The resectable liver volume is strictly limited and this reduces the number of patients who may be treated. Recently, “tissue/organ decellularization”, a new approach in bioengineering, has been investigated for its ability to produce a native organ scaffold by removing all the viable cells. Such a scaffold may support the repair of damaged or injured tissue. The purpose of this study was to evaluate the potential contribution of liver scaffolds to hepatic regeneration after hepatectomy. We sutured the partial liver scaffolds onto the surfaces of partially hepatectomized porcine livers and assessed their therapeutic potential by immune histological analysis at various time points. Animals were sacrificed after surgery and the implanted scaffolds were evaluated for the infiltration of various types of cells. Immune histochemical study showed that blood vessel-like structures, covered with CD31 positive endothelial cells and ALB positive cells, were present in all parts of the scaffolds at days 10 and 28. Blood inflow was observed in some of these ductal structures. More interestingly, CK19 and EpCAM positive cells appeared at day 10. These results suggest that the implantation of a decellularized organ scaffold could promote structural reorganization after liver resection.

Unlimited organ availability would represent a paradigm shift in transplantation. Long-term in vivo engraftment and function of scaled-up bioengineered liver grafts have not been previously reported. In this study, we describe a human-scale transplantable liver graft engineered on a porcine liver-derived scaffold. We repopulated the scaffold parenchyma with primary hepatocytes and the vascular system with endothelial cells. For in vivo functional testing, we performed auxiliary transplantation of the repopulated scaffold in pigs with induced liver failure. It was observed that the auxiliary bioengineered liver graft improved liver function for 28 days and exhibited upregulation of liver-specific genes. This study is the first of its kind to present 28 days of posttransplant evaluation of a bioengineered liver graft using a preclinical large animal model. Furthermore, it provides definitive evidence for the feasibility of engineering human-scale transplantable liver grafts for clinical applications.

This study aimed to examine the effect of mesalazine on fertility. In this retrospective analysis of 1,225 male subfertile patients, we reviewed the cases of inflammatory bowel disease (IBD) in the medical records and evaluated the prevalence of the disease in our reproduction center. Specifically, we examined IBD patients who ceased mesalazine during male infertility treatment, and compared the seminogram of these patients before and after discontinuation of mesalazine. We also analyzed pregnancy outcome after discontinuation. The prevalence rate of Crohn's disease and ulcerative colitis in our male infertile patients was 163 per 100,000 men and 490 per 100,000 men, respectively. Seven patients had taken mesalazine and six of them subsequently stopped the medication. The mean values of sperm concentration, sperm motility, percentage of normal formed sperm, semen volume, and total motile sperm count taken before discontinuation increased after discontinuation of mesalazine. Among these parameters, the sperm motility and total motile sperm count were significantly improved (p < 0.05) after discontinuation. Of the six patients who stopped the drug, four achieved pregnancy with their partners, with two of the four men showing significant improvement not only in the percentage of normal shaped sperm but also sperm motility and total motile sperm count. This study provides further insight into the rarely investigated relationship between male fertility and mesalazine.

It has not been considered that nephrons regenerate in adult mammals. We present that an organ-derived extracellular matrix in situ induces nephron regeneration in a preclinical model. A porcine kidney-derived extracellular matrix was sutured onto the surface of partial nephrectomy (PN)-treated kidney. Twenty-eight days after implantation, glomeruli, vessels, and renal tubules, characteristic of nephrons, were histologically observed within the matrix. No fibrillogenesis was observed in the matrix nor the matrix-sutured kidney, although this occurred in a PN kidney without the matrix, indicating the structures were newly induced by the matrix. The expression of renal progenitor markers, including Sall1, Six2, and WT-1, within the matrix supported the induction of nephron regeneration by the matrix. Furthermore, active blood flow was observed inside the matrix using computed tomography. The matrix provides structural and functional foundations for the development of cell-free scaffolds with a remarkably low risk of immune rejection and cancerization.