Molecular characterization of cell types using single-cell transcriptome sequencing is revolutionizing cell biology and enabling new insights into the physiology of human organs. We created a human reference atlas comprising nearly 500,000 cells from 24 different tissues and organs, many from the same donor. This atlas enabled molecular characterization of more than 400 cell types, their distribution across tissues, and tissue-specific variation in gene expression. Using multiple tissues from a single donor enabled identification of the clonal distribution of T cells between tissues, identification of the tissue-specific mutation rate in B cells, and analysis of the cell cycle state and proliferative potential of shared cell types across tissues. Cell type–specific RNA splicing was discovered and analyzed across tissues within an individual.
Objective To report the long-term outcomes of 1218 organs transplanted from donation after cardiac death (DCD) donors from January 1980 through December 2008. Methods One-thousand two-hundred-eighteen organs were transplanted into 1137 recipients from 577 DCD donors. This includes 1038 kidneys (RTX), 87 livers (LTX), 72 pancreas (PTX), and 21 DCD lungs. The outcomes were compared with 3470 RTX, 1157 LTX, 903 PTX, and 409 lung transplants from donors after brain death (DBD). Results Both patient and graft survival is comparable between DBD and DCD transplant recipients for kidney, pancreas, and lung after 1, 3, and 10 years. Our findings reveal a significant difference for patient and graft survival of DCD livers at each of these time points. In contrast to the overall kidney transplant experience, the most recent 16-year period (n = 396 DCD and 1,937 DBD) revealed no difference in patient and graft survival, rejection rates, or surgical complications but delayed graft function was higher (44.7% vs 22.0%; P < .001). In DCD LTX, biliary complications (51% vs 33.4%; P < .01) and retransplantation for ischemic cholangiopathy (13.9% vs 0.2%; P < .01) were increased. PTX recipients had no difference in surgical complications, rejection, and hemoglobin A1c levels. Surgical complications were equivalent between DCD and DBD lung recipients. Conclusion This series represents the largest single center experience with more than 1000 DCD transplants and given the critical demand for organs, demonstrates successful kidney, pancreas, liver, and lung allografts from DCD donors. (Surgery 2011;150:692-702.)
Secretory phospholipase A 2 (sPLA 2 ) type IIa, elevated in inflammation, breaks down membrane phospholipids and generates arachidonic acid. We hypothesized that sPLA 2 will hydrolyze red blood cells that expose phosphatidylserine (PS) and generate lysophosphatidic acid (LPA) from phosphatidic acid that is elevated in PS-exposing red blood cells. In turn, LPA, a powerful lipid mediator, could affect vascular endothelial cell function. Although normal red blood cells were not affected by sPLA 2 , at levels of sPLA 2 observed under inflammatory conditions (100 ng/ml) PS-exposing red blood cells hemolyzed and generated LPA (1.2 nM/10 8 RBC). When endothelial cell monolayers were incubated in vitro with LPA, a loss of confluence was noted. Moreover, a dose-dependent increase in hydraulic conductivity was identified in rat mesenteric venules in vivo with 5 M LPA, and the combination of PS-exposing red blood cells with PLA 2 caused a similar increase in permeability. In the presence of N-palmitoyl L-serine phosphoric acid, a competitive inhibitor for the endothelial LPA receptor, loss of confluence in vitro and the hydraulic permeability caused by 5 M LPA in vivo were abolished. The present study demonstrates that increased sPLA 2 activity in inflammation in the presence of cells that have lost their membrane phospholipid asymmetry can lead to LPA-mediated endothelial dysfunction and loss of vascular integrity.Secretory phospholipase A 2 (sPLA 2 ) 2 type IIa is a low molecular weight, ubiquitous enzyme that is elevated in inflammation. The enzyme generates arachidonic acid from phospholipids for the generation of thromboxanes and leukotrienes and, as such, acts as an essential mediator in the inflammatory pathways (1). The specific membranes targeted by the enzyme for the generation of arachidonic acid during inflammation have not been clearly defined. Secretory PLA 2 has a strong preference for phospholipids that are negatively charged at physiologic pH: phosphatidylserine (PS) and phosphatidylethanolamine (PE) (2). In normal mammalian cells, these phospholipids are mainly (PE) or exclusively (PS) confined to the inner layer of the plasma membrane (1-3). Loss of this asymmetric distribution and exposure of PS on the external surface generates a thrombogenic surface and signals macrophages to remove cells by phagocytosis (1-5). Although normal mammalian cells do not seem to act as targets for sPLA 2 , loss of phospholipid asymmetry in plasma membranes and the exposure of PS have been shown to render them vulnerable to phospholipid hydrolysis (1). In addition, it has been well established that bacterial membranes are excellent substrates for this enzyme (6). Together, membranes with altered phospholipid packing are potential targets for sPLA 2 type IIa.We have previously shown that sPLA 2 is elevated after injury, predicts hypoxemia, and is related to multiorgan failure (7,8). In addition, elevated levels of sPLA 2 predict the onset of the acute chest syndrome in sickle cell disease (9 -11), the severe lung damage that...
Although guidance documents have been published regarding organ donation from individuals with a prior history of COVID‐19 infection, no data exist regarding successful recovery and transplantation from deceased donors with a history of or positive testing suggesting a prior SARS‐CoV‐2 infection. Here, we report a case series of six deceased donors with a history of COVID‐19 from whom 13 organs were recovered and transplanted through several of the nation's organ procurement organizations (OPOs). In addition, at least two potential donors were authorized for donation but with no organs were successfully allocated and did not proceed to recovery. No transmission of SARS‐CoV‐2 was reported from the six donors to recipients, procurement teams, or hospital personnel. Although more studies are needed, organ donation from deceased donors who have recovered from COVID‐19 should be considered.
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