LAUSR

The promise of cellular therapies as a treatment for stroke and other injuries and diseases of the central nervous system (CNS) has compelled researchers, clinicians, patients, and the public for the last 2 decades. Various types of cells isolated from numerous tissue sources have demonstrated benefit in improving outcomes in animal stroke models when administered intravenously in an acute time frame (minutes to days) after stroke onset. Data supporting the homing of cells to the brain and proximal to the infarct after intravenous administration is lacking, begging the question “How are cells from an array of tissue sources functioning to improve neurological recovery without the presence of the cells at the primary site of injury?” The last 10 years have seen an increased focus on understanding the importance the peripheral immune system plays in exacerbating and complicating treatment and recovery of patients with stroke. Based on seminal observations from the Willing, Pennypacker, and Offner laboratories, we now know that the spleen participates in the immune response in the acute time frame after stroke onset in animal studies, and the involvement of spleen has now been confirmed in observational human stroke studies.1–3 The accumulation of laboratory and clinical data supports the contention that acute intravenous administration of cell therapies provides long-term benefit after stroke by modulating the initial peripheral immune response, potentiating tissue repair and recovery, and these data may collectively signal the emergence of a new class of therapies for the treatment of ischemic stroke. After the initial injury in the brain after ischemic stroke, a complex set of inflammatory cascades are initiated resulting in the engagement of both innate and adaptive immune systems. Glial cells—the endogenous phagocytic immune cells of the brain—become activated and in concert with the injured parenchymal tissue, signal the peripheral immune system …