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Stem cell therapies have shown promise in promoting recovery in stroke but have been limited by poor cell survival and differentiation. We have developed a hyaluronic acid (HA)-based self-polymerizing hydrogel that serves as a platform for adhesion of structural motifs and a depot release for growth factors to promote transplant stem cell survival and differentiation. We took an iterative approach in optimizing the complex combination of mechanical, biochemical and biological properties of an HA cell scaffold. First, we optimized stiffness for a minimal reaction of adjacent brain to the transplant. Next hydrogel crosslinkers sensitive to matrix metalloproteinases (MMP) were incorporated as they promoted vascularization. Finally, candidate adhesion motifs and growth factors were systemically changed in vitro using a design of experiment approach to optimize stem cell survival or proliferation. The optimized HA hydrogel, tested in vivo, promoted survival of encapsulated human neural progenitor cells (iPS-NPCs) after transplantation into the stroke core and differentially tuned transplanted cell fate through the promotion of glial, neuronal or immature/progenitor states. This HA hydrogel can be tracked in vivo with MRI. A hydrogel can serve as a therapeutic adjunct in a stem cell therapy through selective control of stem cell survival and differentiation in vivo., (Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Stroke disability is the only major disease without an effective treatment. The substantial clinical burden of stroke in disabled survivors and the lack of a medical therapy that promotes recovery provide an opportunity to explore the use of biomaterials to promote brain repair after stroke. Hydrogels can be injected as a liquid and solidify in situ to form a gelatinous solid with similar mechanical properties to the brain. These biomaterials have been recently explored to generate pro-repair environments within the damaged organ. This review highlights the clinical problem of stroke treatment and discusses recent advances in using in situ forming hydrogels for brain repair., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Gross albuminuria is associated with increased stroke risk, but it is unclear whether stroke incidence varies by level of albuminuria. We meta-analyzed prospective cohort studies to investigate the impact of various albuminuria levels and continuous urinary albumin excretion (UAE) change on stroke risk., Methods: Systematic search for studies reporting quantitative estimates of the multivariate-adjusted relative risk (RR) and 95% CI for stroke risk associated with microalbuminuria (UAE 30-300 mg/day or nearest equivalent interval) and macroalbuminuria (UAE >300 mg/day) and studies that analyzed the relation of stroke with UAE continuously. Estimates were combined using a random-effect model., Results: We identified seven studies comprising 46,638 participants with 1,479 stroke events. Incident stroke risk was greater for macroalbuminuria (RR 2.65, 95% CI 2.25-3.14) than microalbuminuria (RR 1.58, 95% CI 1.39-1.80), a difference that was significant (p for heterogeneity < 0.001, I(2) = 96%). In addition, risk of stroke increased proportionally with rising UAE (p < 0.001), even for UAE within normal range (beginning from levels as low as 2-4 mg/g)., Conclusions: Higher albuminuria level confers greater stroke risk. These findings provide additional weight to evidence that albuminuria is strongly linked to stroke risk, and suggest that persons with elevated UAE levels may especially benefit from more intensive vascular risk reduction., (Copyright © 2010 S. Karger AG, Basel.)