Directed Differentiation of Human Induced Pluripotent Stem Cells into Fallopian Tube Epithelium

Yucer, Nur; Holzapfel, Marie; Vogel, Tilley Jenkins; Lenaeus, Lindsay; Ornelas, Loren; Laury, Anna; Sareen, Dhruv; Barrett, Robert J.; Karlan, Beth Y.

doi:10.1038/s41598-017-05519-2

Cited by 61 publications

(65 citation statements)

References 36 publications

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“…Fallopian tube organoid in vitro models have also been generated from induced pluripotent stem cells (iPSCs). Yucer et al guided differentiation of iPSC lines into fallopian tube epithelium precursor cells through exposure to BMP4 and WNT4 followed by follistatin, an activin-binding protein that bio-neutralizes members of the TGF-β superfamily [ 35 ]. When spheroids of these differentiated cells were grown on Matrigel and supplemented with estrogen, progesterone, and crucially, conditioned media from primary fallopian tube epithelial cells, they self-organized into luminal structures representative of the fallopian tube architecture with ciliated and secretory components.…”

Section: Other 3d Models Of the Ovarian Cancer Tmementioning

confidence: 99%

Organotypic 3D Models of the Ovarian Cancer Tumor Microenvironment

Watters

Bajwa

Kenny

2018

Cancers

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Ovarian cancer progression involves multifaceted and variable tumor microenvironments (TMEs), from the in situ carcinoma in the fallopian tube or ovary to dissemination into the peritoneal cavity as single cells or spheroids and attachment to the mesothelial-lined surfaces of the omentum, bowel, and abdominal wall. The TME comprises the tumor vasculature and lymphatics (including endothelial cells and pericytes), in addition to mesothelial cells, fibroblasts, immune cells, adipocytes and extracellular matrix (ECM) proteins. When generating 3D models of the ovarian cancer TME, researchers must incorporate the most relevant stromal components depending on the TME in question (e.g., early or late disease). Such complexity cannot be captured by monolayer 2D culture systems. Moreover, immortalized stromal cell lines, such as mesothelial or fibroblast cell lines, do not always behave the same as primary cells whose response in functional assays may vary from donor to donor; 3D models with primary stromal cells may have more physiological relevance than those using stromal cell lines. In the current review, we discuss the latest developments in organotypic 3D models of the ovarian cancer early metastatic microenvironment. Organotypic culture models comprise two or more interacting cell types from a particular tissue. We focus on organotypic 3D models that include at least one type of primary stromal cell type in an ECM background, such as collagen or fibronectin, plus ovarian cancer cells. We provide an overview of the two most comprehensive current models—a 3D model of the omental mesothelium and a microfluidic model. We describe the cellular and non-cellular components of the models, the incorporation of mechanical forces, and how the models have been adapted and utilized in functional assays. Finally, we review a number of 3D models that do not incorporate primary stromal cells and summarize how integration of current models may be the next essential step in tackling the complexity of the different ovarian cancer TMEs.

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Section: Other 3d Models Of the Ovarian Cancer Tmementioning

confidence: 99%

Organotypic 3D Models of the Ovarian Cancer Tumor Microenvironment

Watters

Bajwa

Kenny

2018

Cancers

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“…Brain organoids Modeling autism disorder [14] Modeling ALS disease [15] Modeling Parkinson's disease [16] Modeling Zika virus infection [17] Modeling Seckel syndrome [18] Brain-region specific organoids Modeling Zika virus infection and human brain development disease [19] Breast organoid Breast cancer research [20] Cystic organoids Modeling Alagille syndrome, polycyctic liver disease and cystic fibrosis [21] Fallopian tube organoids Ovarian cancer research [22] Liver bud Organ-bud transplantation for regenerative medicine [23] Lung organoids Lung development and lung disease modeling [22,25] Pancreas Pancreatic disease model [26] Retinal organoids Modeling glaucoma [27] Table 1. Summary of hiPSC-and ESC-derived organoids, adapted from Shi et al [1].…”

