Laminin Alpha 2 Enhances the Protective Effect of Exosomes on Human iPSC-Derived Cardiomyocytes in an In Vitro Ischemia-Reoxygenation Model.

Ischemic heart disease, a leading cause of death worldwide, manifests clinically as myocardial infarction. Contemporary therapies using mesenchymal stromal cells (MSCs) and their derivative (exosomes, EXOs) were developed to decrease the progression of cell damage during ischemic injury. Laminin alpha 2 (LAMA2) is an important extracellular matrix protein of the heart. Here, we generated MSC-derived exosomes cultivated under LAMA2 coating to enhance human-induced pluripotent stem cell (hiPSC)-cardiomyocyte recognition of LAMA2-EXOs, thus, increasing cell protection during ischemia reoxygenation. We mapped the mRNA content of LAMA2 and gelatin-EXOs and identified 798 genes that were differentially expressed, including genes associated with cardiac muscle development and extracellular matrix organization. Cells were treated with LAMA2-EXOs 2 h before a 4 h ischemia period (1% O2, 5% CO2, glucose-free media). LAMA2-EXOs had a two-fold protective effect compared to non-treatment on plasma membrane integrity and the apoptosis activation pathway; after a 1.5 h recovery period (20% O2, 5% CO2, cardiomyocyte-enriched media), cardiomyocytes treated with LAMA2-EXOs showed faster recovery than did the control group. Although EXOs had a protective effect on endothelial cells, there was no LAMA2-enhanced protection on these cells. This is the first report of LAMA2-EXOs used to treat cardiomyocytes that underwent ischemia-reoxygenation injury. Overall, we showed that membrane-specific EXOs may help improve cardiomyocyte survival in treating ischemic cardiovascular disease.

Primary Graft Dysfunction in Lung Transplantation: A Review of Mechanisms and Future Applications.

Lung allograft recipients have worse survival than all other solid organ transplant recipients, largely because of primary graft dysfunction (PGD), a major form of acute lung injury affecting a third of lung recipients within the first 72 h after transplant. PGD is the clinical manifestation of ischemia-reperfusion injury and represents the predominate cause of early morbidity and mortality. Despite PGD's impact on lung transplant outcomes, no targeted therapies are currently available; hence, care remains supportive and largely ineffective. This review focuses on molecular and innate immune mechanisms of ischemia-reperfusion injury leading to PGD. We also discuss novel research aimed at discovering biomarkers that could better predict PGD and potential targeted interventions that may improve outcomes in lung transplantation.

Effect of intraoperative support mode on circulating inflammatory biomarkers after lung transplantation surgery.

BACKGROUND: Processes that activate the immune system during lung transplantation can lead to primary graft dysfunction (PGD) or allograft rejection. METHODS: We analyzed cytokine expression profiles after reperfusion and allograft outcomes in a cohort of patients (n = 59) who underwent lung transplantation off-pump (n = 26), with cardiopulmonary bypass (CPB; n = 18), or with extracorporeal membrane oxygenation (ECMO; n = 15). Peripheral blood was collected from patients at baseline and at 6 and 72 h after reperfusion. To adjust for clinical differences between groups, we utilized a linear mixed model with overlap weighting. RESULTS: PGD3 was present at 48 or 72 h after reperfusion in 7.7% (2/26) of off-pump cases, 20.0% (3/15) of ECMO cases, and 38.9% (7/18) of CPB cases (p = 0.04). The ECMO and CPB groups had greater reperfusion-induced increases in MIP-1B, IL-6, IL-8, IL-9, IL1-ra, TNF-alpha, RANTES, eotaxin, IP-10, and MCP-1 levels than the off-pump group. Cytokine expression profiles after reperfusion were not significantly different between ECMO and CPB groups. CONCLUSION: Our data suggest that, compared with an off-pump approach, the intraoperative use of ECMO or CPB during lung transplantation is associated with greater reperfusion-induced cytokine release and graft injury.

The Use of Natural Ingredients in the Treatment of Alopecias with an Emphasis on Central Centrifugal Cicatricial Alopecia: A Systematic Review.

BACKGROUND: Central centrifugal cicatricial alopecia (CCCA), a scarring alopecia that commonly affects women of African descent, can be challenging to manage, and there are limited treatment modalities available. The use of natural ingredients for nonscarring hair loss has gained popularity among patients, but has not been previously studied for CCCA. OBJECTIVE: We sought to review clinical studies evaluating the use of natural ingredients in the treatment of CCCA. METHODS: Systematic searches of the PubMed and SCOPUS databases were performed in March 2018 using various ingredient names and the terms alopecia, scarring alopecia, Central Centrifugal Cicatricial alopecia, and CCCA. Specific ingredients included azelaic acid, peppermint oil, pumpkin seed oil, garlic supplements/shampoo, Black castor oil, jojoba oil, argan oil, olive oil, horsetail plant oil, lavender oil, coconut oil, chamomile oil, thyme oil, tea tree oil, sulfur oil, menthol, and rosemary oil. Two reviewers independently screened titles, leading to the selection of eight clinical studies. RESULTS: A review of the literature revealed no clinical trials that evaluated the treatment of CCCA with natural ingredients. Despite limited evidence-based research for CCCA, several natural ingredients showed efficacy in alopecia areata, androgenetic alopecia, and psoriatic alopecia. CONCLUSION: Upon review of the literature, there were no randomized, controlled studies evaluating the use of natural ingredients or aromatherapy in the management of CCCA. Despite this, several botanical and natural ingredients do show promise in treating androgenetic alopecia and alopecia areata. More clinical studies need to be performed to evaluate treatment options as a whole, including natural modalities, to better serve these patients.

Blood transfusion products contain mitochondrial DNA damage-associated molecular patterns: a potential effector of transfusion-related acute lung injury.

BACKGROUND: Transfusion-related acute lung injury (TRALI) is the most frequent and severe complication in patients receiving multiple blood transfusions. Current pathogenic concepts hold that proinflammatory mediators present in transfused blood products are responsible for the initiation of TRALI, but the identity of the critical effector molecules is yet to be determined. We hypothesize that mtDNA damage-associated molecular patterns (DAMPs) are present in blood transfusion products, which may be important in the initiation of TRALI. METHODS: DNA was extracted from consecutive samples of packed red blood cells, fresh frozen plasma (FFP), and platelets procured from the local blood bank. Quantitative real-time polymerase chain reaction was used to quantify ≈200 bp sequences from the COX1, ND1, ND6, and D-loop regions of the mitochondrial genome. RESULTS: A range of mtDNA DAMPs were detected in all blood components measured, with FFP displaying the largest variation. CONCLUSIONS: We conclude that mtDNA DAMPs are present in packed red blood cells, FFP, and platelets. These observations provide proof of the concept that mtDNA DAMPs may be mediators of TRALI. Further studies are needed to test this hypothesis and to determine the origin of mtDNA DAMPs in transfused blood.