ABSTRACT
Objective To investigate the application prospect of the most extensive genome engineering pig internationally in preclinical xenotransplantation. Methods Porcine endogenous retrovirus (PERV) knockout combined with 3 major heterologous antigen gene knockouts and 9 humanized genes for inhibition of complement activation, regulation of coagulation disorders, anti-inflammatory and anti-phagocytosis were transferred into a pig (PERV-KO/3-KO/9-TG) as a donor, and the heart, liver and kidney were obtained and transplanted to 3 Rhesus macaque recipients respectively to establish a preclinical research model of pig-to-Rhesus macaque xenotransplantation. The functional status of xenografts after blood flow reconstruction was observed and the survival of recipients was summarized. The hemodynamics of xenografts were monitored. The change of hematological indexes of each recipient was compared. The histopathological manifestation of xenografts was observed. Results After the blood flow was reconstructed, all xenografts showed ruddy color, soft texture and good perfusion. The transplant heart, liver and kidney showed full arterial and venous blood flow and good perfusion at 1 d after operation. The postoperative survival time of heart, liver, and kidney transplant recipients was 7, 26, and 1 d, respectively. The levels of creatine kinase, creatine kinase isoenzyme, and lactate dehydrogenase increased in heart transplant recipient at 1 d after operation, and gradually recovered to near normal levels at 6 d after operation. All indexes increased sharply at 7 d after operation. The level of aspartate aminotransferase increased in liver transplant recipients at 2 d after operation, and the alanine aminotransferase basically returned to normal at 10 d after operation, but the total bilirubin continued to increase. Both aspartate aminotransferase and alanine aminotransferase increased at 12 d after operation, and reached a peak at 15 d after operation. The kidney transplant recipient developed mild proteinuria at 1 d after operation, and died of sudden severe arrhythmia. Histopathology showed that the tissue structure of cardiac and renal xenografts was close to normal, and liver xenografts presented with patchy necrosis, the liver tissue structure was disordered, accompanied by inflammatory damage, interstitial hemorrhage and thrombotic microangiopathy. Conclusions PERV-KO/3-KO/9-TG pig shows advantages in overcoming hyperacute rejection, mitigating humoral rejection and coagulation dysregulation. However, whether it can be used as potential donor for clinical xenotransplantation needs further evaluation.
ABSTRACT
Objective To explore the effects of different body positions at the expiratory phase thinsection multi-slice spiral CT on the diagnosis of pulmonary air trapping after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods Thirty-one allo-HSCT patients underwent the expiratory phase low-dose MSCT lung scanning at supine and prone positions to detect whether they have air trapping lesion,the volume percent of air trapping region (CT value ≤-700 HU at expiratory phase) against the whole lung was measured by using GE workstation after grading.Statistical analysis on lesion detection rate was performed with McNemar test and volume percent with rank sum test.Results Air trapping regions were observed in 8 patients (25.8％,8/31) who performed CT scan at the supine position,while 15 cases (48.4％,15/31)were positive for prone position CT scan.Seven cases showed positive results at both body positions.Statistical significance in the positive detection rate at supine and prone positions was found (x2 =4.00,P =0.039).The volume fraction of the two positions was 13 for supine position and 21 for prone position with statistical significance (Z =-3.37,P =0.001).Sensitivity at prone position CT scan to detect air trapping was much higher than that at supine position CT scan.Conclusion For allo-HSCT patients with chronic rejection reaction,performing expiratory phase thin-section CT scan and prone position scan can not only improve the detection rate of lung forepart lesions,but also preliminarily evaluate the severity of the air trapping,which can provide a basis for the early diagnosis and treatment in clinics.