Cell-based therapy in ischemic stroke

Abstract

Cell-based therapy for stroke represents a third wave of therapeutics for stroke and one focused on restorative processes with a longer time window of opportunity than neuroprotective therapies. An early time window, within the first week after stroke, is an opportunity for intravenously delivered bone marrow and perinatally derived cells that can home to areas of tissue injury and target brain remodeling. Allogeneic cells will likely be the most scalable and commercially viable product. Later time windows, months after stroke, may be opportunities for intracerebral transplantation of neuronally differentiated cell types. An integrated approach of cell-based therapy with early-phase clinical trials and continued preclinical work with focus on mechanisms of action is needed.

Figure 1

The bone marrow is a rich source of stem and progenitor cells. Hematopoietic stem cells (HSC) give rise to CD133+, CD34+, and cells that are both CD34+ and CD133+. Marrow stromal cells (MSC) differentiate into multiple cells types. Rare cell types such as the multipotent adult progenitor cell and MIAMI cells can be expanded in culture and differentiate into cells of all three germ layers. The umbilical cord, the amniotic fluid and the placenta are sources of cell types with regenerative potential.

Figure 2

Depiction of the three “time windows of opportunity” available for stroke. The neuroprotective window is short, lasting hours. The subacute window, is an area of opportunity for intravascularly administered cells by an intra-arterial or intravenous route. Neurotrophic factors will also play an important role in this window. “Chronic stroke” will likely require stereotactic surgical approaches with direct intracerebral delivery of cells differentiated down a neuronal lineage.