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“Lung-on-a-chip” (LoC) is a microfluidic device, imitating the gas-fluid interface of the pulmonary alveole in the human lung and intended for pathophysiological, pharmacological and molecular-biological studies of the air-blood barrier in vitro. The LoC device itself contains a system of fluid and gas microchannels, separated with a semipermeable elastic membrane, containing a polymer base and the alveolar cell elements. Depending on the type of LoC (single-, double- and three-channel), the membrane may contain only alveolocytes or alveolocytes combined with other cells — endotheliocytes, fibroblasts, alveolar macrophages or tumor cells. Some LoC models also include proteinic or hydrogel stroma, imitating the pulmonary interstitium. The first double-channel LoC variant, in which one side of the membrane contained an alveolocytic monolayer and the other side — a monolayer of endotheliocytes, was developed in 2010 by a group of scientists from the Harvard University for maximally precise in vitro reproduction of the micro-environment and biomechanics operations of the alveoli. Modern LoC modifications include the same elements and differ only by the construction of the microfluidic system, by the biomaterial of semipermeable membrane, by the composition of cellular and stromal elements and by specific tasks to be solved. Besides the LoC imitating the hematoalveolar barrier, there are modifications for studying the specific pathophysiological processes, for the screening of medicinal products, for modeling specific diseases, for example, lung cancer, chronic obstructive pulmonary disease or asthma. In the present review, we have analyzed the existing types of LoC, the biomaterials used, the methods of detecting molecular processes within the microfluidic devices and the main directions of research to be conducted using the “lung-on-a-chip”.

Ischemic stroke is a global medical problem and one of the leading causes of death or disability worldwide. The main approach of ischemic stroke therapy in the most acute period, which can prevent or minimize the development of a neurological deficit, is the restoration of the blood flow in the ischemic brain tissue using enzymatic thrombolysis or endovascular thromboextraction. When the therapeutic window is missed, the modulation of the acute inflammatory response may play an important role in determining the fate of neurons in the penumbra. The key players in this process are T-regulatory cells (Tregs) an immunosuppressive population of CD4+ T-cells with the CD4+, CD25+ CD127low, FoxP3+ phenotype. Despite the existing reports that Tregs (or certain Treg subpopulations) can exacerbate microcirculatory disorders in the ischemic tissue, many stadies convincingly suggest the positive role of Tregs in ischemic stroke. Resident CD69+ Tregs found in the normal mammalian brain have neuroprotective activity, produce IL-10 and other anti-inflammatory cytokines, control astrogliosis, and downregulate cytotoxic subpopulations of T cells and microglia. Systemic administration of Treg in stroke is accompained by a decrease in the volume of cerebral infarction and decreased levels of secondary neuronal death. Thus, the methods allowing Treg activation and expansion ex vivo open up several new avenues for the immunocorrection not only in systemic and autoimmune diseases, but, potentially, in the neuroprotective therapy for ischemic stroke. The relationship between Treg, inflammation, and cerebrovascular pathology is of particular interest in the case of ischemic stroke and COVID-19 as a comorbidity. It has been demonstrated that systemic inflammation caused by SARS-CoV-2 infection leads to a significant suppression of Treg, which is accompanied by an increased risk for the development of ischemic stroke and other neurological complications. Overall, the information summarized herein about the possible therapeutic potential of Treg in cerebrovascular pathology may be of practical interest not only for researchers, but also for clinicians.