One, Two, Three Steps Toward Cell Therapy for Stroke

Abstract

Background Many clinical trials have failed despite positive laboratory findings. Stroke clinical trials are no exception, with tissue plasminogen activator (tPA) still the only effective drug for stroke with limited therapeutic window. In order to enhance the successful outcome of novel therapies in the clinic, initiatives for translational research guidelines have been pursued. In particular, the advancement of stem cell therapy for stroke from the laboratory to the clinic has now been guided by a set of recommendations called Stem cell Therapeutics as an Emerging Paradigm for Stroke or STEPS. We review here the major criteria for preclinical studies of stem cells arising from the three STEPS meetings in an effort to further emphasize the need for careful and rigorous assessment of the safety, efficacy, and mechanism of action associated with stem cell therapy for stroke. Learning from our previous mistakes and identifying gaps in knowledge will likely prevent stem cell therapy from becoming yet another statistic of failed clinical trial in stroke.

Stem cell therapy for abrogating stroke-induced neuroinflammation and relevant secondary cell death mechanisms

“…However, one of the most disappointing parameters in each of these clinical trials was the functional dosage employed. Preclinical studies of many stem cells, including BM-MSCs, suggest the effective dose range for intravenous delivery is about 4 million cells in a 250 g rat or about 840 million cells for a 75 kg human being (Diamandis and Borlongan, 2015). This means that the dose in these clinical trials was significantly lower than the threshold value needed to recognize any efficacy read-out; 100 million, an average of 600 million, 100 million, and 280.75 million were used in the Bang, Savitz, Banerjee, and Prasad studies, respectively.…”

An update on stem cell therapy for neurological disorders: cell death pathways as therapeutic targets

“…Yet, these developing technologies face obstacles, such as bioethical concerns and misrepresentations, as well as exploitations by the unscrupulous media and business sector, preventing them from reaching full beneficial capacity. Accordingly, a common theme resonating throughout these papers is a push to increase translational research of cell-based therapeutics for clinical applications that will allow scientifically sound assessments of cell therapy, delineating hype from hope [40][41][42][43][44][45][46][47][48]. Forthcoming updates on the ongoing clinical trials of cell therapy will provide valuable information on which to build the future of stem cell research and therapeutic applications.…”

Mesenchymal stem cell-based therapy for ischemic stroke

“…In addition to the small number of patients enrolled in these clinical trials, the translation of laboratory protocols for clinical transplant regimens has been marred with major discrepancies including the lack of well-defined release criteria of the donor cells, varying timing, cell dose and route of transplant intervention, altogether deviating from the established preclinical readouts. In particular, many of the clinical trials were not performed along the guidelines of Stem cell Therapeutics as an Emerging Paradigm for Stroke or STEPS lab-to-clinic translational guidelines [82]. The recommended translational research approach is to use at least two models of stroke using small animals (rodents).…”