Mst1 attenuates myocardial ischemia/reperfusion injury following heterotopic heart transplantation in mice through regulating Keap1/Nrf2 axis.

Ischemia reperfusion (I/R) injury remains a frequent adverse event that accompanies heart transplantation. Oxidative stress and aberrant production of free radicals were regarded as the culprit of cell death and tissue damage in post-transplant IR injury. Mst1 has been identified as a mediator of oxidative stress and Nrf2 regulates anti-oxidative enzymes, however, the interaction between Mst1 and Nrf2 anti-oxidative stress pathway remains to be clarified in the event of cardiac IR injury.

Leflunomide Inhibits rat-to-Mouse Cardiac Xenograft Rejection by Suppressing Adaptive Immune Cell Response and NF-κB Signaling Activation.

Xenotransplantation is a potential solution for the severe shortage of human donor organs and tissues. The generation of humanized animal models attenuates strong innate immune responses, such as complement-mediated hyperacute rejection. However, acute vascular rejection and cell mediated rejection remain primary barriers to xenotransplantation, which limits its clinical application.

Vitamin D3 combined with antibody agents suppresses alloreactive memory T-cell responses to induce heart allograft long-term survival.

Background: The pre-stored memory T cells in organ transplant patient carry a high risk of allograft rejection. The current study aimed to determine whether the allogenic response of adoptively transferred memory T cells in mice was suppressed by vitamin D3 monotherapy alone or in combination with monoclonal antibody treatment.

Methods: Prior to vascularized heterotopic heart transplantation, naïve C57BL/6 mice were primed with memory T cells.

β-catenin regulates myocardial ischemia/reperfusion injury following heterotopic heart transplantation in mice by modulating PTEN pathways.

Ischemia reperfusion (I/R) injury, an inevitable event accompanying heart transplantation, is the primary factor leading to organ failure and graft rejection. In order to prevent I/R injury, we established murine heart transplantation model with I/R and cell culture system to determine whether β-catenin is a mediate factor in preventing I/R injury in heart transplantation. After successfully established heterotopic heart transplantation mice model, the I/R injury was induced, and two dynamic temporal were studied during different I/R phases.

Optimization of the Cuff Technique for Murine Heart Transplantation.

Murine cardiac transplantation has been performed for more than 40 years. With advancements in microsurgery, certain new techniques have been used to improve surgical efficiency. In our lab, we have optimized the cuff technique with two major steps.

Live birth after cervical ectopic uterus transplantation in mice.

An ideal animal model is a prerequisite for the basic research of uterus transplantation. This study aimed to develop a new cervical ectopic uterus transplantation mice model, which was established by vascular anastomosis of the right common iliac artery and vein of the donor with the right common carotid artery and external jugular vein of the recipient, respectively, using the cuff method. The survival status of the transplanted uterus was assessed by macroscopic observation and histological examination after surgery, and the function of the graft uterus was tested by verifying whether the pregnancy is possible.

Combined treatment with vitamin D3 and antibody agents suppresses secondary heart transplant rejection in the early postoperative period.

Background: Accelerated transplant rejection mediated by donor reactive memory T cells is another barrier to the induction of graft tolerance. The aim of this study was to investigate the immunosuppressing effects of vitamin D (1,25(OH)2D3), administered alone or in combination with a costimulatory blockade treatment, on rejection of secondary heart allografts in a mouse model.

Methods: Circular full-thickness skin grafts from BALB/c mice were cut and grafted onto the lumbar regions of C57BL/6 mice as allo-primed recipients.

Generation of bioartificial hearts using decellularized scaffolds and mixed cells.

Background: Patients with end-stage heart failure must receive treatment to recover cardiac function, and the current primary therapy, heart transplantation, is plagued by the limited supply of donor hearts. Bioengineered artificial hearts generated by seeding of cells on decellularized scaffolds have been suggested as an alternative source for transplantation. This study aimed to develop a tissue-engineered heart with lower immunogenicity and functional similarity to a physiological heart that can be used for heart transplantation.

Immunogenicity analysis of decellularized cardiac scaffolds after transplantation into rats.

Cardiac extracellular matrix (cECM) scaffolds are promising biomaterials for clinical applications. Our aim is to determine the immunogenicity of decellularized scaffolds from different sources for use as artificial organs during organ transplantation. We transplanted Lewis rats with syngeneic (Lewis rat cECM), allogeneic (BN rat cECM) or xenogeneic (hamster cECM) decellularized cardiac scaffolds.

