Mitochondrial Transfer via Tunneling Nanotubes (TNT) is an Important Mechanism by which Mesenchymal Stem Cells Enhance Macrophage Phagocytosis in the in vitro and in vivo Models of ARDS

Mesenchymal stromal cells (MSC) have been reported to improve bacterial clearance in pre-clinical models of Acute Respiratory Distress Syndrome (ARDS) and sepsis. The mechanism of this effect is not fully elucidated yet. The primary objective of this study was to investigate the hypothesis that the anti-microbial effect of MSC in vivo depends on their modulation of macrophage phagocytic activity which occurs through mitochondrial transfer. We established that selective depletion of alveolar macrophages (AM) with intranasal (IN) administration of liposomal clodronate resulted in complete abrogation of MSC anti-microbial effect in the in vivo model of E.coli pneumonia. Furthermore, we showed that MSC administration was associated with enhanced AM phagocytosis in vivo. We showed that direct co-culture of MSC with monocyte-derived macrophages (MDMs) enhanced their phagocytic capacity. By fluorescent imaging and flow cytometry we demonstrated extensive mitochondrial transfer from MSC to macrophages which occurred at least partially through TNT-like structures. We also detected that lung macrophages readily acquire MSC mitochondria in vivo, and macrophages which are positive for MSC mitochondria display more pronounced phagocytic activity. Finally, partial inhibition of mitochondrial transfer through blockage of TNT formation by MSC resulted in failure to improve macrophage bioenergetics and complete abrogation of the MSC effect on macrophage phagocytosis in vitro and the anti-microbial effect of MSC in vivo.

Collectively, this work for the first time demonstrates that mitochondrial transfer from MSC to innate immune cells leads to enhancement in phagocytic activity and reveals an important novel mechanism for the anti-microbial effect of MSC in ARDS.

An investigation of IAQ, thermal comfort and Sick Building Syndrome symptoms in UK energy efficient homes

Purpose
– Concern of the deterioration of indoor environmental quality as a result of energy efficient building design strategies is growing. Apprehensions of the effect of airtight, super insulated envelopes, the reduction of infiltration, and the reliance on mechanical systems to provide adequate ventilation (air supply) is promoting emerging new research in this field. The purpose of this paper is to present the results of an indoor air quality (IAQ) and thermal comfort investigation in UK energy efficient homes, through a case study investigation.

Design/methodology/approach
– The case study dwellings consisted of a row of six new-build homes which utilize mechanical ventilation with heat recovery (MVHR) systems, are built to an average airtightness of 2m3/m2/hr at 50 Pascal’s, and constructed without a central heating system. Physical IAQ measurements and occupant interviews were conducted during the summer and winter months over a 24-hour period, to gain information on occupant activities, perception of the interior environment, building-related health and building use.

Findings
– The results suggest inadequate IAQ and perceived thermal comfort, insufficient use of purge ventilation, presence of fungal growth, significant variances in heating patterns, occurrence of sick building syndrome symptoms and issues with the MVHR system.

Practical implications
– The findings will provide relevant data on the applicability of airtight, mechanically ventilated homes in a UK climate, with particular reference to IAQ.

Originality/value
– IAQ data of this nature is essentially lacking, particularly in the UK context. The findings will aid the development of effective sustainable design strategies that are appropriate to localized climatic conditions and sensitive to the health of building occupants.

Acute Respiratory Distress Syndrome

Acute respiratory distress syndrome presents as hypoxia and bilateral pulmonary infiltrates on chest imaging in the absence of heart failure sufficient to account for this clinical state. Management is largely supportive, and is focused on protective mechanical ventilation and the avoidance of fluid overload. Patients with severe hypoxaemia can be managed with early short-term use of neuromuscular blockade, prone position ventilation, or extracorporeal membrane oxygenation. The use of inhaled nitric oxide is rarely indicated and both β2 agonists and late corticosteroids should be avoided. Mortality remains at approximately 30%.