Scaffolding kidney organoids on silk

Gupta, Ashwani; Coburn, Jeannine M.; Davis‐Knowlton, Jessica; Kimmerling, Erica P.; Kaplan, David L.; Oxburgh, Leif

doi:10.1002/term.2830

Cited by 40 publications

(39 citation statements)

References 36 publications

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“…The development of the intestinal organoid system in 2009 was a major technological advance for the stem cell organoids field. Since then, an extensive body of works have improved the methodology and expanded the range of tissue and organ types that can be investigated, such as brain, gastric intestine, liver, kidney, lung, pancreas, prostate, retina, cardic, blood vessel, and mammary gland . Their versatile nature and potential to generate human tissues endow organoids with a variety of applications.…”

Section: Hydrogels In Organoids Formationmentioning

confidence: 99%

“…Actually, hydrogels served as scaffolds have paved a new way for engineering kidney organoids by precisely controlling the extracellular microenvironment, making it possible to guide the organization of kidney organoids. In one study, silk fibroin was used as scaffolds to support the growth and differentiation of hiPSC‐derived kidney organoids . Silk has been widely used to support growth of cornea, gastrointestinal tissues, and neural tissue due to its properties of biocompatibility, safety and adjustable degradability and its ability to be modified by incorporation of macromolecules.…”

Section: Hydrogels In Organoids Formationmentioning

confidence: 99%

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Advances in Hydrogels in Organoids and Organs‐on‐a‐Chip

et al. 2019

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The major motivation is to better mimic human physiology and functions at multiscales from the molecular to the cellular, tissue, organ or even whole organism level. Current model systems primarily rely on the monolayer cell cultures and animal models. Simplistic monolayer cultures have their advantages, but they are often significantly different in gene expression, epigenetics, and cell function compared to native 3D tissues. [1,2] Also, they often lack cell-cell and cell-matrix interactions, [2,3] leading to the absence of tissue specific properties. Although animal models are widely used in biomedical research, they fail to faithfully predict human responses in a physiologically relevant manner due to the significant species divergences. [4] The limitations of these systems have provided an impetus for the development of alternative cell-based 3D models in vitro that better resemble the complex functionalities of living organs. Over the last several years, organoids and organ-on-a-chip (OOC), representing the major technological breakthrough, have emerged as two distinct model systems to achieve the same goal of building 3D organotypic models in vitro by bridging the gap between animal models and monolayer cultures. These engineered models are different in terms of cell source, tissue composition, architectural variability, functional features, scales, cellular fidelity, etc. Organoids, primarily evolving from developmental principles, refer to 3D multicellular tissues by self-organization of stem cells or organ-specific progenitors, which can recapitulate the intricate architectures and functionalities of in vivo organs. [5][6][7] Recent breakthroughs in organoid technology have enabled the successful generation of a variety of human organoids, such as the brain, [8,9] intestine, [10,11] liver, [12] kidney, [13,14] lung, [15] etc. These near physiological 3D organoids have garnered momentum for their potential applications in human organ development and disease modeling, drug screening and regenerative medicine. The explosion of organoids research has been catalyzed by the significant progress of stem cell biology and availability of human stem cells. In contrast, the OOC, relying on the bioengineering design principle, is a miniaturized in vitro model that can recreate the functional units of living organs on a microfluidic cell culture device using predifferentiated cells, often cell lines. [1,16] The OOC is primarily evolved from the convergence of tissue engineering and microfabricated technologies, which is characterized by the capability to simulate cellular microenvironment by precise control over fluid flow, mechanical forces and biochemical factors. [4,17] Remarkable progress has been made Significant advances in materials, microscale technology, and stem cell biology have enabled the construction of 3D tissues and organs, which will ultimately lead to more effective diagnostics and therapy. Organoids and organs-on-a-chip (OOC), evolved from developmental biology and bioengineering principles, have e...

