Bioengineered livers (BELs) are an attractive therapeutic alternative to address the donor organ shortage for liver transplantation. The goal of BELs technology aims at replacement or regeneration of the native human liver. A variety of approaches have been proposed for tissue engineering of transplantable livers; the current review will highlight the decellularization-recellularization approach to BELs. For example, vascular patency and appropriate cell distribution and expansion are critical components in the production of successful BELs. Proper solutions to these components of BELs have challenged its development. Several strategies, such as heparin immobilization, heparin-gelatin, REDV peptide, and anti-CD31 aptamer have been developed to extend the vascular patency of revascularized bioengineered livers (rBELs). Other novel methods have been developed to enhance cell seeding of parenchymal cells and to increase graft functionality during both bench and in vivo perfusion. These enhanced methods have been associated with up to 15 days of survival in large animal (porcine) models of heterotopic transplantation but have not yet permitted extended survival after implantation of BELs in the orthotopic position. This review will highlight both the remaining challenges and the potential for clinical application of functional bioengineered grafts.

Background: Biological organ engineering is a novel experimental approach to generate functional liver grafts by decellularization and repopulation. Currently, healthy organs of small or large animals and human organs with preexisting liver diseases are used to optimize decellularization and repopulation. However, the effects of morphological changes on allo-and xenogeneic cell-scaffold interactions during repopulation procedure, e.g., using scaffold-sections, are unknown. We present a sequential morphological workflow to identify murine liver scaffold-sections with well-preserved microarchitecture. Methods: Native livers (CONT, n ¼ 9) and livers with experimentally induced pathologies (hepatics steatosis: STEA, n ¼ 7; hepatic fibrosis induced by bile duct ligation: BDL, n ¼ 9; nodular regenerative hyperplasia induced by 90% partial hepatectomy: PH, n ¼ 8) were decellularized using SDS and Triton X-100 to generate cell-free scaffolds. Scaffold-sections were assessed using a sequential morphological workflow consisting of macroscopic, microscopic and morphological evaluation: (1) The scaffold was evaluated by a macroscopic decellularization score. (2) Regions without visible tissue remnants were localized for sampling and histological processing. Subsequent microscopical examination served to identify tissue samples without cell remnants. (3) Only cell-free tissue sections were subjected to detailed liver-specific morphological assessment using a histological and immunohistochemical decellularization score. Results: Decellularization was feasible in 33 livers, which were subjected to the sequential morphological workflow. In 11 of 33 scaffolds we achieved a good macroscopic decellularization result (CONT:

Background: The Milan criteria (MC) are widely used for the indication of liver transplantation (LTx) in hepatocellular carcinoma (HCC). Good long-term results have also been reported following LTx for patients exceeding the MC. In this article, we compare the overall and recurrence-free survival of our patients fulfilling and exceeding the MC according to the post-transplant histopathological results. Patients and methods: Data from 120 patients with HCC (22 females and 98 males) were analyzed. The median patient age was 61 years (Q1, Q3 54.7, 65.4), and the median MELD score was 11 (Q1, Q3 8, 15). The median follow-up period was 53 months (Q1, Q3 16.6, 78). Patients were categorized into established criteria (MC, up-to-seven (UTS), Asan criteria, AFP score), and the outcome of the individual groups was compared. Results: Seventy-four of 120 patients fulfilled the MC, 86 patients met the UTS criteria, 85 patients fulfilled the Asan criteria, and 79 patients had an AFP score less than or equal to 2. The 1-and 5-year survival rates of all patients were 76.7% and 55.6%, respectively. In total, 14.2% of all patients (5.4% of patients who met the MC, 7% of patients who met the UTS criteria, 5.9% of patients who met the Asan criteria, and 6.3% of patients who had an AFP score less than 2) experienced recurrence. Conclusions: The outcomes of the patients were comparable to those reported in the current literature. In our population, similar recurrence and survival rates of the patients were noted for patients fulfilling the UTS criteria irrespective of fulfilling or exceeding the MC. Consequently, we consider using UTS criteria as the extended criterion for LTx indication.

Liver transplant is a curative therapy for selected patients with irresectable Klatskin tumors, but further prospective studies are urgently needed.

Purpose In patients suffering from autosomal dominant polycystic liver and kidney disease (ADPLKD), combined organ transplantation often poses a technical challenge due to the large volume of both organs. To simplify the transplantation procedure by improving the exposure of anatomical structures, we introduce a novel surgical technique of orthotopic liver and kidney transplantation. Methods The modified simultaneous liver and kidney transplantation technique via a right-sided L-incision included three steps: (1) right-sided nephrectomy in the recipient followed by (2) orthotopic liver transplantation in cava replacement technique and (3) the orthotopic kidney transplantation with arterial reconstruction to the right common iliac artery. Results In total, seven patients with ADPLKD were transplanted by using the modified transplantation technique. The mean operation time was 342.43 min (±68.77). Postoperative patients were treated for 6.28 days (±2.50) in the intensive care unit and were discharged from the surgical ward approximately 28 days (±5.66) after the operation with normal graft function. Complications associated with the use of the modified technique, such as bleeding, anastomotic stenosis, biloma, or urinoma, did not occur. Conclusion Modified simultaneous liver and kidney transplantation is a safe alternative for patients with ADPLKD. By combining right-sided nephrectomy and orthotopic graft transplantation, the approach optimizes the exposure of anatomical structures and simplifies the transplantation procedure. Additionally, the modified transplantation technique does not require a particular organ explantation procedure and can be applied for all liver and kidney grafts.

Background Physicians are faced with a growing number of patients after renal transplantation undergoing graft-unrelated surgery. So far, little is known about the postoperative restitution of graft function and the risk factors for a poor outcome. Methods One hundred one kidney transplant recipients undergoing graft-unrelated surgery between 2005 and 2015 were reviewed retrospectively. A risk analysis was performed and differences in creatinine, GFR and immunosuppressive treatment were evaluated. Additional, a comparison with a case-matched non-transplanted control group were performed. Results Preoperative creatinine averaged 1.88 mg / dl [0.62–5.22 mg / dl] and increased to 2.49 mg / dl [0.69–8.30 mg / dl] postoperatively. Acute kidney failure occurred in 18 patients and 14 patients had a permanent renal failure. Significant risk factors for the development of postoperative renal dysfunction were female gender, a preoperative creatinine above 2.0 mg / dl as well as a GFR below 40 ml / min and emergency surgery. Patients with tacrolimus and mycophenolate mofetil treatment showed a significant lower risk of renal dysfunction than patients with other immunosuppressants postoperatively. Contrary to that, the risk of patients with cyclosporine treatment was significantly increased. Transplanted patients showed a significantly increased rate of postoperative renal dysfunction. Conclusions The choice of immunosuppressant might have an impact on graft function and survival of kidney transplant recipients after graft-unrelated surgery. Further investigations are needed. Electronic supplementary material The online version of this article (10.1186/s12882-019-1358-2) contains supplementary material, which is available to authorized users.

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MP dynamics within the first period of transplantation could help to clarify on-going mechanisms of immunomodulation.