Timing of Mesenchymal Stromal Cell Therapy Defines its Immunosuppressive Effects in a Rat Lung Transplantation Model.

Cell therapy using mesenchymal stromal cells (MSCs) is being studied for its immunosuppressive effects. In organ transplantation, the amount of MSCs that accumulate in transplanted organs and other organs may differ depending on administration timing, which may impact their immunosuppressive effects. , adipose-derived mesenchymal stem cells (ADMSCs) suppress lymphocyte activation under cell-to-cell contact conditions.

Adipose-Derived Mesenchymal Stem Cells Attenuate Immune Reactions Against Pig Decellularized Bronchi Engrafted into Rat Tracheal Defects.

Decellularized scaffolds are promising biomaterials for tissue and organ reconstruction; however, strategies to effectively suppress the host immune responses toward these implants, particularly those without chemical crosslinking, remain warranted. Administration of mesenchymal stem cells is effective against immune-mediated inflammatory disorders. Herein, we investigated the effect of isogeneic abdominal adipose-derived mesenchymal stem/stromal cells (ADMSCs) on xenogeneic biomaterial-induced immunoreactions.

Donor and Recipient Adipose-Derived Mesenchymal Stem Cell Therapy for Rat Lung Transplantation.

Background: Mesenchymal stem cells (MSCs) are beginning to be proven as immunosuppressant in the field of organ transplantation. However, the effects of MSC origin (donor or recipient) on immunosuppression are not clear. Hence, we investigated the effects of recipient and donor adipose-derived MSCs (ADMSCs) on immunosuppression in a rat lung transplantation model.

Successful pulmonary artery stenting for occlusion at a constructed pericardial conduit after right upper double sleeve lobectomy.

The patient was a 53-year-old man. His chief complaint was a cough and dyspnea on exertion. Computed tomography (CT) showed a 3-cm-diameter tumor in the right upper lobe with invasion from hilar lymph nodes to the superior vena cava, right main bronchus, and pulmonary artery.

Anticancer agent α-sulfoquinovosyl-acylpropanediol enhances the radiosensitivity of human malignant mesothelioma in nude mouse models.

Malignant pleural mesothelioma (MPM) is a highly malignant disease that develops after asbestos exposure. Although the number of MPM cases is predicted to increase, no effective standard therapies have been established. The novel radiosensitizer α-sulfoquinovosyl-acylpropanediol (SQAP) enhances the effects of γ-radiation in human lung and prostate cancer cell lines and in animal models.

Increased In Vitro Intercellular Barrier Function of Lung Epithelial Cells Using Adipose-Derived Mesenchymal Stem/Stromal Cells.

With the emergence of coronavirus disease-2019, researchers have gained interest in the therapeutic efficacy of mesenchymal stem/stromal cells (MSCs) in acute respiratory distress syndrome; however, the mechanisms of the therapeutic effects of MSCs are unclear. We have previously reported that adipose-derived MSCs (AD-MSCs) strengthen the barrier function of the pulmonary vessels in scaffold-based bioengineered rat lungs. In this study, we evaluated whether AD-MSCs could enhance the intercellular barrier function of lung epithelial cells in vitro using a transwell coculture system.

Expression of human CD47 in pig glomeruli prevents proteinuria and prolongs graft survival following pig-to-baboon xenotransplantation.

Background: Nephrotic syndrome is a common complication of pig-to-baboon kidney xenotransplantation (KXTx) that adversely affects outcomes. We have reported that upregulation of CD80 and down-regulation of SMPDL-3b in glomeruli have an important role in the development of proteinuria following pig-to-baboon KXTx. Recently we found induced expression of human CD47 (hCD47) on endothelial cells and podocytes isolated from hCD47 transgenic (Tg) swine markedly reduced phagocytosis by baboon and human macrophages.

Safety, efficacy, and analysis of key parameters after prophylactic administration of a sustained-release formulation of azithromycin in lung cancer surgery.

Background: The current use of prophylactic antibiotics for lung cancer surgery requires modification in aging individuals with impaired lung function. A sustained-release formulation of azithromycin (AZM-SR) could help resolve some of these challenges with its sustained antibacterial and anti-inflammatory effects. The aim of this study was to examine the safety and efficacy of AZM-SR in lung cancer surgery as well as its anti-inflammatory effect.