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Section: Hydrogels In Organoids Formationmentioning

confidence: 99%

Section: Hydrogels In Organoids Formationmentioning

confidence: 99%

Advances in Hydrogels in Organoids and Organs‐on‐a‐Chip

et al. 2019

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“…The mix of cells resulting from directed differentiation is predicted to contain either no or only a very small number of progenitors for the collecting duct system (Islam and Nishinakamura, 2019), which is known to serve as the inducer of nephron epithelium differentiation (Carroll et al, 2005). In prior experiments we have provided the Wnt stimulus that induces mesenchyme-to-epithelium transition through treatment with the small molecule GSK3 inhibitor CHIR 99021 (Brown et al, 2015; Gupta et al, 2019). However, in a series of titrations aimed at determining the dose of CHIR to use to initiate directed differentiation of WTC11 iPSCs to kidney progenitors, spontaneous epithelial differentiation can be seen at day 9 of the directed differentiation, prior to detachment of cells and organoid formation (Fig.…”

Section: Resultsmentioning

confidence: 99%

Asynchronous mixing of kidney progenitor cells potentiates nephrogenesis in organoids

Gupta

Sarkar

Pan

et al. 2019

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Recent years have seen rapid advances in directed differentiation of human pluripotent stem cells (PSCs) to kidney cells. However, a fundamental difficulty in emulating kidney tissue formation is that kidney development is iterative. Recent studies argue that the human nephron forms through gradual contribution of nephron progenitor cells whose differentiation fates depend on the time at which they are recruited. We show that the majority of PSC-derived nephron progenitor cells differentiated in a short wave in organoid formation and to improve fidelity of PSC-derived organoids, we emulated the asynchronous mix found in the fetal kidney by combining cells differentiated at different times in the same organoid. Asynchronous mixing promoted nephrogenesis, and lineage marking data showed that proximal and distal nephron components preferentially derive from cell populations differentiated at distinct times. When engrafted under the kidney capsule these heterochronic organoids were vascularized and displayed essential features of kidney tissue. Micro-CT and injection of a circulating vascular marker demonstrated that engrafted kidney tissue was connected to the systemic circulation by 2 weeks after engraftment. Proximal tubule glucose uptake was confirmed using intravenous injection of fluorescent dextran. Despite these promising measures of graft function, overgrowth of stromal cells prevented long-term study, and we propose that this is a technical feature of the engraftment procedure rather than a specific shortcoming of the directed differentiation because kidney organoids derived from primary cells and whole embryonic kidneys develop the same stromal overgrowth when engrafted under the kidney capsule.

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“…What is possible outside of the embryo is to modify culture format to optimize such models for one or other application, even when this does not necessarily involve creating a perfect model of the developing organ. A variety of studies have now claimed improvements in scale up or relative maturation, including the use of dis-tinct culture formats and changes in culture materials (Table 2; Cruz et al 2017;Czerniecki et al 2018;Przepiorski et al 2018;Garreta et al 2019;Gupta et al 2019;Kumar et al 2019). In addition, protocols for the generation of specific renal cell subtypes, such as podocyte or collecting duct epithelium, are being reported (Musah et al 2017;Taguchi and Nishinakamura 2017;Hale et al 2018;Yoshimura et al 2019).…”

Section: Other Points Of Divergence Between Developing Organ and Orgamentioning

confidence: 99%

“…In addition, protocols for the generation of specific renal cell subtypes, such as podocyte or collecting duct epithelium, are being reported (Musah et al 2017;Taguchi and Nishinakamura 2017;Hale et al 2018;Yoshimura et al 2019). Finally, a variety of approaches have now been proposed to improve vascularization in vitro (Homan et al 2019) or provide vascular flow in vivo (Sharmin et al 2016;Bantounas et al 2018;van den Berg et al 2018;Garreta et al 2019;Gupta et al 2019). In most instances, these involve modifications of prior differentiation protocols (Table 2; Taguchi et al 2014;Freedman et al 2015;Morizane et al 2015;.…”

Section: Other Points Of Divergence Between Developing Organ and Orgamentioning

confidence: 99%

Kidney organoids: accurate models or fortunate accidents

2019

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There are now many reports of human kidney organoids generated via the directed differentiation of human pluripotent stem cells (PSCs) based on an existing understanding of mammalian kidney organogenesis. Such kidney organoids potentially represent tractable tools for the study of normal human development and disease with improvements in scale, structure, and functional maturation potentially providing future options for renal regeneration. The utility of such organotypic models, however, will ultimately be determined by their developmental accuracy. While initially inferred from mouse models, recent transcriptional analyses of human fetal kidney have provided greater insight into nephrogenesis. In this review, we discuss how well human kidney organoids model the human fetal kidney and how the remaining differences challenge their utility.

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Scaffolding kidney organoids on silk

Cited by 40 publications

References 36 publications

Advances in Hydrogels in Organoids and Organs‐on‐a‐Chip

Advances in Hydrogels in Organoids and Organs‐on‐a‐Chip

Asynchronous mixing of kidney progenitor cells potentiates nephrogenesis in organoids

Kidney organoids: accurate models or fortunate accidents

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