Stem cells and stroke

The past decade has seena rise in the number of stem cell-derived therapies targeting ischemic stroke in preclinical and early clinical studies. Corroborated by numerous scientific reports, the therapeutic benefits of stem cells include an extension of the time window for drug intervention, improvement of neurological deficits, reduction of infarct volume, pro-regenerative cerebral reorganization, mitigation of poststroke neuro-inflammation, and tissue restoration, all of which depend on the time after infarct, cell type used, and route of administration13. The wide range of effects observed for stem cell therapies demonstrates that functional recovery after stroke occurs via multiple mechanisms rather than a single target46. Research indicates that the mode of action may depend on the stem cell type and other key factors, including infarct size and location, mode of intervention, and timing poststroke68. Thus, some understanding of the cellular, molecular, and biochemical events that are involved in the mode of action of a stem cell type is a prerequisite to improving and optimizing its therapeutic benefits.

Our 2012 review of cell therapy in stroke showed the wide variety of cell types used preclinically and clinically in stroke treatment research1. Mesenchymal stromal cells (MSCs) of multiple origins and phenotypes are most commonly employed in the literature and mainly applied systemically in high doses in acute stroke settings, because of their nonengraftment and potent drug-like biological activity. Neural stem cells (NSCs), by contrast, are multipotent cells that are derived from developing or adult brain tissue or differentiated from pluripotent cells such as embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) in culture. These stem cells have both capacity for engraftment and neural cell differentiation as well as potent biological activity and are delivered intracerebrally in smaller volumes and cell doses; we believe that they are more suitable in patients presenting with pre-existing chronic, stable disability. Currently, there is a growing number of hNSC-derived therapies in preclinical development for ischemic stroke (Table). Leading these therapies, ReNeuron's CTX0E03 cell line (CTX) has been evaluated in a first-in-human, single-center trial in patients with moderate-to-severe disability, 6 months to 5 years after ischemic stroke9. Currently, a Phase II stroke trial in patients with upper-limb disability, 312 months poststroke is underway across multiple sites in the United Kingdom (clinicaltrials.govNCT02117635). In this review, we summarize nearly 15 years of research behind the CTX line and discuss its mode of action together with implications for therapeutic potential in stroke disability.

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Human Neural Stem Cell Therapy for Chronic Ischemic Stroke - Genetic Engineering & Biotechnology News