been suggested for treatment of neurodegenerative diseases such as Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS), CNS trauma disorders such as spinal cord injury (SCI) and traumatic brain and axonal injury, as well as stroke and brain tumors (1,5,17,30,33,45,47,48,51). In animal models of traumatic brain injury (TBI), recent studies have demonstrated transplantation of several types of stem cells for potential therapy, and stem cell-based therapies are being evaluated for safety and efficacy in humans (ClinicalTrials.gov Identifier: NCT02028104).…”

BDNF Pretreatment of Human Embryonic-Derived Neural Stem Cells Improves Cell Survival and Functional Recovery after Transplantation in Hypoxic–Ischemic Stroke

“…In the field of intravascular neural stem cell (NSC) transplantation, our lab has shown a direct correlation between the number of cells surviving in the brain after intra-arterial (IA) transplantation and positive functional outcomes (13). However, intravascular transplantation of human NSCs into rodents has often demonstrated a very low rate of cell engraftment (5). Therefore, we sought a way to improve cell engraftment following transplantation in the hopes of improving functional outcomes after stroke.…”