The Role of Natural-Based Biomaterials in Advanced Therapies for Autoimmune Diseases

Autoimmune diseases (ADs) constitute a heterogeneous group of more than 100 pathophysiological conditions in which an immune response against the self is observed. The incidence and prevalence of these chronic diseases are increasing with inherently high social and economic impacts. The currently available therapies generally focus on reducing the activity of the immune system and, therefore, can present severe side effects such as enhanced patient susceptibility to opportunistic infections. Advanced therapies emerged as promising treatments and with real curative potential for ADs. Additionally, the use of natural polymers to engineer gene therapies, cell therapies and/or tissue-engineered medicinal products presents specific advantages. Natural polymers present higher affinity with biological systems than synthetic polymers, and frequently have a chemical structure and motifs similar to those existing in the extracellular matrix of the tissues. They also have good biological performance, making them very strong candidates for advanced therapy medicinal products. This review discusses the therapeutic advances and provides demonstrative examples of the role of natural-based biomaterials for the development of advanced therapies for ADs.Programa Operacional Norte 2020 under the research project FROnTHERA (NORTE-01-0145-FEDER-000023) and the Fundação para a Ciência e Tecnologia do Ministério da Ciência e Tecnologia (FCT, Portugal) under the research project SPARTAN (PTDC/CTM-BIO/4388/2014)info:eu-repo/semantics/publishedVersio

Elimination of substances from the brain parenchyma: efflux via perivascular pathways and via the blood-brain barrier.

This review considers efflux of substances from brain parenchyma quantified as values of clearances (CL, stated in µL g-1 min-1). Total clearance of a substance is the sum of clearance values for all available routes including perivascular pathways and the blood-brain barrier. Perivascular efflux contributes to the clearance of all water-soluble substances. Substances leaving via the perivascular routes may enter cerebrospinal fluid (CSF) or lymph. These routes are also involved in entry to the parenchyma from CSF. However, evidence demonstrating net fluid flow inwards along arteries and then outwards along veins (the glymphatic hypothesis) is still lacking. CLperivascular, that via perivascular routes, has been measured by following the fate of exogenously applied labelled tracer amounts of sucrose, inulin or serum albumin, which are not metabolized or eliminated across the blood-brain barrier. With these substances values of total CL ≅ 1 have been measured. Substances that are eliminated at least partly by other routes, i.e. across the blood-brain barrier, have higher total CL values. Substances crossing the blood-brain barrier may do so by passive, non-specific means with CLblood-brain barrier values ranging from  1000 for water and CO2. CLblood-brain barrier values for many small solutes are predictable from their oil/water partition and molecular weight. Transporters specific for glucose, lactate and many polar substrates facilitate efflux across the blood-brain barrier producing CLblood-brain barrier values > 50. The principal route for movement of Na+ and Cl- ions across the blood-brain barrier is probably paracellular through tight junctions between the brain endothelial cells producing CLblood-brain barrier values ~ 1. There are large fluxes of amino acids into and out of the brain across the blood-brain barrier but only small net fluxes have been observed suggesting substantial reuse of essential amino acids and α-ketoacids within the brain. Amyloid-β efflux, which is measurably faster than efflux of inulin, is primarily across the blood-brain barrier. Amyloid-β also leaves the brain parenchyma via perivascular efflux and this may be important as the route by which amyloid-β reaches arterial walls resulting in cerebral amyloid angiopathy