Organoid technology provides a revolutionary paradigm toward therapy but has yet to be applied in humans, mainly because of reproducibility and scalability challenges. Here, we overcome these limitations by evolving a scalable organ bud production platform entirely from human induced pluripotent stem cells (iPSC). By conducting massive "reverse" screen experiments, we identified three progenitor populations that can effectively generate liver buds in a highly reproducible manner: hepatic endoderm, endothelium, and septum mesenchyme. Furthermore, we achieved human scalability by developing an omni-well-array culture platform for mass producing homogeneous and miniaturized liver buds on a clinically relevant large scale (>10). Vascularized and functional liver tissues generated entirely from iPSCs significantly improved subsequent hepatic functionalization potentiated by stage-matched developmental progenitor interactions, enabling functional rescue against acute liver failure via transplantation. Overall, our study provides a stringent manufacturing platform for multicellular organoid supply, thus facilitating clinical and pharmaceutical applications especially for the treatment of liver diseases through multi-industrial collaborations.

Object. Gamma knife surgery (GKS) has been a safe and effective treatment for vestibular schwannomas in both the short and long term, although less is known about long-term outcomes in the past 10 years. The aim of this study was to clarify long-term outcomes in patients with vestibular schwannomas treated using GKS based on techniques in place in the early 1990s. Methods. Eighty patients harboring a vestibular schwannoma (excluding neurofibromatosis Type 2) were treated using GKS between May 1991 and December 1993. Among these, 73 patients were assessed; seven were lost to follow up. The median duration of follow up was 135 months. The mean patient age at the time of GKS was 56 years old. The mean tumor volume was 6.3 cm3, and the mean maximal and marginal radiation doses applied to the tumor were 28.4 and 14.6 Gy, respectively. Follow-up magnetic resonance images were obtained in 71 patients. Forty-eight patients demonstrated partial tumor remission, 14 had tumors that remained stable, and nine demonstrated tumor enlargement or radiation-induced edema requiring resection. Patients with larger tumors did not fare as well as those with smaller lesions. The actuarial 10-year progression-free survival rate was 87% overall, and 93% in patients with tumor volumes less than 10 cm3. No patient experienced malignant transformation. Conclusions. Gamma knife surgery remained an effective treatment for vestibular schwannomas for longer than 10 years. Although treatment failures usually occurred within 3 years after GKS, it is necessary to continue follow up in patients to reveal delayed tumor recurrence.

Stereotactic GKS is safe and effective, in the long term, as an adjuvant or boost therapy for residual or recurrent craniopharyngiomas after surgical removal and has minimal side effects. New treatment strategies must be devised to manage these tumors.

We report the first series demonstrating that GKS can be a safe and effective treatment for epilepsy related to HHs. We advocate marginal doses greater than or equal to 17 Gy and partial dose-planning when necessary, for avoidance of critical surrounding structures.

Chordoid glioma of the third ventricle is considered to be a benign glial tumor located exclusively in the mid-anterior portion of the third ventricle near the hypothalamus and optic nerves, with the histological features of a chordoma and immuno-labeling for glial fibrillary acidic protein. Unfortunately, the clinical outcome of chordoid glioma has been poor, even in patients receiving gross total or partial removal with or without radiotherapy. Three cases of chordoid glioma of the third ventricle were treated with less invasive microsurgery for pathological diagnosis or partial removal without neuro-endocrinological complication, followed by gamma knife radiosurgery using a lower marginal dose for the optic nerves and hypothalamus. Gamma knife radiosurgery was performed after open biopsy in two patients, and after partial removal in the third patient using a lower marginal dose of 10.5 to 12 Gy. Serial magnetic resonance imaging revealed gradual decrease or at least no change in the tumor size, without significant complication at follow up 70 and 66 months later in two cases. The third patient accidentally died 13 months after gamma knife treatment. We conclude that low dose gamma knife radiosurgery after less invasive microsurgery is both safe and effective for the control of chordoid glioma of the third ventricle over a very long follow-up period.