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The Rise of Cell Therapies to Repair Stroke Damage

A perfect world would include the means to prevent catastrophic failures of brain structure such as stroke from ever happening. One such means is a working implementation of the rejuvenation biotechnologies evisaged in detail in the SENS research plans. Strokes and other failures happen because tissue becomes damaged and frail. Remove that damage and the stroke risk of an old person would be that of a young person, which is to say very close to zero. Rejuvenation therapies lie a number of years in the future, however, where that number is very much determined by how much funding and support are dedicated to the right sort of research today. In the meanwhile, the present state of the art in medical technology, absent any way to greatly impact aging and the harm it causes, is to build better ways to clean up and restore more function after a stroke occurs.

The most promising lines of research in restorative therapies for stroke patients involve the manipulation and transplant of cells. Scientists are finding ways to spur native cells to greater feats of regeneration, or to bring in new cells that can do the job where native cells will not. I'm sure that you're all familiar with work on stem cell transplants of one form or another, for example, but there are many more strategies under development. On this topic a recent open access review notes the growth in clinical trials for stroke treatments in the past few years. At some point all of the promising work in the laboratory and all of the experience gained in treatments available via medical tourism will start to push its way into the highly regulated, expensive, slow-moving mainstream of clinical translation:

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

Stroke is responsible for 11.1% of all deaths, and is the second leading cause of death worldwide after ischemic heart disease. The injury produced by stroke is largely complete after 24-48 h, and neuroprotective therapies that must be administered within a time window such as 3-6 h are difficult to apply in clinical practice. Approximately 80% of all strokes are ischemic, and currently, tissue plasminogen activator (tPA) is the only pharmacological agent approved for treatment of acute ischemic stroke. However, tPA therapy has important limitations, notably the narrow therapeutic window of 4.5 h, which limits its use to a small minority (2% to 4%) of patients. Moreover, tPA prevents disability in only six patients per 1000 ischemic strokes, and does not reduce the mortality rate.

On the other hand, neurorestorative therapies, including cell therapies, seek to enhance regenerative mechanisms such as angiogenesis, neurogenesis, and synaptogenesis, and have been investigated extensively in the preclinical models of ischemia. Neurorestorative cell therapies can be grossly divided into endogenous or exogenous. Endogenous therapies are those that aim to stimulate, for example, bone marrow-cell migration to the blood stream, with pharmacological agents such as granulocyte-colony stimulating factor (G-CSF). The exogenous approach involves the injection of a variety of cells to produce structural or functional benefits. Although excellent reviews have been recently made on different aspects of cell therapies for stroke, there has been a dramatic increase in the number of published and registered trials in the past years that has not been comprehensively assessed.

Several preclinical studies have indicated that there is a structural and/or functional recovery after intracerebral, intra-arterial, and intravenous therapy with different cell types. Although clinical results with other ischemic diseases and preclinical studies for stroke are encouraging, there are still many questions regarding the possible mechanisms of action of the cells and the optimal treatment protocol. One of the main questions to be answered is related to the best cell type to be used in these patients. Further, aspects such as the mechanisms [that produce] improvements and the optimal treatment protocol are not yet fully understood and require further evaluation. Nevertheless, different clinical studies, the majority of them small, nonrandomized and uncontrolled, have now been reported and indicate that cell therapy seems safe, feasible, and potentially efficacious. The increasing number of ongoing studies, including large randomized double-blind studies, have the potential to determine the efficacy of cell therapy for stroke and to translate the preclinical findings into clinical practice.

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