Toward Organs on Demand: Breakthroughs and Challenges in Models of Organogenesis

Francipane, Maria Giovanna; Lagasse, Eric

doi:10.1007/s40139-016-0111-9

Cited by 12 publications

(14 citation statements)

References 72 publications

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“…Recent discoveries about how cells self‐organize are driving the creation of organ models for research or transplantation. Different artificial means, such as matrix molecules, silk films, and chips, among others, are being exploited to generate three‐dimensional structures from tissue‐specific stem cells, embryonic stem cells, and induced pluripotent stem cells (Francipane & Lagasse, ). These culture systems allow the researcher to address specific questions concerning how the intricate processes of development, homeostasis, and disease unfold and open up new avenues for regenerative medicine as well as disease correction (Xu et al, ).…”

Section: Overviewmentioning

confidence: 99%

Kidney‐in‐a‐lymph node: A novel organogenesis assay to model human renal development and test nephron progenitor cell fates

Francipane

Han

Oxburgh

et al. 2019

J Tissue Eng Regen Med

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Stem cell‐derived organoids are emerging as sophisticated models for studying development and disease and as potential sources for developing organ substitutes. Unfortunately, although organoids containing renal structures have been generated from mouse and human pluripotent stem cells, there are still critical unanswered questions that are difficult to attain via in vitro systems, including whether these nonvascularized organoids have a stable and physiologically relevant phenotype or whether a suitable transplantation site for long‐term in vivo studies can be identified. Even orthotopic engraftment of organoid cultures in the adult does not provide an environment conducive to vascularization and functional differentiation. Previously, we showed that the lymph node offers an alternative transplantation site where mouse metanephroi can differentiate into mature renal structures with excretory, homeostatic, and endocrine functions. Here, we show that the lymph node lends itself well as a niche to also grow human primary kidney rudiments and can additionally be viewed as a platform to interrogate emerging renal organoid cultures. Our study has a wide‐ranging impact for tissue engineering approaches to rebuild functional tissues in vivo including—but not limited to—the kidney.

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Section: Overviewmentioning

confidence: 99%

Kidney‐in‐a‐lymph node: A novel organogenesis assay to model human renal development and test nephron progenitor cell fates

Francipane

Han

Oxburgh

et al. 2019

J Tissue Eng Regen Med

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“…Many initiatives have been undertaken to increase organ donations and better usage of the donated organs [ 24 – 26 ]. One solution is the advent of laboratory-grown tissues, humanized animal organs, and bioartificial organs [ 27 , 28 ]. Regenerative medicine may help in solving some of these challenges [ 29 , 30 ].…”

Section: Introductionmentioning

confidence: 99%

Advances in Regenerative Medicine and Tissue Engineering: Innovation and Transformation of Medicine

Dzobo

Thomford

Senthebane

et al. 2018

Stem Cells International

306

223

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Humans and animals lose tissues and organs due to congenital defects, trauma, and diseases. The human body has a low regenerative potential as opposed to the urodele amphibians commonly referred to as salamanders. Globally, millions of people would benefit immensely if tissues and organs can be replaced on demand. Traditionally, transplantation of intact tissues and organs has been the bedrock to replace damaged and diseased parts of the body. The sole reliance on transplantation has created a waiting list of people requiring donated tissues and organs, and generally, supply cannot meet the demand. The total cost to society in terms of caring for patients with failing organs and debilitating diseases is enormous. Scientists and clinicians, motivated by the need to develop safe and reliable sources of tissues and organs, have been improving therapies and technologies that can regenerate tissues and in some cases create new tissues altogether. Tissue engineering and/or regenerative medicine are fields of life science employing both engineering and biological principles to create new tissues and organs and to promote the regeneration of damaged or diseased tissues and organs. Major advances and innovations are being made in the fields of tissue engineering and regenerative medicine and have a huge impact on three-dimensional bioprinting (3D bioprinting) of tissues and organs. 3D bioprinting holds great promise for artificial tissue and organ bioprinting, thereby revolutionizing the field of regenerative medicine. This review discusses how recent advances in the field of regenerative medicine and tissue engineering can improve 3D bioprinting and vice versa. Several challenges must be overcome in the application of 3D bioprinting before this disruptive technology is widely used to create organotypic constructs for regenerative medicine.

