Hydrogels for neuroprotection and functional rewiring: a new era for brain engineering

The neurological devastation of neurodegenerative and cerebrovascular diseases reinforces our perseverance to find advanced treatments to deal with these fatal pathologies.High-performance preclinical results have failed at clinical level,as it has been the case for a wide variety of neuroprotective agents and cell-based therapies employed to treat high prevalent brain pathologies such as stroke,Alzheimer’s and Parkinson’s diseases.An unquestionable reality is the current absence of effective therapies to neuroprotect the brain,to arrest neurodegeneration and rewire the impaired brain circuits.Part of the problem might arise from the lack of adequate in vitro and in vivo models and that most of the underlying pathophysiological mechanisms are not yet clarified.Another contributing factor is the lack of efficient systems to sustain drug release at therapeutic concentrations and enhance the survival and function of grafted cells in transplantation procedures.For medical applications the use of biomaterials of different compositions and formats has experienced a boom in the last decades.Although the greater complexity of central nervous system has probably conditioned their extensive use with respect to other organs,the number of biomaterials-based applications to treat the injured brain or in the process of being damaged has grown exponentially.Hydrogel-based biomaterials have constituted a turning point in the treatment of cerebral disorders using a new form of advanced therapy.Hydrogels show mechanical properties in the range of cerebral tissue resulting very suitable for local implantation of drugs and cells.It is also possible to fabricate three-dimensional hydrogel constructs with adaptable mesh size to facilitate axonal guidance and elongation.Along this article,we review the current trends in this area highlighting the positive impact of hydrogel-based biomaterials over the exhaustive control of drug delivery,cell engraftment and axonal reinnervation in brain pathologies.     

Photoreceptor plasticity in reaggregates of embryonic chick retina: rods depend on proximal cones and on tissue organization

Plasticity of photoreceptors and their integration into epithelial structures homologous to an outer nuclear layer (ONL), was investigated in embryonic chick retinal cell reaggregates by immunohistochemistry using an antibody specific for red plus green cones (RG-cones) and an antibody for rods. If reaggregates are raised in the presence of pigmented epithelium (RPE), completely reconstructed, stratified retinal spheres are produced, where all rods and cones are integrated into an outer laminar ONL, similar to a normal retina. In the absence of RPE, 'rosetted' spheres form which contain internal rosettes homologous to an ONL. Only a minor fraction of cones and rods of 'rosetted' spheres are located within rosettes, while a larger fraction is diffusely displaced in nonorganized areas, thus, not contributing to an ONL-like epithelium. In both types of spheres, the total percentage of RG-cones was similar to the in vivo retina, indicating that expression of cones is autonomous. Following cones, after about one day, rods developed only within already existing RG-cone clusters. Thereby, the ratio of rods to RG-cones increases as the tissue organization decreases: for stratified spheres this ratio is, 0.50 (1 rod/2 cones; similar to mature retina); for rosettes, 0.74 (3 rods/4 cones) and for nonorganized areas, 1.09 (1 rod/1 cone) -- a higher ratio under our conditions has never been detected. Thus, rod expression depends strictly on the presence of nearby cones; their relative numbers are distinctively adjusted according to the cytoarchitecture of the tissue environment. The biomedical implications of these findings are briefly discussed.     

Stem cell transplantation for treating Parkinson's disease Literature analysis based on the Web of Science

OBJECTIVE:To identify global research trends of stem cell transplantation for treating Parkinson’s disease using a bibliometric analysis of the Web of Science.DATA RETRIEVAL:We performed a bibliometric analysis of data retrievals for stem cell transplantation for treating Parkinson’s disease from 2002 to 2011 using the Web of Science.SELECTION CRITERIA:Inclusion criteria:(a) peer-reviewed articles on stem cell transplantation for treating Parkinson’s disease which were published and indexed in the Web of Science;(b) type of articles:original research articles,reviews,meeting abstracts,proceedings papers,book chapters,editorial material and news items;(c) year of publication:2002-2011.Exclusion criteria:(a) articles that required manual searching or telephone access;(b) we excluded documents that were not published in the public domain;(c) we excluded a number of corrected papers from the total number of articles.MAIN OUTCOME MEASURES:(1) Type of literature;(2) annual publication output;(3) distribution according to journals;(4) distribution according to subject areas;(5) distribution according to country;(6) distribution according to institution;(7) comparison of countries that published the most papers on stem cell transplantation from different cell sources for treating Parkinson’s disease;(8) comparison of institutions that published the most papers on stem cell transplantation from different cell sources for treating Parkinson’s disease in the Web of Science from 2002 to 2011;(9) comparison of studies on stem cell transplantation from different cell sources for treating Parkinson’s disease RESULTS:In total,1 062 studies on stem cell transplantation for treating Parkinson’s disease appeared in the Web of Science from 2002 to 2011,almost one third of which were from American authors and institutes.The number of studies on stem cell transplantation for treating Parkinson’s disease had gradually increased over the past 10 years.Papers on stem cell transplantation for treating Parkinson’s disease appeared in journals such as Stem Cells and Experimental Neurology.Although the United States published more articles addressing neural stem cell and embryonic stem cell transplantation for treating Parkinson’s disease,China ranked first for articles published on bone marrow mesenchymal stem cell transplantation for treating Parkinson’s disease.CONCLUSION:From our analysis of the literature and research trends,we found that stem cell transplantation for treating Parkinson’s disease may offer further benefits in regenerative medicine.     

A phase 1 study of prasugrel in patients with sickle cell disease: Effects on biomarkers of platelet activation and coagulation

Introduction

Prasugrel, a P2Y₁₂ adenosine diphosphate (ADP) receptor antagonist effectively inhibits ADP-mediated platelet activation and aggregation, and may be useful in reducing vaso-occlusive crises in sickle cell disease (SCD). In this study, we assess the effect of prasugrel on biomarkers of platelet activation and coagulation in patients with SCD.

Materials and Methods

Twelve adult patients with SCD and 13 healthy subjects were examined before and after 12 ± 2 days of 5.0 or 7.5 mg/day oral prasugrel. Assessed cellular biomarkers included monocyte- and neutrophil-platelet aggregates, activated glycoprotein IIb-IIIa (GPIIbIIIa), P-selectin, CD40 ligand (CD40L), tissue factor (TF) expression on circulating platelets and on monocyte-platelet aggregates, and platelet-erythrocyte aggregates. Soluble biomarkers included CD40L, prothrombin fragment 1.2 (F1.2), thromboxane B₂ (TXB₂), P-selectin, and TF.

Results

Patients with SCD had increased platelet baseline activation compared to healthy subjects, as measured by percentages of monocyte-platelet aggregates, neutrophil-platelet aggregates, and platelets expressing CD40L. Likewise, baseline levels of soluble F1.2 and TXB₂ were elevated in patients with SCD compared to healthy subjects. After 12 days of prasugrel, patients with SCD had a significant reduction in platelet-monocyte aggregates that was not observed in healthy subjects. Following prasugrel administration, those with SCD maintained higher levels of monocyte-platelet aggregates and soluble F1.2, but had lower levels of platelet-erythrocyte aggregates and soluble TF compared to healthy subjects.

Conclusions

These results provide evidence for chronic platelet activation in the SCD steady state, activation that was in part attenuated by prasugrel, thereby suggesting that ADP may mediate platelet activation in SCD.