Four challenges for organoid engineers

Davies, Jamie A.; Lawrence, Melanie L.

doi:10.1016/b978-0-12-812636-3.00014-6

Cited by 3 publications

(2 citation statements)

References 16 publications

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“…First, the kidney is a complex organ with over 20 different cell types, despite the organ being highly vascularized, which may be often perceived as an ideal target point for host recipients. Importantly, iPSC-derived cell progeny are generally small in size and difficult to detect for the purpose of transplantation (Davies & Lawrence, 2018). To aid in cell tracing, an administration technique that allows site-restricted tracing, for example, subcapsular transplantation of cells/tissue into the kidney is available (Sharmin et al, 2016).…”

Section: F I G U R E 5 Engraftment Into Host Newborn Kidneys Wasmentioning

confidence: 99%

Percutaneous intrarenal transplantation of differentiated induced pluripotent stem cells into newborn mice

Lau

Al-Rubaie

Saini

et al. 2020

The Anatomical Record

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The in vivo engraftment of induced pluripotent stem cell (iPSC)‐derived podocytes following allogeneic transplantation into host kidneys remains a challenge. Here we investigate the survival and engraftment of human dermal fibroblasts‐derived differentiated iPSCs using a newborn mouse model, which represents a receptive immunoprivileged host environment. iPSCs were generated from skin biopsies of patients using Sendai virus reprogramming. Differentiation of nephrin (NPHS1)‐green fluorescent protein (GFP) iPSCs into kidney podocytes (iPSC‐PODs) was performed by the addition of Activin A, bone morphogenetic protein 7 (BMP7), and retinoic acid over 10 days of culture. To assess the in vivo incorporation of cells, undifferentiated iPSCs or day 10 iPSC‐PODs, were labeled with either carboxyfluorescein succinimidyl ester (CFSE) or Qdot nanocrystals (Q705). Thereafter, 1 × 105 differentiated iPSC‐PODs were injected directly into the kidneys of mouse pups at postnatal day one (P1). Using co‐expression analysis of glomerular and podocyte‐specific markers, Day 10 differentiated iPSC‐PODs that were positive for podocin, were detected following direct kidney injection into newborn mice up to 1 week after transplantation. Undifferentiated iPSC‐PODs were not detected at the same timepoint. The transplanted cells were viable and located in the outer nephrogenic zone where they were found to colocalize with, or sit adjacent to, cells positive for glomerular‐specific markers including podocin, synaptopodin, and Wilms' tumor 1 (WT1). This study provides proof‐of‐principle that transplanted iPSC–POD can survive in recipient newborn mouse kidneys due to the immature and immunoprivileged nature of the developing postnatal kidneys.

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Section: F I G U R E 5 Engraftment Into Host Newborn Kidneys Wasmentioning

confidence: 99%

Percutaneous intrarenal transplantation of differentiated induced pluripotent stem cells into newborn mice

Lau

Al-Rubaie

Saini

et al. 2020

The Anatomical Record

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“…In addition to the described challenges in the assessment of function and structure of organoids, our ability to generate organoids from PSCs has also been subjected to some limitations [187]. Firstly, there is a need to produce a significant number of organoids to use in high-throughput applications, as well as larger organoids are required to better recapitulate the anatomy seen in human tissues.…”

Section: Conclusion and Future Challengesmentioning

confidence: 99%

Design Principles for Pluripotent Stem Cell-Derived Organoid Engineering

Silva

Cotovio

Bekman

et al. 2019

Stem Cells International

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Human morphogenesis is a complex process involving distinct microenvironmental and physical signals that are manipulated in space and time to give rise to complex tissues and organs. Advances in pluripotent stem cell (PSC) technology have promoted the in vitro recreation of processes involved in human morphogenesis. The development of organoids from human PSCs represents one reliable source for modeling a large spectrum of human disorders, as well as a promising approach for drug screening and toxicological tests. Based on the “self-organization” capacity of stem cells, different PSC-derived organoids have been created; however, considerable differences between in vitro-generated PSC-derived organoids and their in vivo counterparts have been reported. Advances in the bioengineering field have allowed the manipulation of different components, including cellular and noncellular factors, to better mimic the in vivo microenvironment. In this review, we focus on different examples of bioengineering approaches used to promote the self-organization of stem cells, including assembly, patterning, and morphogenesis in vitro, contributing to tissue-like structure formation.

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Organoid Technology: Current Standing and Future Perspectives

et al. 2021

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Organoids are powerful systems to facilitate the study of individuals' disorders and personalized treatments. This emerging technology has improved the chance of translatability of drugs for preclinical therapies and mimicking of the complexity of organs, proposing numerous approaches for human disease modeling, tissue engineering, drug development, diagnosis, and regenerative medicine. In this review, we outline the history of organoid technology and summarize its faithful applications, and then we discuss the challenges and limitations encountered by three-dimensional organoids. Finally, we propose that human organoids offer a basic mechanistic infrastructure for “human modeling” systems to prescribe personalized medicines.

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Four challenges for organoid engineers

Cited by 3 publications

References 16 publications

Percutaneous intrarenal transplantation of differentiated induced pluripotent stem cells into newborn mice

Percutaneous intrarenal transplantation of differentiated induced pluripotent stem cells into newborn mice

Design Principles for Pluripotent Stem Cell-Derived Organoid Engineering

Organoid Technology: Current Standing and Future Perspectives

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