Transplantation of human iPSC-derived muscle stem cells in the diaphragm of Duchenne muscular dystrophy model mice

マウスの横隔膜にヒトiPS細胞から作った骨格筋幹細胞を移植する --デュシェンヌ型筋ジストロフィーの呼吸筋治療に向けた横隔膜移植方法の確立--. 京都大学プレスリリース. 2022-04-13.Duchenne muscular dystrophy (DMD) is an intractable genetic muscular disorder characterized by the loss of DYSTROPHIN. The restoration of DYSTROPHIN is expected to be a curative therapy for DMD. Because muscle stem cells (MuSCs) can regenerate damaged myofibers with full-length DYSTROPHIN in vivo, their transplantation is being explored as such a therapy. As for the transplanted cells, primary satellite cells have been considered, but donor shortage limits their clinical application. We previously developed a protocol that differentiates induced pluripotent stem cells (iPSCs) to MuSCs (iMuSCs). To ameliorate the respiratory function of DMD patients, cell transplantation to the diaphragm is necessary but difficult, because the diaphragm is thin and rapidly moves. In the present study, we explored the transplantation of iMuSCs into the diaphragm. First, we show direct cell injection into the diaphragm of mouse was feasible. Then, to enhance the engraftment of the transplanted cells in a rapidly moving diaphragm, we mixed polymer solutions of hyaluronic acid, alginate and gelatin to the cell suspension, finding a solution of 20% dissolved hyaluronic acid and 80% dissolved gelatin improved the engraftment. Thus, we established a method for cell transplantation into mouse diaphragm and show that an injectable hyaluronic acid-gelatin solution enables the engraftment of iMuSCs in the diaphragm

Uneven acute non-alcoholic fatty change of the liver after percutaneous transhepatic portal vein embolization in a patient with hilar cholangiocarcinoma – a case report

Abstract Background Portal vein embolization is essential for patients with biliary cancer who undergo extended hepatectomy to induce hypertrophy of the future remnant liver. Over 830 patients have undergone the portal vein embolization at our institution since 1990. Non-alcoholic fatty liver disease is an entity of hepatic disease characterized by fat deposition in hepatocytes. It has a higher prevalence among persons with morbid obesity, type 2 diabetes, and hyperlipidemia. Neither the mechanism of hepatic hypertrophy after portal vein embolization nor the pathophysiology of non-alcoholic fatty liver disease has been fully elucidated. Some researchers integrated the evident insults leading to progression of fatty liver disease into the multiple-hit hypothesis. Among these recognized insults, the change of hemodynamic status of the liver was never mentioned. Case presentation We present the case of a woman with perihilar cholangiocarcinoma who received endoscopic biliary drainage and presented to our institute for surgical consultation. A left trisectionectomy with caudate lobectomy and extrahepatic bile duct resection was indicated for curative treatment. To safely undergo left trisectionectomy, she underwent selective portal vein embolization of the liver, in which uneven acute fatty change subsequently developed. The undrained left medial sector of the liver with dilated biliary tracts was spared the fatty change. The patient underwent planned surgery without any major complications 6 weeks after the event and has since resumed a normal life. The discrepancies in fatty deposition in the different sectors of the liver were confirmed by pathologic interpretations. Conclusion This is the first report of acute fatty change of the liver after portal vein embolization. The sparing of the undrained medial sector is unique and extraordinary. The images and pathologic interpretations presented in this report may inspire further research on how the change of hepatic total inflow after portal vein embolization can be one of the insults leading to non-alcoholic fatty liver disease/ change

Current Status on Cholangiocarcinoma and Gallbladder Cancer

Cholangiocarcinomas (CC) as well as gallbladder cancers are relatively rare and intractable diseases. Clinical, pathological, and epidemiological studies on these tumors have been under investigation. The current status and/or topics on biliary tract cancers have been reported in the East West Association of Liver Tumor (EWALT), held in Milano, Italy in 2015

Long-term survival after multidisciplinary therapy for residual gallbladder cancer with peritoneal dissemination: a case report

Abstract Background Although surgical resection is the only curative treatment for gallbladder cancer (GBC), concomitant peritoneal dissemination is considered far beyond the scope of resection. We report a long-term survivor with a residual GBC with multiple peritoneal disseminations who underwent an extended resection after effective chemotherapy. Case presentation A 59-year-old male underwent an open cholecystectomy for Mirizzi syndrome at a local hospital. Because of severe inflammation, the gallbladder was perforated during surgery, ending in a piecemeal resection. A pathological examination revealed GBC with positive margins, and the patient was referred to our hospital 1 month after surgery for further treatment. A multidetector-row computed tomography (MDCT) showed three hypoattenuated tumours: a tumour (3.9 cm) at the left medial segment corresponding to the gallbladder bed, a tumour (1.8 cm) around the hepatic flexure of the transverse colon, and a tumour (1.0 cm) at the stump of the cystic duct. Percutaneous needle biopsy was performed, which provided histologic evidence of adenocarcinoma. Thus, the patient had a rapidly progressive local relapse with limited peritoneal dissemination, labelled ycT3N0M1, stage IVB disease according to the UICC system. After the administration of 3 cycles of gemcitabine plus cisplatin combination chemotherapy, the size of all tumours and the CA19-9 level decreased significantly. Since the patient’s general condition and liver function reserve were satisfactory, we decided the initial unresectable scenario to perform surgical therapy. After portal vein embolization, right hepatectomy, resection of the extrahepatic bile duct, partial duodenectomy, and partial colectomy were performed. Operative time was 555 min, and intraoperative blood loss was 1654 mL. Pathologic diagnosis of residual gallbladder carcinoma with peritoneal dissemination was confirmed, and the surgical margins were tumour-free. The patient was discharged on postoperative day 29, with a Clavien-Dindo IIIa complication (abdominal wall abscess). Postoperative adjuvant chemotherapy with tegafur/gimeracil/oteracil was administered during 1 year after surgery. The patient is doing well 6 years after the second surgery without evidence of disease. Conclusions Although specific clinical factors were associated with a favourable outcome in this patient, the present report suggests that multidisciplinary therapy may be a promising option in selected patients with distant metastatic GBC

Application of fluorescent cholangiography during single-incision laparoscopic cholecystectomy for cholecystitis with a right-sided round ligament: Preliminary experience

An 82-year-old woman was diagnosed with cholecystitis with a right-sided round ligament. We planned a single-incision laparoscopic cholecystectomy. Based on the findings of fluorescent cholangiography, the running course of the common bile duct was confirmed before dissection of Calot's triangle, and the confluence between the cystic duct and the common bile duct was exposed after the dissection of Calot's triangle. The planned surgery was successful. The operative time and intraoperative blood loss were 157 min and 2 mL, respectively. The patient was discharged from our hospital 3 days after surgery. Application of fluorescent cholangiography during a laparoscopic cholecystectomy for the patients with a right-sided round ligament should be widely accepted