A randomized phase II study of S-1 monotherapy versus cisplatin with vinorelbine for completely resected stage II/IIIA non-small cell lung cancer: rationale and study protocol design for the LOGIK1702 study.

Background: The current standard postoperative treatment for stage II-IIIA non-small cell lung cancer (NSCLC) is a regimen of platinum doublet adjuvant chemotherapy. These regimens, which are the same as for solid NSCLC tumors, often cause severe adverse reactions in the treated patients. Therefore, an effective treatment regimen with fewer side effects is needed.

Preoperative tracheal resection and reconstruction simulations with patient-specific three-dimensional models.

Three-dimensional (3D) printers are increasingly being used for a variety of applications. In the surgical field, patient-specific organ models are increasingly being used as preoperative simulators for complicated surgeries. In this study, we describe the use of patient-specific 3D models for tracheal resection.

Protection of Pancreatic Islets Using Theranostic Silencing Nanoparticles in a Baboon Model of Islet Transplantation.

The long-term success of pancreatic islet transplantation (Tx) as a cure for type 1 diabetes remains limited. Islet loss after Tx related to apoptosis, inflammation, and other factors continues to limit Tx efficacy. In this project, we demonstrate a novel approach aimed at protecting islets before Tx in nonhuman primates (NHPs) (baboons) by silencing a gene (caspase-3) responsible for induction of apoptosis.

Enhanced airway stenting using a preoperative, three-dimensionally printed airway model simulation.

Three-dimensionally printed organ models that facilitate preoperative simulations have the potential to improve outcomes of surgical procedures. Here, we report a case involving a 54-year-old man diagnosed with lung cancer of the right upper bronchus that was invading the right main bronchus. A right upper lobectomy with carinoplasty was performed.

Surgery or stereotactic body radiotherapy for metachronous primary lung cancer? A propensity score matching analysis.

Objective: We compared outcomes after surgery or stereotactic body radiotherapy (SBRT) among patients with metachronous primary lung cancer (MPLC).

Methods: Patients with MPLC were treated with either surgery (2008-2018) or SBRT (2010-2018). We used propensity score matching (PSM) to reduce bias from various clinicopathological factors.

A case of emergent operation for a life-threatening infectious mediastinal cyst.

Purpose: Congenital mediastinal cysts are an uncommon but important diagnostic group. Most of these cysts are benign and asymptomatic in adults. However, some of them are clinically problematic due to the compression of neighboring organs, infection, or perforation.

Intra-bone bone marrow transplantation from hCD47 transgenic pigs to baboons prolongs chimerism to >60 days and promotes increased porcine lung transplant survival.

Background: We have recently demonstrated that human-CD47 (hCD47) expressed on endothelial cells of porcine lung xenografts extended median graft survival from 3.5 days to 8.7 days in baboons.

Transgenic expression of human CD47 reduces phagocytosis of porcine endothelial cells and podocytes by baboon and human macrophages.

Background: Our initial studies utilizing a galactosyl-α1-3-galactosyltransferase gene knockout (GalTKO) pig-to-baboon renal transplant model demonstrated that the early development of nephrotic syndrome has been a significant obstacle to the long-term survival of baboon recipients. We have recently documented that sphingomyelin phosphodiesterase-3 (SMPDL3b) and CD80 expressed on podocytes in porcine kidney grafts contribute to this complication. We have hypothesized that one regulator of immune function is CD47 and that incompatibilities in CD47 between pig and baboon could potentially affect macrophage function, increasing the susceptibility of the kidney grafts to immunologically induced injury.

Successful treatment based on molecular biological assessment of invasive anaplastic lymphoma kinase-positive inflammatory myofibroblastic tumor of the lung.

Background: Inflammatory myofibroblastic tumor (IMT) of the lung is rare. This disease often shows neoplastic features with anaplastic lymphoma kinase positiveness as well as inflammatory features, such as steroid-responsive immunoglobulin G4 (IgG4)-related sclerosing disease. Since many cases have been reported as advanced, various treatment strategies should be considered based on clinical and biological features of each case.

Adipose-derived mesenchymal stem cells attenuate rejection in a rat lung transplantation model.

