A reduction of primary cilia but not hedgehog signaling disrupts morphogenesis in testicular organoids

Goldsmith, Taylor; Sakib, Sadman; Webster, Dennis A.; Carlson, Daniel F.; Hoorn, Frans van der; Dobrinski, Ina

doi:10.1007/s00441-019-03121-8

Cited by 14 publications

(6 citation statements)

References 34 publications

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“…In one study, gene editing with the outer dense fiber protein 2 (ODF2) and siRNA knockdown of intraflagellar transport 88 (IFT88) significantly reduced the number and length of cilia on cells in testicular organoids, resulting in irregular cellular assembly. [159] In retinal organoids, CRISPR/ Cas9 was used to createretinoblastoma 1 (RB1) null hESCs, which were subsequently used to form organoids. Compared to isogenic wild-type controls, RB1 null organoids showed significantly lower bipolar cells, photoreceptor cells, and ganglion cells population.…”

Section: Gene Editing For Studying Organogenesismentioning

confidence: 99%

Bioengineering Approaches for the Advanced Organoid Research

Zhang

Rathnam

et al. 2021

Advanced Materials

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organoids should exhibit essential features, including organ-specific multiple cell types, functions of the organ, and spatially organized structures. The emergence and progression of organoid technologies have resulted from several important discoveries (Figure 1). The formation of actual tissuelike colonies in vitro was firstly observed from a co-culture system of keratinocytes and 3T3 fibroblasts. [4] Self-organization, one of the fundamental aspects of organogenesis, was first observed via two distinct approaches, namely reaggregation and structural patterning of dissociated single cells. [5,6] The establishment of 3D culture methods for the structural organization began with the development of extracellular matrices (ECM).In the late 1980s, Bissell and colleagues observed that a laminin-rich gel could function as a basement membrane to differentiate and morphogenesis of mammary epithelial cells. [7,8] In the 1990s, it was reported that in addition to their primary role in physical support, ECM components could regulate gene expression by interacting with integrin-based focal adhesion pathways. [9] Finally, in 2009, Clevers group reported that embedding single intestinal stem cells in ECM substitute had created crypt-like structures similar to the epithelium of the native intestinal tissues, which were the first organoids. [10] Based on these recognitions, biochemical cues that include the initiation of lineage-specific genetic programs have been incorporated in 3D organoid cultures. Through exposure to morphogens, growth factors, or morphogen inhibitors, multiple research groups rapidly developed various organoid models using embryonic stem cells (ESCs) or adult stem cells (ASCs); these include intestine, [10] stomach, [11] liver, [12] pancreas, [13] prostate, [14] and brain [15] organoids. At the same time, vascularization techniques were devised by several groups to embody microenvironments that are physiologically close to their actual counterparts. Microfluidic systems, [16] endothelial cell-coated modules, [17] and vascular endothelial growth factor delivery systems [18] have been demonstrated as in vitro vasculature systems that can facilitate oxygen or nutrients transport to the inner mass of organoids.In the late 2010s, owing to the accumulated information on mechanisms underlying organogenesis and the remarkable advancements in the fields of biomaterial and bioengineering, the era of "organoid customization" has begun. Customizable hydrogel matrices have been proposed to form intestinal organoids whose internal networks recapitulate the Recent advances in 3D cell culture technology have enabled scientists to generate stem cell derived organoids that recapitulate the structural and functional characteristics of native organs. Current organoid technologies have been striding toward identifying the essential factors for controlling the processes involved in organoid development, including physical cues and biochemical signaling. There is a growing demand for engineering dynamic niches characterized by ...

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Section: Gene Editing For Studying Organogenesismentioning

confidence: 99%

Bioengineering Approaches for the Advanced Organoid Research

Zhang

Rathnam

et al. 2021

Advanced Materials

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“…In mice, macaques, and human prepubertal testicular cells testicular organoids were developed and the 3D organization of the mammalian testis was obtained (Sakib, Uchida, et al, 2019). The protocol from Sakib and colleagues was used to study the testicular tubules morphogenesis and the role of Hedgehog signaling in primary cilia loss and in vitro morphogenesis in pigs (Goldsmith et al, 2020). Matrigel ® testicular culture has been highly implemented in rats (Alves-Lopes et al, 2017;Yu et al, 2005) and mice .…”

Section: Testismentioning

confidence: 99%

Organoids of the male reproductive system: Challenges, opportunities, and their potential use in fertility research

Patrício

Santiago

Mano

et al. 2022

WIREs Mechanisms of Disease

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Organoids are units of function of a given organ able to reproduce, in culture, a biological structure similar in architecture and function to its counterpart in vivo. Today, it is possible to develop an organoid from a fragment of tissue, a stem cell located in an adult organ, an embryonic stem cell, or an induced pluripotent stem cell. In the past decade, many organoids have been developed which mimic stomach, pancreas, liver and brain tissues, optic cups, among many others. Additionally, different male reproductive system organs have already been developed as organoids, including the prostate and testis. These 3D cultures may be of great importance for urological cancer research and have the potential to be used in fertility research for the study of spermatozoa production and maturation, germ cells–somatic cells interactions, and mechanisms of disease. They also provide an accurate preclinical pipeline for drug testing and discovery, as well as for the study of drug resistance. In this work, we revise the current knowledge on organoid technology and its use in healthcare and research, describe the male reproductive system organoids and other biomaterials already developed, and discuss their current application. Finally, we highlight the research gaps, challenges, and opportunities in the field and propose strategies to improve the use of organoids for the study of male infertility situations. This article is categorized under: Reproductive System Diseases > Stem Cells and Development Reproductive System Diseases > Biomedical Engineering

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“…Further investigations revealed the indirect involvement of PTCH-dependent-GLI1-independent, non-canonical Hh signalling in increasing the survival rate of cancer stem cells via cross-talk with Wnt signalling in patient-derived colon cancer organoids [ 300 ]. Moreover, the role of primary cilia, but not of canonical Hh signalling, in testicular morphogenesis has been confirmed in cyclopamine-treated organoids [ 301 ].…”

Section: Mechanobiological Design Opportunities For Modelling Hedgeho...mentioning

confidence: 99%

From mesenchymal niches to engineered in vitro model systems: Exploring and exploiting biomechanical regulation of vertebrate hedgehog signalling

Ghuloum

Johnson

Galdo

et al. 2022

Materials Today Bio

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A reduction of primary cilia but not hedgehog signaling disrupts morphogenesis in testicular organoids

Cited by 14 publications

References 34 publications

Bioengineering Approaches for the Advanced Organoid Research

Bioengineering Approaches for the Advanced Organoid Research

Organoids of the male reproductive system: Challenges, opportunities, and their potential use in fertility research

From mesenchymal niches to engineered in vitro model systems: Exploring and exploiting biomechanical regulation of vertebrate hedgehog signalling

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