Section: Ipsc Derived Organoid Modelmentioning

confidence: 99%

“…Yucer et al [22] developed a hiPSC-derived 3D human FTE model, mimicking the FTE development process via various intermediate stages toward mature FTE in 3D organoid culture. Female reproductive tract structures including fallopian tube epithelium arise from the Müllerian duct in parallel to the urinary system from IM of the urogenital ridge in the posterior primitive streak.…”

Section: Fallopian Tubementioning

confidence: 99%

“…Female reproductive tract structures including fallopian tube epithelium arise from the Müllerian duct in parallel to the urinary system from IM of the urogenital ridge in the posterior primitive streak. Therefore, Yucer et al [22] recapitulated Müllerian development starting with IM generation and further developed into fallopian tube epithelial precursors using pro-Müllerian growth factors. Each step of this differentiation is monitored through the expression of established markers (Figure 7).…”

Section: Fallopian Tubementioning

confidence: 99%

“…Each step of this differentiation is monitored through the expression of established markers (Figure 7). Further differentiation of the fallopian tube epithelial lineage was attained on a 3D growth platform, which enables the FTE organoid to self-organize into a convoluted luminal structure with secretory and ciliated cellular components [22].…”

Section: Fallopian Tubementioning

confidence: 99%

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hiPSC-Based Tissue Organoid Regeneration

Qu¹,

Yucer²,

Garcia³

et al. 2018

Tissue Regeneration

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Induced pluripotent stem cells (iPSCs) are generated from terminally differentiated cells and have the potential to differentiate to any organs originated from the embryonic germ layers. Extensive effort has been made to establish protocols for direct in vitro conversion of human iPSCs (hiPSCs) to different cell types/organs. Importantly, hiPSCs can be generated from patients with known genetic mutations that predispose to high-risks of specific disease development. Thus, the hiPSCs technology provides unlimited resources for creating patient-specific disease models. hiPSC-derived three-dimensional "organoid" models have recently emerged as a powerful tool to recapitulate the physiologically-relevant process of disease progression in vitro. In this chapter, we will discuss the current advancement of organoid regeneration from hiPSCs and the applications of hiPSCs-derived organoids. The limitations and challenges of this approach will also be discussed here.

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Historical evolution of spheroids and organoids, and possibilities of use in life sciences and medicine

Sakalem

Síbio

Costa

et al. 2021

Biotechnology Journal

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Background: An impressive percentage of biomedical advances were achieved through animal research and cell culture investigations. For drug testing and disease researches, both animal models and preclinical trials with cell cultures are extremely important, but present some limitations, such as ethical concern and inability of representing complex tissues and organs. 3D cell cultures arise providing a more realistic in vitro representation of tissues and organs. Environment and cell type in 3D cultures can represent in vivo conditions and thus provide accurate data on cell-to-cell interactions, and cultivation techniques are based on a scaffold, usually hydrogel or another polymeric material, or without scaffold, such as suspended microplates, magnetic levitation, and microplates for spheroids with ultra-low fixation coating. Purpose and scope:This review aims at presenting an updated summary of the most common 3D cell culture models available, as well as a historical background of their establishment and possible applications. Summary:Even though 3D culturing is incapable of replacing other current research types, they will continue to substitute some unnecessary animal experimentation, as well as complement monolayer cultures. Conclusion:In this aspect, 3D culture emerges as a valuable alternative to the investigation of functional, biochemical, and molecular aspects of human pathologies.

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Directed Differentiation of Human Induced Pluripotent Stem Cells into Fallopian Tube Epithelium

Cited by 61 publications

References 36 publications

Organotypic 3D Models of the Ovarian Cancer Tumor Microenvironment

Organotypic 3D Models of the Ovarian Cancer Tumor Microenvironment

hiPSC-Based Tissue Organoid Regeneration

Historical evolution of spheroids and organoids, and possibilities of use in life sciences and medicine

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