Background: Immunosuppression following lung transplantation is a key aspect to the graft's survival. However, the well-known complications that are caused by immunosuppressive regimens present an opportunity to study ways to minimize the usage of these drugs. Recently, a promising discovery has been made pertaining to the immunomodulatory effects of adipose tissue-derived mesenchymal stem cells (ADMSCs) through their secretion of hepatocyte growth factor.

Upregulation of CD80 on glomerular podocytes plays an important role in development of proteinuria following pig-to-baboon xeno-renal transplantation - an experimental study.

We have previously reported that co-transplantation of the kidney with vascularized donor thymus from α-1,3-galactosyltransferase gene knockout pigs with an anti-CD154 with rituximab-based regimen led to improved xenograft survival in baboons with donor-specific unresponsiveness. However, nephrotic syndrome emerged as a complication in which the glomeruli showed mild mesangial expansion with similarities to minimal change disease (MCD) in humans. Since MCD is associated with CD80 expression in glomeruli and elevated urinary excretion, we evaluated a potential role for CD80 in xenograft nephropathy.

Remaining Physiological Barriers in Porcine Kidney Xenotransplantation: Potential Pathways behind Proteinuria as well as Factors Related to Growth Discrepancies following Pig-to-Kidney Xenotransplantation.

Considerable shortages in the supply of available organs continue to plague the field of solid organ transplantation. Despite changes in allocation, as well as the utilization of extended criteria and living donors, the number of patients waiting for organs continues to grow at an alarming pace. Xenotransplantation, cross-species solid organ transplantation, offers one potential solution to this dilemma.

GalT-KO pig lungs are highly susceptible to acute vascular rejection in baboons, which may be mitigated by transgenic expression of hCD47 on porcine blood vessels.

Background: Despite recent progress in survival times of xenografts in non-human primates, there are no reports of survival beyond 5 days of histologically well-aerated porcine lung grafts in baboons. Here, we report our initial results of pig-to-baboon xeno-lung transplantation (XLTx).

Methods: Eleven baboons received genetically modified porcine left lungs from either GalT-KO alone (n = 3), GalT-KO/humanCD47(hCD47)/hCD55 (n = 3), GalT-KO/hD47/hCD46 (n = 4), or GalT-KO/hCD39/hCD46/hCD55/TBM/EPCR (n = 1) swine.

Lung xenotransplantation.

Purpose Of Review: This review describes the most recent progress in xeno lung transplantation (XLTx) to date. It describes the potential mechanisms of early xeno lung graft loss, as well as the latest therapeutic strategies to overcome them.

Recent Findings: Using ex-vivo perfusion models of porcine lungs with human blood, the use of genetically modified pig lungs along with novel pharmaceutical approaches has recently been studied.

Transplantation of bioengineered rat lungs recellularized with endothelial and adipose-derived stromal cells.

Bioengineered lungs consisting of a decellularized lung scaffold that is repopulated with a patient's own cells could provide desperately needed donor organs in the future. This approach has been tested in rats, and has been partially explored in porcine and human lungs. However, existing bioengineered lungs are fragile, in part because of their immature vascular structure.

Evaluation of totally implantable central venous access devices with the cephalic vein cut-down approach: Usefulness of preoperative ultrasonography.

Background: The aims of this retrospective study, were to evaluate totally implantable central venous access device (TICVAD) implantation and to validate the efficacy of preoperative ultrasonography.

Methods: A total of 380 cases implanted with TICVADs were divided into four groups: cut-downs with ultrasonography (group A, n = 112); cut-downs without ultrasonography (group B, n = 37); venous puncture (group C, n = 122); and replacements using the existing catheter (group D, n = 109). Operation time, completion rate, and complications were compared.

The evolution of bronchoplasty and broncho-angioplasty as treatments for lung cancer: evaluation of 30 years of data from a single institution.

Objectives: The purpose of this study was to evaluate the factors contributing to the outcomes of bronchoplasty for lung cancer by analysing a single institution's data for a 30-year period.

Methods: A retrospective review of 213 patients who underwent bronchoplasty for lung cancer between 1980 and 2010 was undertaken. The patients were divided into two groups by the date of surgery: the first period was 1980-95, and the second period was 1996-2010.