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Summary: Mesenchymal stem cells (MSCs) are being studied for the treatment of COVID-19-associated critical illness, due to their immunomodulatory properties. Here, we hypothesized that viral mimic-priming improves MSCs’ abilities to rebalance the dysregulated immune responses in COVID-19. Transcriptome analysis of poly(I:C)-primed MSCs (pIC-MSCs) showed upregulation of pathways in antiviral and immunomodulatory responses. Together with increased expression of antiviral proteins such as MX1, IFITM3, and OAS1, these changes translated to greater effector functions in regulating monocytes and granulocytes while further enhancing MSCs’ ability to block SARS-CoV-2 pseudovirus entry into epithelial cells. Most importantly, the addition of pIC-MSCs to COVID-19 patient whole blood significantly reduced inflammatory neutrophils and increased M2 monocytes while enhancing their phagocytic effector function. We reveal for the first time that MSCs can be primed by Toll-like receptor 3 agonist to improve their ability to rebalance the dysregulated immune responses seen in severe SARS-CoV-2 infection.

Background: Characterization of the mesenchymal stromal cell (MSC) safety profile is important as this novel therapy continues to be evaluated in clinical trials for various inflammatory conditions. Due to an increase in published randomized controlled trials (RCTs) from 2012–2019, we performed an updated systematic review to further characterize the MSC safety profile. Methods: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and Web of Science (to May 2018) were searched. RCTs that compared intravascular delivery of MSCs to controls in adult populations were included. Pre-specified adverse events were grouped according to: (1) immediate, (2) infection, (3) thrombotic/embolic, and (4) longer-term events (mortality, malignancy). Adverse events were pooled and meta-analyzed by fitting inverse-variance binary random effects models. Primary and secondary clinical efficacy endpoints were summarized descriptively. Findings: 7473 citations were reviewed and 55 studies met inclusion criteria (n = 2696 patients). MSCs as compared to controls were associated with an increased risk of fever (Relative Risk (RR) = 2·48, 95% Confidence Interval (CI) = 1·27–4·86; I2 = 0%), but not non-fever acute infusional toxicity, infection, thrombotic/embolic events, death, or malignancy (RR = 1·16, 0·99, 1·14, 0·78, 0·93; 95% CI = 0·70–1·91, 0·81–1·21, 0·67–1·95, 0·65–0·94, 0·60–1·45; I2 = 0%, 0%, 0%, 0%, 0%). No included trials were ended prematurely due to safety concerns. Interpretations: MSC therapy continues to exhibit a favourable safety profile. Future trials should continue to strengthen study rigor, reporting of MSC characterization, and adverse events. Funding: Stem Cell Network, Ontario Institute for Regenerative Medicine and Ontario Research Fund Keywords: Mesenchymal stem cells, Safety, Adverse events, Systematic review

Micro-computed tomography (micro-CT) is used in pre-clinical research to generate high-resolution three-dimensional (3D) images of organs and tissues. When combined with intravascular contrast agents, micro-CT can provide 3D visualization and quantification of vascular networks in many different organs. However, the lungs present a particular challenge for contrast perfusion due to the complexity and fragile nature of the lung microcirculation. The protocol described here has been optimized to achieve consistent lung perfusion of the microvasculature to vessels

Background.: This study estimates the maximum price at which mesenchymal stem cell (MSC) therapy is deemed cost-effective for septic shock patients and identifies parameters that are most important in making treatment decisions.Methods: We developed a probabilistic Markov model according to the sepsis care trajectory to simulate costs and quality-adjusted life years (QALYs) of septic shock patients receiving either MSC therapy or usual care over their lifetime. We calculated the therapeutic headroom by multiplying the gains attributable to MSCs with willingness-to-pay (WTP) threshold and derived the maximum reimbursable price (MRP) from the expected net monetary benefit and savings attributable to MSCs. We performed scenario analyses to assess the impact of changes to assumptions on the study findings. A value of information analysis is performed to identify parameters with greatest impact on the uncertainty around the cost-effectiveness of MSC therapy.Results: At a WTP threshold of $50,000 per QALY, the therapeutic headroom and MRP of MSC therapy were $20,941 and $16,748, respectively; these estimates increased with the larger WTP values and the greater impact of MSCs on in-hospital mortality and hospital discharge rates. The parameters with greatest information value were MSC's impact on in-hospital mortality and the baseline septic shock in-hospital mortality.Conclusion: At a common WTP of $50,000/QALY, MSC therapy is deemed to be economically attractive if its unit cost does not exceed $16,748. This ceiling price can be increased to $101,450 if the therapy significantly reduces both in-hospital mortality and increases hospital discharge rates. [ABSTRACT FROM AUTHOR]

Pulmonary arterial hypertension (PAH) presents a challenging problem for health care providers, as effective long-term therapies have been elusive. An emerging paradigm for the pathogenesis of PAH is that endothelial cell injury and apoptosis at the level of the precapillary arteriole could be the initiating event in the pathogenesis of this disease. This hypothesis has spurred research on novel regenerative approaches using stem and progenitor cells. In this review, we compare findings from the latest preclinical and clinical studies using endothelial progenitor cell (EPC) and mesenchymal stem cell (MSC) therapy to treat PAH. Additionally, we highlight recent advances in geneenhanced cell therapy, an approach that promises to augment the therapeutic potential of EPCs and MSCs especially for the reversal of established PAH. These new regenerative approaches have shown great promise in preclinical studies; however, large, rigorously designed clinical studies will be necessary to establish clinical efficacy. [ABSTRACT FROM AUTHOR]

The article offers information on the self-study activity introduced by the Washington University School of Medicine in Missouri to discuss the cause and treatment of pulmonary arterial hypertension (PAH). It further informs that the activity has been organized for cardiologists, pulmonologists and rheumatologists. It mentions the faculty members attending the activity which include professors R. James White, James West and Shirley H. J. Mei.