Cellular recovery after prolonged warm ischaemia of the whole body

Andrijević, David; Vrselja, Zvonimir; Lysyy, Taras; Zhang, Shupei; Škarica, Mario; Spajic, Ana; Dellal, David; Thorn, Stephanie; Duckrow, Robert B.; Ma, Shaojie; Duy, Phan Q.; Isiktas, Atagun U.; Liang, Dan; Li, Mingfeng; Kim, Suel Kee; Daniele, Stefano G.; Banu, Khadija; Perincheri, Sudhir; Menon, Madhav C.; Hüttner, Anita; Sheth, Kevin N; Gobeske, Kevin T.; Tietjen, Gregory T.; Zaveri, Hitten P.; Latham, Stephen R.; Sinusas, Albert J.; Šestan, Nenad

doi:10.1038/s41586-022-05016-1

Cited by 61 publications

(44 citation statements)

References 66 publications

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“…To assess whether intercellular signaling is altered in ME/CFS, we used CellChat (Vu et al, 2022) to analyze scRNA-seq data to model communication between cell types as a function of ligand and receptor expression levels corresponding to established signaling pathways (Jin et al, 2021) (Figure 5A). To remove potentially confounding factors such as sex, exercise and cluster size, we focused our analysis on the larger female-only cohort at baseline and down-sampled large clusters to 500 cells before calculating communication probabilities, an approach recommended for similar analyses (Andrijevic et al, 2022). Comparing the interactomes of patient and control cells, we found widespread evidence suggesting alterations in inferred communication to and from several cell types.…”

Section: Resultsmentioning

confidence: 99%

Single-cell transcriptomics of the immune system in ME/CFS at baseline and following symptom provocation

Ahmed

Zhu

et al. 2022

Preprint

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ME/CFS is a serious and poorly understood disease. To understand immune dysregulation in ME/CFS, we used single-cell RNA-seq (scRNA-seq) to examine immune cells in cohorts of patients and controls. Post-exertional malaise (PEM), an exacerbation of symptoms following strenuous exercise, is a characteristic symptom of ME/CFS. Thus, to detect changes coincident with PEM, we also performed scRNA-seq on the same cohorts following exercise. At baseline, ME/CFS patients displayed dysregulation of classical monocytes suggestive of inappropriate differentiation and migration to tissue. We were able to identify both diseased and more normal monocytes within patients, and the fraction of diseased cells correlated with metrics of disease severity. Comparing the transcriptome at baseline and post-exercise challenge, we discovered patterns indicative of improper platelet activation in patients, with minimal changes elsewhere in the immune system. Taken together, these data identify immunological defects present at baseline in patients and an additional layer of dysregulation following exercise.

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Section: Resultsmentioning

confidence: 99%

Single-cell transcriptomics of the immune system in ME/CFS at baseline and following symptom provocation

Ahmed

Zhu

et al. 2022

Preprint

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“…Even if ischemic time reported in this work may appear prohibitive, there are several experiences showing that mammalian cells might be more resistant to ischemic damages than expected. 25 A work recently published on Nature showed that an optimized perfusion machine technology and cytoprotective perfusate has the potential to reinstate circulation while restoring acceptable physiological and metabolic parameters after prolonged ischemic time (1 h). The further implementation of ECMO technology applied to body perfusion could work as a game changer in the field of DCD grafts and oblige transplant community to re-consider the boundaries of organ donation.…”

Section: Discussionmentioning

confidence: 99%

The role of sequential normothermic regional perfusion and end‐ischemic normothermic machine perfusion in liver transplantation from very extended uncontrolled donation after cardiocirculatory death

et al. 2022

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The use of pre-procurement normothermic regional perfusion (NRP) allowed us to implement controlled DCD liver transplantation with results comparable to brain death donors, but the use of uncontrolled DCD is declining due to logistic challenges and the high incidence of post-transplant complications. In Italy, the mandatory stand-off period of 20 min for DCD donors has driven the combined use of NRP and ex-situ machine perfusion with the intent to counterbalance the negative impact of prolonged warm ischemia. Organ viability during NRP is based on duration of warm ischemia, regional perfusion flow, lactate, transaminases values and histology, and those used in Italy are the widest worldwide. However, this evaluation can be difficult, especially when the acute damage is particularly severe. The use of ex-situ NRP could provide a safe organ evaluation. In the period from 06/2020 to 06/2022, all DCD grafts exceeding NRP viability criteria at a single center were eventually evaluated using ex-situ normothermic machine perfusion. Machine perfusion viability criteria were based on lactate clearance, irrespectively to bile production, unless 1-h transaminases perfusate level were not exceeding 5000 IU/L. Three cases of uncontrolled DCD grafts in excess of NRP viability criteria underwent ex-situ graft evaluation. Two matched ex-situ normothermic machine perfusion viability criteria and were successfully transplanted.Both recipients are doing well after 26 and 5 months after surgery with no signs of ischemic cholangiopathy. This experience suggests that the sequential use of NRP and normothermic machine perfusion may further expand the boundaries of organ viability in uncontrolled DCD liver transplantation.

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“…Interestingly, when compared to conventional extracorporeal membrane oxygenation, animals treated with the novel intervention showed reduced tissue injury in the brain, liver, heart and kidney, as assessed by histology. Further, transcriptomic analysis identified enrichment of gene sets positively associated with ATP metabolism and DNA repair when the novel approach was implemented [ 66 , 67 ].…”

Section: Mitochondrial Signaling In Trauma and In Critical Diseasesmentioning

confidence: 99%

Mitochondria Drive Immune Responses in Critical Disease

Tiwari‐Heckler

Robson

Longhi

2022

Cells

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Mitochondria engage in multiple cellular and extracellular signaling pathways ranging from metabolic control, antiviral and antibacterial host defense to the modulation of inflammatory responses following cellular damage and stress. The remarkable contributions of these organelles to innate and adaptive immunity, shape cell phenotype and modulate their functions during infection, after trauma and in the setting of inflammatory disease. We review the latest knowledge of mitochondrial biology and then discuss how these organelles may impact immune cells to drive aberrant immune responses in critical disease.

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Cellular recovery after prolonged warm ischaemia of the whole body

Cited by 61 publications

References 66 publications

Single-cell transcriptomics of the immune system in ME/CFS at baseline and following symptom provocation

Single-cell transcriptomics of the immune system in ME/CFS at baseline and following symptom provocation

The role of sequential normothermic regional perfusion and end‐ischemic normothermic machine perfusion in liver transplantation from very extended uncontrolled donation after cardiocirculatory death

Mitochondria Drive Immune Responses in Critical Disease

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