Three-dimensional organotypic culture: experimental models of mammalian biology and disease

Abstract

Mammalian organs are challenging to study as they are fairly inaccessible to experimental manipulation and optical observation. Recent advances in three-dimensional (3D) culture techniques, coupled with the ability to independently manipulate genetic and microenvironmental factors, have enabled the real-time study of mammalian tissues. These systems have been used to visualize the cellular basis of epithelial morphogenesis, to test the roles of specific genes in regulating cell behaviours within epithelial tissues and to elucidate the contribution of microenvironmental factors to normal and disease processes. Collectively, these novel models can be used to answer fundamental biological questions and generate replacement human tissues, and they enable testing of novel therapeutic approaches, often using patient-derived cells.

3D Miniaturization of Human Organs for Drug Discovery

“…[53] In these multicellular aggregates, the need for supporting gels or matrices is eliminated, the adverse effects 3D culture approach for generating a laminated cerebral cortex like structure from pluripotent stem cells. [57,58] Microfabrication Neuroprogenitor cells Microfluidic culture platform containing a relief pattern of soma and axonal compartments connected by microgrooves to direct, isolate, lesion, and biochemically analyze CNS axons [67,68] 3D bioprinting Primary human cortical neurons Discrete layers of primary neutrons in a RGD peptide-modified gellan gum [118][119][120] Intestine (Gut) Self-assembled Stem cells Identified intestinal stem cells and differentiated cells in vitro [59,60] Microfabrication Human epithelial cells Mimic contractility by using mechanochemical actuator [11,19,27,72] Liver Self-assembled Human stem cells 3D culture of self-renewing human liver tissue [61,62] Microfabrication Hepatocytes and fibroblasts Microengineered hepatic microtissues containing hepatocytes and fibroblasts [73][74][75][76][77] 3D bioprinting HepG2 and HUVEC Multilayered organ tissue model [96,[155][156][157] Vessel Microfabrication Rat brain endothelial cells 3D culture in microfluidic device [63][64][65][66] 3D bioprinting HUVECs and HUVSMCs Scaffold-less vessel formation using spheroid fusion [84][85][86][87][88][89][90][91]…”

“…High-throughput pharmacological study [36,78] 3D bioprinting Primary feline H1 cardiomyocytes First rhythmic beating of 3D printed structure [93][94][95] Lung Microfabrication Epithelial cells Use of porous membrane to mimic lung functions [31,37] 3D bioprinting A549 cells and EA hy926 cells World's first 3D bioprinted lung tissue [101] Bone 3D bioprinting BMSCs High viability in microextrusion-based bioprinting [108,109,158,159] Cancer Self-assembled Intestinal stem cells Discovery of LGR5+ intestinal stem cells [52,62] Microfabrication Breast cancer cells Perfusable human microvascularized bone-mimicking (BMi) microenvironment [81,168] 3D bioprinting OVCAR-5 and MRC-5 cells Insight into complex cell-cell communication in 3D [113][114][115][116][117] Multi Self-assembled Liver, gut, vessel cells High throughput hanging drop [30,[49][50][51][52] Microfabrication Liver, heart, and vessel cells Automated control of perfusion [11,19,27,32] 3D bioprinting NPC and HCT-116 cells Multiorgan bioprinted model [30,122] a)…”

“…[9][10][11] In 2D conditions, cells are grown on solid-phased substrates while other surface is exposed to synthetic liquidphased media. In contrast, a 3D extracellular matrix (ECM) provides mechanical and biochemical clues in vivo.…”

Perspectives on the Molecular and Biological Implications of Tropoelastin in Human Tissue Elasticity

“…[1] This interplay means that their biopolymer components need to not only deliver durable tensile and compression performance, they also need to participate in cross-talk with other resident molecules and with cells. [2,3] That harmony encompasses the flow of blood through the vasculature to exchange gases and nutrients, the nurtured functionality of resident and visiting cells, and local physical integrity. [4,5] De novo synthesis of tissue is often inadequate as evidenced by scars and the shut-down in elastin synthesis after childhood.…”

Research Update: Electrical monitoring of cysts using organic electrochemical transistors

“…2 Due to the fact that cysts and spheroids retain cell architecture, function, and cell-cell interactions as in vivo, models have been successfully used in this format for toxicological studies, showing greater predictive qualities than 2D counterparts. 1,3,4 In one example, prostate cancer cell microaggregates or spheroids were shown to be more resistance to Docetaxel, a representative cancer drug routinely used in prostate cancer treatment, than the same cells cultured in monolayers.…”