Stroke is the second leading cause of death in the world population. Stroke affects approximately 6 million people in the European Union, with 1.1 million new cases every year. When not fatal, despite spontaneous recovery, stroke often results in disability (70% of stroke survivors), due to motor and/or cognitive impairments, and secondary health problems affecting not only patients but also their families.
Current treatment options are limited to intravenous thrombolysis, thrombectomy, aspirin, decompressive craniectomy, and management in stroke care units for intensive care and rehabilitation. Effective treatments beyond prevention and acute care are urgently needed. This requires a sophisticated understanding of stroke pathophysiology. It is well-known that stroke effects are not limited to neurons but involve both brain cells and the surrounding extracellular matrix in a “glio-neurovascular niche” that interacts with the peripheral immune system. For these reasons, new therapies should target all these systems rather than narrowly targeting an individual damage process. A promising approach for treatment of stroke is activation of brain repair mechanisms and enhancement of spontaneous functional recovery. The major advantage of cell-based therapies is the extended therapeutic time window up to several weeks or months after the initial insult. This makes the treatment available to a much larger number of stroke patients. Cell-based restorative therapies have emerged as attractive approaches for the treatment of stroke. Transplanted cells, an example of “plastic” biological products, can adapt to different local conditions in damaged brain tissue while not being limited to a unique target. They can act on a wide range of endogenous protective and brain repair processes including immunomodulation, neuronal, vascular and glial remodelling.
Building on emerging preclinical and pilot clinical evidences, RESSTORE project focuses on the clinical assessment of reparative cell therapy to improve stroke recovery and patients’ quality of life. RESSTORE European multicentre randomised trial will explore, for the first time, the safety and efficacy (functional recovery) of intravenous infusion of allogenic adipose tissue derived stem cells (ADSCs) in stroke patients. Therapeutic effects of ADSCs will be assessed in patients using clinical rating scales, multimodal MRI and novel blood biomarkers. Additionally, the societal value and cost-effectiveness of ADSCs-based therapy will be evaluated through health economics and predictive in silico simulations.
Complementary ancillary animal studies support the clinical trial by defining i) if the treatment response can be further enhanced by intensive rehabilitation, ii) the contribution of co-morbidities (diabetes, hypertension) and iii) the mechanism(s) underlying the therapeutic effect.
The European regenerative therapy capacities (France, Spain, Finland, UK and Czech Republic), developed in RESSTORE cover the full value chain: large scale GMP cell production, clinical testing, biomarkers discovery, understanding of the repair mechanisms, modelling, biobanking, economic studies, exploitation and communication plan.
