Design Principles for Pluripotent Stem Cell-Derived Organoid Engineering

Silva, Teresa P; Cotovio, João P.; Bekman, Evguenia; Carmo‐Fonseca, Maria; Fernandes, Tiago G.

doi:10.1155/2019/4508470

Cited by 32 publications

(27 citation statements)

References 189 publications

(205 reference statements)

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“…Microenvironmental cues include biochemical and biophysical (oxygen tension, ECM stiffness, and fluid flow) signals during organogenesis regulate cell behavior of different stem cell populations (Vining and Mooney, 2017;Silva et al, 2019). The ECM of the kidney is a complex architectural network that contains collagens, elastin, and several proteoglycans and glycoproteins, which together form basal membranes and the interstitial space.…”

Section: Microenvironmental Cuesmentioning

confidence: 99%

Cellular and Molecular Mechanisms of Kidney Development: From the Embryo to the Kidney Organoid

Rad

Aghdami

Moghadasali

2020

Front. Cell Dev. Biol.

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Development of the metanephric kidney is strongly dependent on complex signaling pathways and cell-cell communication between at least four major progenitor cell populations (ureteric bud, nephron, stromal, and endothelial progenitors) in the nephrogenic zone. In recent years, the improvement of human-PSC-derived kidney organoids has opened new avenues of research on kidney development, physiology, and diseases. Moreover, the kidney organoids provide a three-dimensional (3D) in vitro model for the study of cell-cell and cell-matrix interactions in the developing kidney. In vitro recreation of a higher-order and vascularized kidney with all of its complexity is a challenging issue; however, some progress has been made in the past decade. This review focuses on major signaling pathways and transcription factors that have been identified which coordinate cell fate determination required for kidney development. We discuss how an extensive knowledge of these complex biological mechanisms translated into the dish, thus allowed the establishment of 3D human-PSC-derived kidney organoids.

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Section: Microenvironmental Cuesmentioning

confidence: 99%

Cellular and Molecular Mechanisms of Kidney Development: From the Embryo to the Kidney Organoid

Rad

Aghdami

Moghadasali

2020

Front. Cell Dev. Biol.

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“…Today, scientists can generate organoids from a variety of different cell sources, but some design principles must be taken into consideration when generating an organoid: (1) biophysical properties-the use of solid ECMs to entrap the organoids, or the use of a scaffold-free approach; (2) self-governing of organoid formation-exclusive dependence on endogenous signals or dependence on the addition of exogenous cues; (3) starting cell population-derivation from a single cell, from a homogeneous cell population, or from a co-culture of different cell types [10]. Besides these, recent engineering approaches have been developed to increase the complexity of human organoids and PSCs play an important role in this matter [10,81].…”

Section: Production Of Liver Organoids From Human Pluripotent Stem Cellsmentioning

confidence: 99%

Production of Human Pluripotent Stem Cell-Derived Hepatic Cell Lineages and Liver Organoids: Current Status and Potential Applications

Cotovio

Fernandes

2020

Bioengineering

Self Cite

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Liver disease is one of the leading causes of death worldwide, leading to the death of approximately 2 million people per year. Current therapies include orthotopic liver transplantation, however, donor organ shortage remains a great challenge. In addition, the development of novel therapeutics has been limited due to the lack of in vitro models that mimic in vivo liver physiology. Accordingly, hepatic cell lineages derived from human pluripotent stem cells (hPSCs) represent a promising cell source for liver cell therapy, disease modelling, and drug discovery. Moreover, the development of new culture systems bringing together the multiple liver-specific hepatic cell types triggered the development of hPSC-derived liver organoids. Therefore, these human liver-based platforms hold great potential for clinical applications. In this review, the production of the different hepatic cell lineages from hPSCs, including hepatocytes, as well as the emerging strategies to generate hPSC-derived liver organoids will be assessed, while current biomedical applications will be highlighted.

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“…50,51 Gradients of morphogens can be established by microfluidics or microfabrication on the micro-or nanometer scale 52,53 and combined with an engineered ECM expressing specific nanotopography or through 3D (bio) printing. [54][55][56] However, one should be careful with designing biomaterials or matrices of poorly defined composition, heterogeneous nature, and batch-to-batch variability, which could inhibit the process of self-organization.…”

Section: Engineered Microenvironmentmentioning

confidence: 99%

Building Complex Life Through Self-Organization

Sthijns¹,

LaPointe²,

Blitterswijk³

2019

Tissue Engineering Part A

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Cells are inherently conferred with the ability to self-organize into the tissues and organs comprising the human body. Self-organization can be recapitulated in vitro and recent advances in the organoid field are just one example of how we can generate small functioning elements of organs. Tissue engineers can benefit from the power of self-organization and should consider how they can harness and enhance the process with their constructs. For example, aggregates of stem cells and tissue-specific cells benefit from the input of carefully selected biomolecules to guide their differentiation toward a mature phenotype. This can be further enhanced by the use of technologies to provide a physiological microenvironment for self-organization, enhance the size of the constructs, and enable the long-term culture of self-organized structures. Of importance, conducting selforganization should be limited to fine-tuning and should avoid over-engineering that could counteract the power of inherent cellular self-organization.Self-organization is a powerful innate feature of cells that can be fine-tuned but not over-engineered to create new tissues and organs.

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Design Principles for Pluripotent Stem Cell-Derived Organoid Engineering

Cited by 32 publications

References 189 publications

Cellular and Molecular Mechanisms of Kidney Development: From the Embryo to the Kidney Organoid

Cellular and Molecular Mechanisms of Kidney Development: From the Embryo to the Kidney Organoid

Production of Human Pluripotent Stem Cell-Derived Hepatic Cell Lineages and Liver Organoids: Current Status and Potential Applications

Building Complex Life Through Self-Organization

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