Human liver organoids generated with single donor-derived multiple cells rescue mice from acute liver failure

BackgroundAcute liver failure (ALF) is a life-threatening disease with a high mortality rate. However, there are limited treatments or devices available for ALF therapy. Here, we aimed to develop a new strategy for ALF treatment by transplanting functional liver organoids (LOs) generated from single donor-derived human induced pluripotent stem cell (hiPSC) endoderm, endothelial cells (ECs), and mesenchymal cells (MCs).MethodsFirst, we isolated ECs and MCs from a single donor umbilical cord (UC) through enzyme digestion and characterized the UC-ECs and UC-MCs by flow cytometry. Second, using a nonviral reprogramming method, we generated same donor-derived hiPSCs from the UC-ECs and investigated their hepatic differentiation abilities. Finally, we simultaneously plated EC-hiPSC endoderm, UC-ECs, and UC-MCs in a three-dimensional (3D) microwell culture system, and generated single donor cell-derived differentiated LOs for ALF mouse treatment.ResultsWe obtained ECs and MCs from a single donor UC with high purity, and these cells provided a multicellular microenvironment that promoted LO differentiation. hiPSCs from the same donor were generated from UC-ECs, and the resultant EC-hiPSCs could be differentiated efficiently into pure definitive endoderm and further into hepatic lineages. Simultaneous plating of EC-hiPSC endoderm, UC-ECs, and UC-MCs in the 3D microwell system generated single donor cell-derived LOs (SDC-LOs) that could be differentiated into functional LOs with enhanced hepatic capacity as compared to that of EC-hiPSC-derived hepatic-like cells. When these functional SDC-LOs were transplanted into the renal subcapsules of ALF mice, they rapidly assumed hepatic functions and improved the survival rate of ALF mice.ConclusionThese results demonstrate that functional LOs generated from single donor cells can improve the condition of ALF mice. Functional SDC-LO transplantation provides a promising novel approach for ALF therapy

A Second Look or, Not to Mention the Occasional Capsizing of a Windsurfer

Of all of the epithelial ovarian cancers (EOC), clear cell adenocarcinoma (CCA) has the worst clinical prognosis. Furthermore, the conventional EOC biomarker CA125 is more often negative in CCA than in other subtypes of EOC. This study sought to discover a new diagnostic biomarker that would allow more reliable detection of CCA. Using mass spectrometry, we compared proteins in conditioned media from cell lines derived from CCA and other types of EOC. We identified 30 extracellular or released proteins specifically present in CCA-derived cell lines. Bioinformatics analyses identified a serine protease inhibitor, tissue factor pathway inhibitor 2 (TFPI2), as a potential biomarker for CCA. Real time RT-PCR and Western blot analyses revealed that TFPI2 was exclusively expressed in CCA-derived cell lines and tissues. For clinical validation, we measured levels of TFPI2 and CA125 in a set of sera from 30 healthy women, 30 patients with endometriosis, and 50 patients with CCA, using an automated enzyme-linked immunosorbent assay systems. Serum levels of TFPI2 were significantly elevated in CCA patients, even those with normal CA125 levels. In terms of area under the receiver operating characteristic curve (AUC), TFPI2 was superior to CA125 in discriminating CCA patients from healthy women (AUC 0.97 for TFPI2 versus AUC 0.80 for CA125), or from patients with endometriosis (AUC 0.93 for TFPI2 versus 0.80 for CA125). This is the first evidence for TFPI2 as a serum biomarker of CCA. We propose that this biomarker may be useful for detection of CCA and for monitoring the transformation from endometriosis into CCA

Risk factors for HPV infection and high-grade cervical disease in sexually active Japanese women

Funding Information: This work was supported by the Health and Labor Sciences Research Grant [26272001] and the Japanese Agency for Medical Research and Development [JP15ck0106103].Peer reviewedPublisher PD

Bivalent Human Papillomavirus Vaccine Effectiveness in a Japanese Population : High Vaccine-Type-Specific Effectiveness and Evidence of Cross-Protection

Acknowledgments.  We thank Dr Tomomi Egawa-Takata, Dr Akiko Morimoto, Dr Yusuke Tanaka, Ms Asami Yagi, Ms Yuka Watanabe, Ms Sachiko Ono, Ms Anna Ishida, and the administrators of Niigata, Nagaoka, Shibata, Sanjo, Joetsu, and Mitsuke cities for their support in conducting the survey. Financial support. This work was supported by the Health and Labor Sciences Research Grant (26272001) and the Japanese Agency for Medical Research and Development (AMED) under grant number JP15ck0106103 and JP17ck0106369.Peer reviewedPublisher PD

Suspension of proactive recommendations for HPV vaccination has led to a significant increase in HPV infection rates in young Japanese women : real-world data

Funding Information: We would like to thank Ms. Yuka Watanabe, Ms. Sachiko Ono, Ms. Anna Ishida, and administrator of Niigata city for their support in conducting the survey. This work was supported by the Japanese Agency for Medical Research and Development (JP15ck0106103).Peer reviewedPublisher PD

Epidemiologic profile of type-specific human papillomavirus infection after initiation of HPV vaccination

Funding Information: This work was supported by the Health and Labor Sciences Research Grant [26272001] and the Japanese Agency for Medical Research and Development [JP15ck0106103]. Acknowledgments: We would like to thank Yuka Watanabe, Sachiko Ono, Anna Ishida, Yoko Motoki and the administrator of Niigata city for their support in conducting the surveyPeer reviewedPublisher PD

Japan's Ongoing Crisis on HPV Vaccination.

Funding: This work was supported by the Health and Labor Sciences Research Grant [26272001] and the Japanese Agency for Medical Research and Development [JP15ck0106103]. Acknowledgments: We would like to thank Yuka Watanabe, Sachiko Ono, Anna Ishida, Yoko Motoki, Tomomi Egawa-Takata, Akiko Morimoto, Yusuke Tanaka and the administrator of Niigata city for their support in conducting the surveyPeer reviewedPublisher PD

Internet Survey of Awareness and Behavior Related to HPV Vaccination in Japan

Funding Information: Funding: This work was supported by the Health and Labor Sciences Research Grant No. 26272001 and the Japanese Agency for Medical Research and Development (JP15ck0106103).Peer reviewedPublisher PD

Effectiveness of human papillomavirus vaccine against cervical precancer in Japan : Multivariate analyses adjusted for sexual activity.

ACKNOWLEDGMENTS We would like to thank Mr Kenshin Sekine and Mr Taishin Sekine for English editing, and Ms Yuka Watanabe, Ms Sachiko Ono, Ms Anna Ishida, and administrators of Niigata, Nagaoka, Joetsu, Shibata, Sanjo, Mitsuke city for their support in conducting the survey.Peer reviewedPublisher PD