Organoids lie in the middle ground between the full complexity of in vivo organs and traditional two-dimensional (2D) cell cultures. Due to this, organoid models allow researchers to alter the genetic backgrounds of cells more easily, less expensively, and more quickly than generating new mouse models. The advantages of an organoid model vs. an in vivo model may be more obvious than that of a competing in vitro system, e.g., 2D cell lines, but that belies the crucial differences between the two. For instance, because organoids exist in three-dimensional (3D) hydrogels, mechanosensitive signaling pathways are prevented from being activated (as what occurs when cells are in direct contact with plastic or glass well bottoms) and causing differentiation away from pluripotent progenitors. As a result, organoids preserve more cellular diversity and original tissue function than two-dimensional cell cultures do. Furthermore, transplantation of organoids into in vivo systems yields tumors that develop more stroma and stromal components when compared to transplanted tumors from 2D cell lines. Such tumors, by contrast, tend to grow as dense collections of tumor cells: a growth pattern that is histologically less similar to tumors that originated de novo. While deep exploration of these subjects is outside the scope of this chapter, which is dedicated to the advantages of applying organoid models to immunological contexts, the results of these properties of organoids hold meaningful implications for the applications of organoids in immunological study and clinical practice. The combined ability of organoids to be easily manipulated, to recapitulate tissue dynamics, and to generate tumors more faithfully to real disease has made organoids a crucial tool for investigating the immune system’s function, role in disease, and therapeutics. This chapter will elucidate research contexts in the aforementioned areas into which organoids have carved out an irreplaceable niche with evidence from recent studies that demonstrate their advantages.

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The Role of Organoids for Investigating Immunological Function, Disease, and Therapy

  • Alexander Cicala

摘要

Organoids lie in the middle ground between the full complexity of in vivo organs and traditional two-dimensional (2D) cell cultures. Due to this, organoid models allow researchers to alter the genetic backgrounds of cells more easily, less expensively, and more quickly than generating new mouse models. The advantages of an organoid model vs. an in vivo model may be more obvious than that of a competing in vitro system, e.g., 2D cell lines, but that belies the crucial differences between the two. For instance, because organoids exist in three-dimensional (3D) hydrogels, mechanosensitive signaling pathways are prevented from being activated (as what occurs when cells are in direct contact with plastic or glass well bottoms) and causing differentiation away from pluripotent progenitors. As a result, organoids preserve more cellular diversity and original tissue function than two-dimensional cell cultures do. Furthermore, transplantation of organoids into in vivo systems yields tumors that develop more stroma and stromal components when compared to transplanted tumors from 2D cell lines. Such tumors, by contrast, tend to grow as dense collections of tumor cells: a growth pattern that is histologically less similar to tumors that originated de novo. While deep exploration of these subjects is outside the scope of this chapter, which is dedicated to the advantages of applying organoid models to immunological contexts, the results of these properties of organoids hold meaningful implications for the applications of organoids in immunological study and clinical practice. The combined ability of organoids to be easily manipulated, to recapitulate tissue dynamics, and to generate tumors more faithfully to real disease has made organoids a crucial tool for investigating the immune system’s function, role in disease, and therapeutics. This chapter will elucidate research contexts in the aforementioned areas into which organoids have carved out an irreplaceable niche with evidence from recent studies that demonstrate their advantages.