[Jul. 10] 114th IRCMS Seminar

June 26 2024

We would like to inform you that the 114th IRCMS seminar has been scheduled as below.
* This IRCMS seminar is open to everyone.

Date      : July 10, 2024 (Wednesday)

Time      : 16:00-17:00

ZOOM　: Meeting ID: 923 1780 1780
            　 Passcode: IRCMSJul10

Speaker : Dr. Eiji Yoshihara (Lundquist Institute /UCLA)

Title        : Overcoming Barriers in Diabetes Therapy: Functional Selection, Mass Production, and Immune-Evasion of Stem Cell-Derived Islets

Abstract 

Human pancreatic islets are essential regulators of systemic lipid and glucose homeostasis. The dysfunction of islet hormone secretion or the loss of β cell mass plays a significant role in the pathogenesis of diabetes, often necessitating insulin therapy or islet replacement. Human induced pluripotent stem cells (hiPSCs) offer a promising alternative to cadaveric human pancreatic islets to cure diabetes. However, hiPSC-derived islets (hiPSC-islets) typically display functional immaturity and heterogeneity when generated in vitro. Moreover, even with autologous delivery, hiPSC-islets require lifelong immunosuppression due to heightened immune responses, particularly in type 1 diabetes (T1D) patients. Consequently, the functional selection, mass production, and immune protection of hiPSC-islets are critical challenges in stem cell-based therapies for diabetes. We found a novel functional maturation and heterogeneity marker, along with regulator gene functions, which can be used to select functional clusters of hiPSC-islets. Additionally, we developed technology, designed to address the current challenges of generating functional insulin-producing cells in a practical, scalable, and cost-effective manner. Finally, I will share the current progress of immune-protection of hiPSC-islets for transplantation therapy. These studies will outline a three-step approach involving functional selection, mass production, and immune protection for cell therapy in diabetes.

2-3 major papers:

1. Yoshihara, et al. Immune-evasive human islet-like organoids ameliorate diabetes. Nature. 2020 Oct;586(7830):606-611.
2. Yoshihara, et al. ERRγ Is Required for the Metabolic Maturation of Therapeutically Functional Glucose-Responsive β Cells. Cell Metab. 2016 Apr 12;23(4):622-34.