The Rise of Cell Therapy Trials for Stroke: Review of Published and Registered Studies

Abstract

Stroke is the second leading cause of death and the third leading cause of disability worldwide. Approximately 16 million first-ever strokes occur each year, leading to nearly 6 million deaths. Nevertheless, currently, very few therapeutic options are available. Cell therapies have been applied successfully in different hematological diseases, and are currently being investigated for treating ischemic heart disease, with promising results. Recent preclinical studies have indicated that cell therapies may provide structural and functional benefits after stroke. However, the effects of these treatments are not yet fully understood and are the subject of continuing investigation. Meanwhile, different clinical trials for stroke, the majority of them small, nonrandomized, and uncontrolled, have been reported, and their results indicate that cell therapy seems safe and feasible in these conditions. In the last 2 years, the number of published and registered trials has dramatically increased. Here, we review the main findings available in the field, with emphasis on the clinical results. Moreover, we address some of the questions that have been raised to date, to improve future studies.

Stem and Progenitor Cell-Based Therapy of the Central Nervous System: Hopes, Hype, and Wishful Thinking

“…Stroke in particular has been assessed by many groups as a potential target for cell replacement, and was among the first targets of stem and progenitor cell-based transplantation. (Hara et al, 2008; Nelson et al, 2002; Rosado-de-Castro et al, 2013). Yet stroke occurs in a fundamentally compromised environment of ischemic infarct, often in regions that have suffered chronic hypoxic ischemia, with its attendant gliosis and inflammation.…”

Transplantation of Induced Pluripotent Stem Cells Alleviates Cerebral Inflammation and Neural Damage in Hemorrhagic Stroke

“…Multiple types of stem cells such as neural stem cells (NSCs) and MSCs have so far shown potent immunomodulatory and neuroprotective properties in the models of human ischemic and hemorrhagic stroke[14, 29, 30, 34–36]. For example, Lee et al [5] reported that intravenously injected NSCs have neuroprotective and anti-inflammatory actions in hemorrhagic stroke.…”

Neuroprotective delivery platforms as an adjunct to mechanical thrombectomy

“…80 Although stem cells are neuroregenerative, rather than neuroprotective, their intraarterial delivery is worth considering in this discussion. At this time, the optimal mode of stem cell delivery (intracerebral, intraventricular, subarachnoid, intraarterial, intraperitoneal, intravenous, and intranasal) remains unclear.…”