Highlights d IRE1a deletion in NOD b cells before insulitis causes their transient dedifferentiation d Dedifferentiated b cells show diminished expression of b cell autoantigens d Knockout mice exhibit impaired T cell diabetogenic activity d IRE1a-deficient NOD mice are protected from autoimmune destruction and diabetes

Patient-derived model systems are important tools for studying novel anti-cancer therapies. Patient-derived xenografts (PDXs) have gained favor over the last 10 years as newer mouse strains have improved the success rate of establishing PDXs from patient biopsies. PDXs can be engrafted from head and neck cancer (HNC) samples across a wide range of cancer stages, retain the genetic features of their human source, and can be treated with both chemotherapy and radiation, allowing for clinically relevant studies. Not only do PDXs allow for the study of patient tissues in an in vivo model, they can also provide a renewable source of cancer cells for organoid cultures. Herein, we review the uses of HNC patient-derived models for radiation research, including approaches to establishing both orthotopic and heterotopic PDXs, approaches and potential pitfalls to delivering chemotherapy and radiation to these animal models, biological advantages and limitations, and alternatives to animal studies that still use patient-derived tissues.

Thorough research on the capacity of human islet transplantation to cure type 1 diabetes led to the achievement of 3-to 5-year-long insulin independence in nearly half of transplanted patients. Yet, translation of this technique to clinical routine is limited by organ shortage and the need for long-term immunosuppression, restricting its use to adults with unstable disease. The production of new bona fide β cells in vitro was thus investigated and finally achieved with human pluripotent stem cells (PSCs). Besides ethical concerns about the use of human embryos, studies are now evaluating the possibility of circumventing the spontaneous tumor formation associated with transplantation of PSCs. These issues fueled the search for cell candidates for β-cell engineering with safe profiles for clinical translation. In vivo studies revealed the regeneration capacity of the exocrine pancreas after injury that depends at least partially on facultative progenitors in the ductal compartment. These stimulated subpopulations of pancreatic ductal cells (PDCs) underwent β-cell transdifferentiation through reactivation of embryonic signaling pathways. In vitro models for expansion and differentiation of purified PDCs toward insulin-producing cells were described using cocktails of growth factors, extracellular-matrix proteins and transcription factor overexpression. In this review, we will describe the latest findings in pancreatic β-cell mass regeneration due to adult ductal progenitor cells. We will further describe recent advances in human PDC transdifferentiation to insulin-producing cells with potential for clinical translational studies.

Patient derived model systems are important tools for studying novel anti-cancer therapies. Patient derived xenografts (PDXs) have gained favor over the last 10 years as newer mouse strains have improved the success rate of establishing PDXs from patient biopsies. PDXs can be engrafted from head and neck cancer (HNC) samples across a wide range of cancer stages, retain the genetic features of their human source, and can be treated with both chemotherapy and radiation, allowing for clinically relevant studies. Not only do PDXs allow for study of patient tissues in an in vivo model, they can also provide a renewable source of cancer cells for organoid cultures. Herein, we review the uses of HNC patient derived models for radiation research including approaches to establishing both orthotopic and heterotopic PDXs, approaches and potential pitfalls to delivering chemotherapy and radiation to these animal models, biological advantages and limitations, and alternatives to animal studies that still use patient-derived tissues.

Autophagy is an evolutionarily conserved cell survival mechanism that degrades damaged proteins and organelles to generate cellular energy during times of stress.Recycling of these cellular components occurs in a series of sequential steps with multiple regulatory points. Mechanistic dysfunction can lead to a variety of human diseases and cancers due to the complexity of autophagy and its ability to regulate vital cellular functions. The role that autophagy plays in both the development and treatment of cancer is highly complex, especially given the fact that most cancer therapies modulate autophagy. This review aims to discuss the balance of autophagy in the development, progression, and treatment of head and neck cancer, as well as highlighting the need for a deeper understanding of what is still unknown about autophagy.