3D heterogeneous islet organoid generation from human embryonic stem cells using a novel engineered hydrogel platform

Candiello, Joseph; Grandhi, Taraka Sai Pavan; Goh, Saik Kia; Vaidya, Vimal; Lemmon-Kishi, Maya; Eliato, Kiarash Rahmani; Ros, Robert; Kumta, Prashant N.; Rege, Kaushal; Banerjee, Ipsita

doi:10.1016/j.biomaterials.2018.05.031

Cited by 123 publications

(116 citation statements)

References 57 publications

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“…In another case, PEG‐based hydrogels covalently functionalized with laminin 1 were demonstrated to support the expansion of pancreas progenitors within the 3D scaffold, whereas the organoids did not expand and gradually lost their pancreatic and epithelial characters in PEG hydrogels without laminin functionalization, indicating the necessity of integrin engagement . In addition, Amikagel, composed of the commercial product Amikacin and the crosslinker PEGDE, has been developed to engineer heterogeneous islet organoids with precise size and endocrine function . Moreover, the specific PEGDE to Amikacin ratio bears appropriate hydroxyl group moieties that may be beneficial to promote self‐assembly.…”

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 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%

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

et al. 2019

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“…To date, these multicellular systems have been increasingly employed in advanced bottom‐up engineering of numerous tissue types such as kidney, liver, or pancreas. In fact, researchers have been recently able to develop pancreatic islet organoids from human embryonic stem cell derived pancreatic progenitor cells . The cells spontaneously aggregated in vitro under controlled culture conditions and formed robust multicellular spheroid‐shaped organoids with controlled size and cellular heterogeneity.…”

Section: Cell‐rich Assembliesmentioning

confidence: 99%

“…Upon maturation the resulting 3D organoids exhibited functional insulin secretion after a glucose challenge. It is important to emphasize that such organoids were assembled using a unique hydrogel platform (i.e., Amikagel) and that the development of biofunctional organoids in fully scaffold‐free conditions remains to be demonstrated to the best of our knowledge . There is no doubt that these are highly promising microphysiological constructs, however most in vitro generated organoids still generally lack key cellular constituents of the tissues they aim to recapitulate.…”

Section: Cell‐rich Assembliesmentioning

confidence: 99%

Advanced Bottom‐Up Engineering of Living Architectures

et al. 2019

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Bottom‐up tissue engineering is a promising approach for designing modular biomimetic structures that aim to recapitulate the intricate hierarchy and biofunctionality of native human tissues. In recent years, this field has seen exciting progress driven by an increasing knowledge of biological systems and their rational deconstruction into key core components. Relevant advances in the bottom‐up assembly of unitary living blocks toward the creation of higher order bioarchitectures based on multicellular‐rich structures or multicomponent cell–biomaterial synergies are described. An up‐to‐date critical overview of long‐term existing and rapidly emerging technologies for integrative bottom‐up tissue engineering is provided, including discussion of their practical challenges and required advances. It is envisioned that a combination of cell–biomaterial constructs with bioadaptable features and biospecific 3D designs will contribute to the development of more robust and functional humanized tissues for therapies and disease models, as well as tools for fundamental biological studies.

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“…In contrast, 3D islet-like organoids generated from either human embryonic stem cells [50] or from spontaneously formed endocrine cell clusters produced by stepwise differentiation of human PSCs [51] released insulin in response to glucose in vitro and in vivo. More recent efforts have introduced synthetic hydrogels [52] or co-cultures with HUVECs and mesenchymal stem cells (MSCs) combined with a self-condensation system [53]. These more advanced systems produced islet organoids with increased complexity and maturity, including endothelial cells and vascularisation.…”

Section: Don't Believe the Hype: Organoid Limitationsmentioning

confidence: 99%

Diabetes through a 3D lens: organoid models

2020

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Diabetes is one of the most challenging health concerns facing society. Available drugs treat the symptoms but there is no cure. This presents an urgent need to better understand human diabetes in order to develop improved treatments or target remission. New disease models need to be developed that more accurately describe the pathology of diabetes. Organoid technology provides an opportunity to fill this knowledge gap. Organoids are 3D structures, established from pluripotent stem cells or adult stem/progenitor cells, that recapitulate key aspects of the in vivo tissues they mimic. In this review we briefly introduce organoids and their benefits; we focus on organoids generated from tissues important for glucose homeostasis and tissues associated with diabetic complications. We hope this review serves as a touchstone to demonstrate how organoid technology extends the research toolbox and can deliver a step change of discovery in the field of diabetes.

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3D heterogeneous islet organoid generation from human embryonic stem cells using a novel engineered hydrogel platform

Cited by 123 publications

References 57 publications

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

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

Advanced Bottom‐Up Engineering of Living Architectures

Diabetes through a 3D lens: organoid models

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