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“…Over the last decade, numerous approaches have been developed to culture and investigate cellular function in a three-dimensional (3D) environment. [1][2][3][4][5][6][7][8][9] In parallel, the adoption of human induced pluripotent stem cells (HiPSCs), for both basic research and drug discovery, is increasing (see Part 1 of this review). Since 3D culture systems provide a more natural tissue environment to study cell function-and patient-derived HiPSCs can model human disease pathophysiology better than most animal or other model systems-the use of HiPSC differentiated cell types in 3D culture systems provides numerous advantages: (1) study tissue and organ complexity in vivo; (2) provide the potential to be experimentally tractable, notably for compound screening; and (3) allow patient-specific responses, prior to clinical evaluation, to be monitored.…”

Section: Introductionmentioning

confidence: 99%

“…Since 3D culture systems provide a more natural tissue environment to study cell function-and patient-derived HiPSCs can model human disease pathophysiology better than most animal or other model systems-the use of HiPSC differentiated cell types in 3D culture systems provides numerous advantages: (1) study tissue and organ complexity in vivo; (2) provide the potential to be experimentally tractable, notably for compound screening; and (3) allow patient-specific responses, prior to clinical evaluation, to be monitored. 1 Organoid is a term that generally refers to an ex vivo cell culture, 2,7,8 derived from stem cells (although primary cells can also be employed, as in the case of cancer cells), that is self-organized and retains the functional architecture of the tissue in vivo and that can be maintained in culture for long periods of time. 3D cell cultures therefore provide a cellular microenvironment that better mimics conditions in vivo than more commonly employed two-dimensional (2D) cell culture systems.…”

Section: Introductionmentioning

confidence: 99%

Human iPS Cell-Derived Patient Tissues and 3D Cell Culture Part 2: Spheroids, Organoids, and Disease Modeling

Eglen

Reisine

2019

SLAS Technology

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Human induced pluripotent stem cells (HiPSCs) provide several advantages for drug discovery, but principally they provide a source of clinically relevant tissue. Furthermore, the use of HiPSCs cultured in three-dimensional (3D) systems, as opposed to traditional two-dimensional (2D) culture approaches, better represents the complex tissue architecture in vivo. The use of HiPSCs in 3D spheroid and organoid culture is now growing, but particularly when using myocardial, intestinal enteric nervous system, and retinal cell lines. However, organoid cell culture is perhaps making the most notable impact in research and drug discovery, in which 3D neuronal cell cultures allow direct modeling of cortical cell layering and neuronal circuit activity. Given the specific degeneration seen in discrete neuronal circuitry in Alzheimer's disease (AD) and Parkinson's disease (PD), HiPSC culture systems are proving to be a major advance. In the present review, the second part of a two-part review, we discuss novel methods in which 3D cell culture systems (principally organoids) are now being used to provide insights into disease mechanisms. (The use of HiPSCs in target identification was reviewed in detail in Part 1.)

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Toward Organs on Demand: Breakthroughs and Challenges in Models of Organogenesis

Cited by 12 publications

References 72 publications

Kidney‐in‐a‐lymph node: A novel organogenesis assay to model human renal development and test nephron progenitor cell fates

Kidney‐in‐a‐lymph node: A novel organogenesis assay to model human renal development and test nephron progenitor cell fates

Advances in Regenerative Medicine and Tissue Engineering: Innovation and Transformation of Medicine

Human iPS Cell-Derived Patient Tissues and 3D Cell Culture Part 2: Spheroids, Organoids, and Disease Modeling

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