Cerebral ischemia is a major cause of morbidity and mortality in the aged population, as well as a tremendous burden on the healthcare system. Despite timely treatment with thrombolysis and percutaneous intravascular interventions, many patients are often left with irreversible neurological deficits. Bone marrow stromal cells (BMSCs), also referred to as mesenchymal stem cells (MSCs), are a type of nonhematopoietic stem cells which exists in bone marrow mesh, with the potential to self-renew. Unlike cells in the central nervous system, BMSCs differentiate not only into mesodermal cells, but also endodermal and ectodermal cells. Moreover, it has been reported that BMSCs develop into cells with neural and vascular markers and play a role in recovery from ischemic stroke. These findings have fuelled excitement in regenerative medicine for neurological diseases, especially for ischemic stroke. There is now preclinical evidence to suggest that BMSCs grafted into the brain of ischemic models abrogate neurological deficits. Based on the overwhelming evidence from animal studies as well as in clinical trials, BMSC transplantation is considered a promising strategy for treatment of ischemic stroke. The goal of this review is to present an integrated consideration of molecular mechanisms in a chronological fashion and discuss an optimal BMSC delivery route for ischemic stroke.

Cerebral ischemia remains the most frequent cause of death and quality-of-life impairments due to neurological deficits, and accounts for the majority of total healthcare costs. However, treatments for cerebral ischemia are limited. Over the last decade, bone marrow stromal cell (BMSC) therapy has emerged as a particularly appealing option, as it is possible to help patients even when initiated days or even weeks after the ischemic insult. BMSCs are a class of multipotent, self-renewing cells that give rise to differentiated progeny when implanted into appropriate tissues. Therapeutic effects of BMSC treatment for ischemic stroke, including sensory and motor recovery, have been reported in pre-clinical studies and clinical trials. In this article, we review the recent progress in BMSC-based therapy for ischemic stroke, focusing on the route of delivery and pre-processing of BMSCs. Selecting an optimal delivery route is of particular importance. The ideal approach, as well as the least risky, for translational applications still requires further identification. Appropriate preprocessing of BMSCs or combination therapy has the benefi t of achieving the maximum possible restoration. Further pre-clinical studies are required to determine the time-window for transplantation and the appropriate dosage of cells.