Organ (biology) | EPFL Graph Search

In a multicellular organism, an organ is a collection of tissues joined in a structural unit to serve a common function. In the hierarchy of life, an organ lies between tissue and an organ system. Tissues are formed from same type cells to act together in a function. Tissues of different types combine to form an organ which has a specific function. The intestinal wall for example is formed by epithelial tissue and smooth muscle tissue. Two or more organs working together in the execution of a specific body function form an organ system, also called a biological system or body system. An organ's tissues can be broadly categorized as parenchyma, the functional tissue, and stroma, the structural tissue with supportive, connective, or ancillary functions. For example, the gland's tissue that makes the hormones is the parenchyma, whereas the stroma includes the nerves that innervate the parenchyma, the blood vessels that oxygenate and nourish it and carry away its metabolic wastes, and t

Engineering Dynamic Hydrogels For In Vitro Organoid Culture

Delphine Lorraine Perle Blondel

Over the past decade, methods to culture stem cells in three dimensions have opened up a plethora of new opportunities for basic and translational research in the life sciences. In particular, the use of natural extracellular matrix (ECM) surrogates, such as mouse tumour-derived Matrigel, unleashed the possibility to recapitulate complex multicellular behaviours in vitro, culminating in the successful derivation of miniaturized organs, termed organoids. While organoids hold tremendous potential as model systems in basic biology, the translational potential of these systems is hampered by their strict dependency on animal-derived matrices that suffer from batch-to-batch variability, potential immunogenicity, and ethical concerns. Recent efforts in engineering covalently crosslinked synthetic hydrogels have attempted to substitute these ill-defined organoid culture systems. However, although these bio-artificial matrices have shown significant potential for 3D organoid culture, their stability and their inherent elastic nature hamper organoid development. Indeed, the native ECM, just like Matrigel, is a highly viscoelastic and dynamic 3D milieu that can relax in response to tissue-induced stress by breaking and subsequently rearranging its network, thus permitting cellular remodelling without compromising the macroscopic stability of the material over time. Therefore, there is a need to develop the next generation of synthetic organoid culture matrices, exhibiting in vivo-like stress-relaxation properties. This thesis provides a perspective on how chemically defined, bio-inspired hydrogels can be designed as potential replacements for native ECM-based matrices for 3D organoid culture. In contrast to traditional synthetic hydrogels that cannot accommodate the dynamic mechanical changes occurring during organoid development, four types of synthetic matrices were developed that are crosslinked, either fully or partially, through dynamic physical bonds. The introduction of such network dynamics is shown to facilitate key morphogenetic processes, such as tissue budding, that are normally absent in purely elastic networks. A unifying hypothesis emerging from these results is that stress relaxation is a crucial requirement for 3D organoid culture. The mechanisms by which stress relaxation influence ISC fate and organoid development remain to be further studied. Preliminary experiments indicated that the stem cells may sense and respond to these characteristics through differential activation of mechanosensing pathways including the transcriptional co-activator YAP. The dynamic hydrogels developed in this thesis hold great promise as tunable environments for stem cell-based self-organization, enabling morphogenetic processes that may be suppressed in conventional synthetic hydrogels systems predominantly used in 3D cell culture applications.

EPFL2019

Progress and potential in organoid research

Matthias Lütolf, Andrea Manfrin, Giuliana Rossi

Tissue and organ biology are very challenging to study in mammals, and progress can be hindered, particularly in humans, by sample accessibility and ethical concerns. However, advances in stem cell culture have made it possible to derive in vitro 3D tissues called organoids, which capture some of the key multicellular, anatomical and even functional hallmarks of real organs at the micrometre to millimetre scale. Recent studies have demonstrated that organoids can be used to model organ development and disease and have a wide range of applications in basic research, drug discovery and regenerative medicine. Researchers are now beginning to take inspiration from other fields, such as bioengineering, to generate organoids that are more physiologically relevant and more amenable to real-life applications.

2018

Engineering next generation organoids through guided stem cell self-organisation

Mikhail Nikolaev

One of the long-standing goals in the field of tissue engineering is the fabrication of de novo tissues or even organs to provide better tissue models for basic research and drug discovery, and to alleviate a shortage of donor organs in the future. Research in recent decades to understand tissue biology has led to the discovery of stem cell niches and the development of innovative protocols for the generation of three-dimensional in vivo-like tissues called organoids. Organoids represent multiple histological and functional aspects of real organs and offer unprecedented perspectives for modelling tissue development, regeneration, and disease in vitro. However, relying so far almost exclusively on spontaneous self-organisation of stem cells, organoids develop uncontrollably into small structures of highly variable size and architecture. Moreover, the closed, cystic architecture of most epithelial organoids limits their lifespan and makes experimental manipulation difficult. In this thesis, three innovative engineering technologies were developed that offer the possibility of steering in vitro stem cell patterning and organoid formation into more controllable and physiologically relevant miniature tissues.	The aim of the first project was to study how predefined geometric constraints, as they exist in vivo, affect organoid development. This required the development of a novel fabrication process of the topographically micro-patterned hydrogel surfaces. This approach allowed the generation of large arrays of the identical organoids, having pre-defined shape and size to study cellular mechanisms involved in the proper, stereotypical cell type pattering of intestinal organoids.		The second project focused on replicating tissue dynamics and aspects of organ physiology by developing a novel three-dimensional organ-on-chip approach. Using stem cells derived from patient biopsies, this technology enables to production of miniature versions of patientâs organs that can be used in personalized diagnostics and medical treatment assays.	Bioprinting has long been considered as one of the most promising technologies for fabricating organs in vitro. However, despite encouraging advances made in recent years, the degree of multicellular spatial complexity and function of organoids remains unmatched by any existing bioprinting technology. Therefore, the third project was aimed to develop a new bioprinting strategy that preserves local stem cell self-organization potential and extends organoids growth to the macroscopic scale.	Overall, this thesis introduces several cutting-edge technologies that offer the possibility to control in vitro organoid development and should therefore become efficient research tools to facilitate the translation of organoid technology towards pharmaceutical and clinical applications. Hydrogel micro-pattering is an efficient technology that can be widely used to explore the mechanisms by which tissue geometry can regulate morphogenesis of different organs and can be readily applied for high-throughput screening in pharmacological assays. The microscope-based bioprinter can be set-up in any laboratory to guide stem cell self-organization and tissue morphogenesis from millimetre to centimetre scales. The microfluidic organoid-on-chip concept should enable the creation of various miniature organs with complex three-dimensional spatial organisation and multicellular complexity for basic research and drug discovery.

EPFL2021