Human iPSC-derived renal organoids engineered to report oxidative stress can predict drug-induced toxicity

ML, Lawrence; Elhendawi, Mona; M, Morlock; W, Liu; S, Liu; Palakkan, Anwar Azad; LF, Seidl; Hohenstein, Peter; AK, Sjögren; Ja, Davies

doi:10.1016/j.isci.2022.103884

Cited by 18 publications

(12 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Human kidney organoids made from induced pluripotent stem (iPS) cells have been used to model human development 46 , and to model some human kidney pathologies from patient-derived iPS cells 47 – 49 and from cells engineered to have genetic defects 48 . They have also been used to investigate critical pathways in renal repair 50 , and to model pathways of drug-induced nephrotoxicity 51 and to screen for and report nephrotoxicity fluorescently 52 . It is important to note, though, that there are differences between human and mouse development 53 and caution should be used in extrapolating from one to the other.…”

Section: Discussionmentioning

confidence: 99%

Production of kidney organoids arranged around single ureteric bud trees, and containing endogenous blood vessels, solely from embryonic stem cells

Palakkan

Tarnick

Waterfall

et al. 2022

Sci Rep

View full text Add to dashboard Cite

There is intense worldwide effort in generating kidney organoids from pluripotent stem cells, for research, for disease modelling and, perhaps, for making transplantable organs. Organoids generated from pluripotent stem cells (PSC) possess accurate micro-anatomy, but they lack higher-organization. This is a problem, especially for transplantation, as such organoids will not be able to perform their physiological functions. In this study, we develop a method for generating murine kidney organoids with improved higher-order structure, through stages using chimaeras of ex-fetu and PSC-derived cells to a system that works entirely from embryonic stem cells. These organoids have nephrons organised around a single ureteric bud tree and also make vessels, with the endothelial network approaching podocytes.

show abstract

Section: Discussionmentioning

confidence: 99%

Production of kidney organoids arranged around single ureteric bud trees, and containing endogenous blood vessels, solely from embryonic stem cells

Palakkan

Tarnick

Waterfall

et al. 2022

Sci Rep

View full text Add to dashboard Cite

show abstract

“…In addition, disease models using organoids have been constructed for a wide range of diseases, including Alzheimer’s [ 97 ], Parkinson’s [ 98 ], lung [ 99 ], and liver diseases [ 100 ]. Organoids are also used in the search for effective drugs for disease and toxicity tests [ 101 , 102 , 103 , 104 ]. Park et al created neural organoids from iPSC models derived from patients with Alzheimer’s disease and presented detailed strategies for drug screening [ 104 ].…”

Section: Novel Technology For Disease Modeling With Ipscsmentioning

confidence: 99%

Induced Pluripotent Stem Cell-Based Drug Screening by Use of Artificial Intelligence

2022

View full text Add to dashboard Cite

Induced pluripotent stem cells (iPSCs) are terminally differentiated somatic cells that differentiate into various cell types. iPSCs are expected to be used for disease modeling and for developing novel treatments because differentiated cells from iPSCs can recapitulate the cellular pathology of patients with genetic mutations. However, a barrier to using iPSCs for comprehensive drug screening is the difficulty of evaluating their pathophysiology. Recently, the accuracy of image analysis has dramatically improved with the development of artificial intelligence (AI) technology. In the field of cell biology, it has become possible to estimate cell types and states by examining cellular morphology obtained from simple microscopic images. AI can evaluate disease-specific phenotypes of iPS-derived cells from label-free microscopic images; thus, AI can be utilized for disease-specific drug screening using iPSCs. In addition to image analysis, various AI-based methods can be applied to drug development, including phenotype prediction by analyzing genomic data and virtual screening by analyzing structural formulas and protein–protein interactions of compounds. In the future, combining AI methods may rapidly accelerate drug discovery using iPSCs. In this review, we explain the details of AI technology and the application of AI for iPSC-based drug screening.

show abstract

“…For example, HMOX1 is a known marker of oxidative stress. Recently, investigators generated an iPSC HMOX1 reporter line, differentiated it into kidney organoids, and used this line for screening of a panel of blind-coded compounds for putative nephrotoxicants [55].…”

Section: Potential Role Of Gene Editing In Human Kidney Organoids And...mentioning

confidence: 99%

“…Most recently, kidney-on-a-chip models have been established using multiple cell populations from single donors [63], demonstrating their potential use in personalized medicine, as well as coupled with other organs-on-a-chip, as part of multi-organ models [64]. While the main focus of most studies utilizing kidney-on-a-chip technology thus far has been nephrotoxicity from drugs such as cisplatin, tenofovir, tobramycin and cyclosporin A [55][56][57], they also provide a unique opportunity to model AKI in a wide variety of additional etiologies (e.g., ischemia, hypoxia).…”

Section: Kidney On a Chipmentioning

confidence: 99%

Human Stem Cell and Organoid Models to Advance Acute Kidney Injury Diagnostics and Therapeutics

Pode‐Shakked

Devarajan

2022

IJMS

View full text Add to dashboard Cite

Acute kidney injury (AKI) is an increasingly common problem afflicting all ages, occurring in over 20% of non-critically ill hospitalized patients and >30% of children and >50% of adults in critical care units. AKI is associated with serious short-term and long-term consequences, and current therapeutic options are unsatisfactory. Large gaps remain in our understanding of human AKI pathobiology, which have hindered the discovery of novel diagnostics and therapeutics. Although animal models of AKI have been extensively studied, these differ significantly from human AKI in terms of molecular and cellular responses. In addition, animal models suffer from interspecies differences, high costs and ethical considerations. Static two-dimensional cell culture models of AKI also have limited utility since they have focused almost exclusively on hypoxic or cytotoxic injury to proximal tubules alone. An optimal AKI model would encompass several of the diverse specific cell types in the kidney that could be targets of injury. Second, it would resemble the human physiological milieu as closely as possible. Third, it would yield sensitive and measurable readouts that are directly applicable to the human condition. In this regard, the past two decades have seen a dramatic shift towards newer personalized human-based models to study human AKI. In this review, we provide recent developments using human stem cells, organoids, and in silico approaches to advance personalized AKI diagnostics and therapeutics.

show abstract

Human iPSC-derived renal organoids engineered to report oxidative stress can predict drug-induced toxicity

Cited by 18 publications

References 58 publications

Production of kidney organoids arranged around single ureteric bud trees, and containing endogenous blood vessels, solely from embryonic stem cells

Production of kidney organoids arranged around single ureteric bud trees, and containing endogenous blood vessels, solely from embryonic stem cells

Induced Pluripotent Stem Cell-Based Drug Screening by Use of Artificial Intelligence

Human Stem Cell and Organoid Models to Advance Acute Kidney Injury Diagnostics and Therapeutics

Contact Info

Product

Resources

About