Developing Cellular Therapies for Stroke

Abstract

Cell therapies refer to the use of cells or cellular material that exert a treatment effect in animal models of disease. During the past 15 years, a range of different types of cell therapies has emerged as potential new treatments that are under development for stroke and other neurological disorders. The past quarter century has witnessed the success of thrombolytic therapy and the failure of neuroprotective agents for acute ischemic stroke. These therapeutic strategies often target a single pathway (tissue-type plasminogen to dissolve clots in the former case and specific biochemical pathways of injury in the latter). Cell therapies represent an entirely different biopharmaceutical approach. In stroke, there are 2 broad goals for the therapeutic application of cell-based therapies. The first is to transplant cells, usually by direct injection to the brain, to graft and create new tissue that may restore neuronal connections damaged or lost in a stroke. In the 1990s, several groups of investigators initially pursued this goal to transplant grafted cells in patients with chronic stroke.1,2 However, cell transplantation with the intention of engraftment is likely going to require extensive preclinical work to address several biological challenges that many investigators are actively pursuing. Those challenges to use cells and recreate lost circuitry after a stroke are well described by Dihne et al.3 The second goal, which is the focus of this review, has more immediate clinical applications in which exogenous cells administered to the body cause a range of paracrine and immunomodulatory effects, the end result of which leads to a reduction in secondary injury processes and stimulation of brain repair after stroke (Figure). Figure. Various temporal windows can be envisioned that provide different mechanistic targets for cell therapies in stroke. The types of cell therapies under development range from embryonic/fetal sources (embryonic …