A highly reproducible cervical cuff technique for rat-to-mouse heterotopic heart xenotransplantation.

Xenotransplantation is an effective way to solve the problem of donor shortage in clinical transplantation. However, clinical use of xenotransplantation is currently limited due to immunological challenges such as acute vascular rejection and cell-mediated rejection. To finally surpass this immunological barrier, more preclinical research is needed into the molecular mechanisms of rejection and the possible effects of new immunosuppressants.

Thoracoscopic anatomic pulmonary segmentectomy: a 3-dimensional guided imaging system for lung operations.

Objectives: To evaluate the Lung Operation Three-dimensional Imaging System software by Xiamen TRONG Technology Co. Ltd in detecting the precise position of solitary pulmonary nodules or ground-glass opacity nodules before surgery.

Methods: Chest, arterial phase, portal venous phase, enhanced and delayed-phase images of 10 cases with 12 nodules were obtained with a Toshiba Aquilion One 320 computed tomography (CT) scanner.

Anti-CD44 monoclonal antibody inhibits heart transplant rejection mediated by alloantigen-primed CD4(+) memory T cells in nude mice.

Donor-reactive CD4(+)memory T cells threaten the survival of transplanted organs. In this study, we used anti-CD44 monoclonal antibody (mAb) to inhibit adoptively transferred B6-reactive CD4(+)memory T cells (BALB/c origin) and to induce tolerance of B6 hearts in nude mice. The median survival time (MST) of the grafts was 6 days in the isotype group, and more than 100 days in the group treated with 8 doses of anti-CD44 at four-day intervals.

Suppressing memory T cell activation induces islet allograft tolerance in alloantigen-primed mice.

Memory T cells are known to play a key role in prevention of allograft tolerance in alloantigen-primed mice. Here, we used an adoptively transferred memory T cell model and an alloantigen-primed model to evaluate the abilities of different combinations of monoclonal antibodies (mAb) to block key signaling pathways involved in activation of effector and memory T cells. In the adoptively transferred model, the use of anti-CD134L mAb effectively prevented activation of CD4(+) memory T cells and significantly prolonged islet survival, similar to the action of anti-CD122 mAb to CD8(+) memory T cells.

The recall alloresponse following retransplantation is more intense compared with the T cell memory-transfer model.

The presence of alloreactive memory T cells in recipient is a critical handicap to achieving transplantation tolerance. To make a mouse model that can as closely as possible mimic the presensitized transplant patient is important for research on this subject. Thus, we developed a novel retransplant model and compared the alloresponse in this model with that in the memory T cells-transfer model (transfer control).

Combined costimulation blockade inhibits accelerated rejection mediated by alloantigen-primed memory T cells in mice.

Donor-reactive memory T cells threaten the survival of transplanted organs via multiple pathways. This study was undertaken to induce tolerance of cardiac allografts in mice, in which alloreactive memory T cells were adoptively transferred, by combined costimulatory blockade of both effector and memory T cells. We found that the median survival time (MST) of the grafts was 5.

Synergistic effects of Isatis tinctoria L. and tacrolimus in the prevention of acute heart rejection in mice.

Although immunosuppressive treatments are available for acute cardiac rejection no viable treatment exists for long-term cardiac graft failure. Moreover, the extended use of calcineurin inhibitor immunosuppressants, the mainstay of current treatment for cardiac transplantation, leads to significant side effects such as nephrotoxicity and an increased risk of cardiac disease. Because some agents used in Traditional Chinese Medicine (TCM) have strong immunosuppressive effects coupled with low toxicity, we investigated the effect of Compound K (K), the synthesized analogue of highly unsaturated fatty acids from Isatis tinctoria L.

Rapamycin or tacrolimus alone fails to resist cardiac allograft accelerated rejection mediated by alloreactive CD4(+) memory T cells in mice.

Donor-reactive memory T (Tm) cells undermine transplanted organs more readily than naive T cells. Rapamycin (RAPA) and tacrolimus (FK-506) are current mainstay immunosuppressants used for preventing acute allograft rejection. Although their efficacy in suppressing naive T cell is established, their suppressing effect on memory T cells is undefined.