Magnetic resonance imaging-based risk factors of hepatocellular carcinoma after direct-acting antiviral therapy: A multicenter observational study.

AIM: To determine risk factors associated with hepatocellular carcinoma (HCC) development following direct-acting antiviral (DAA) therapy. METHODS: We enrolled patients with chronic hepatitis C who underwent direct-acting antiviral therapy and achieved sustained virologic response at 12 weeks between 2012 and 2018. Subsequently, patients were followed up. The primary endpoint was the development of HCC or the date of the last follow up when the absence of HCC was confirmed. Uni- and multivariate Cox proportional hazards models were used to identify factors contributing to HCC development, including gadoxetic acid-enhanced magnetic resonance imaging findings. The cumulative incidence rates of HCC development were calculated using the Kaplan-Meier method, and differences between groups were assessed using the log-rank test. RESULTS: The final study cohort comprised 482 patients (median age 70.5 years; 242 men). The median follow-up period was 36.8 months. Among 482 patients, 96 developed HCC (19.9%). The 1-, 3-, and 5-year cumulative rates of HCC development were 4.9%, 18.6%, and 30.5%, respectively. Multivariate analysis revealed that age, male sex, history of HCC, and hepatobiliary phase hypointense nodules without arterial phase hyperenhancement were independent risk factors significantly associated with HCC development (p < 0.001-0.04). The highest risk group included patients with both a history of HCC and the presence of hepatobiliary phase hypointense nodules without arterial phase hyperenhancement (the 1- and 3-year cumulative HCC development rates were 14.2% and 62.2%, respectively). CONCLUSION: History of HCC and presence of hepatobiliary phase hypointense nodules without arterial phase hyperenhancement were strong risk factors for HCC development following direct-acting antiviral therapy.

An organic transistor matrix for multipoint intracellular action potential recording.

Electrode arrays are widely used for multipoint recording of electrophysiological activities, and organic electronics have been utilized to achieve both high performance and biocompatibility. However, extracellular electrode arrays record the field potential instead of the membrane potential itself, resulting in the loss of information and signal amplitude. Although much effort has been dedicated to developing intracellular access methods, their three-dimensional structures and advanced protocols prohibited implementation with organic electronics. Here, we show an organic electrochemical transistor (OECT) matrix for the intracellular action potential recording. The driving voltage of sensor matrix simultaneously causes electroporation so that intracellular action potentials are recorded with simple equipment. The amplitude of the recorded peaks was larger than that of an extracellular field potential recording, and it was further enhanced by tuning the driving voltage and geometry of OECTs. The capability of miniaturization and multiplexed recording was demonstrated through a 4 × 4 action potential mapping using a matrix of 5- × 5-µm2 OECTs. Those features are realized using a mild fabrication process and a simple circuit without limiting the potential applications of functional organic electronics.

Muscle cell proliferation using water-soluble extract from nitrogen-fixing cyanobacteria Anabaena sp. PCC 7120 for sustainable cultured meat production.

Muscle cell cultivation, specifically the culture of artificial meat from livestock-derived cells in serum-free media is an emerging technology and has attracted much attention. However, till now, the high cost of production and environmental load have been significant deterrents. This study aims to provide an alternate growth-promoting substance that is free from animal derivatives and lowers nitrogen pollution. We have extracted water-soluble compounds from the filamentous nitrogen-fixing cyanobacteria Anabaena sp. PCC 7120 by the ultrasonication method. The heat-inactivated and molecular weight separation experiments were conducted to identify the bioactive compound present in the extract. Finally, the compounds soluble in water (CW) containing the water-soluble pigment protein, phycocyanin as a bioactive compound, was added as a growth supplement to cultivate muscle cells such as C2C12 muscle cells and quail muscle clone 7 (QM7) cells to analyze the effectiveness of the extract. The results indicated that CW had a positive role in muscle cell proliferation. A three-dimensional (3-D) cell-dense structure was fabricated by culturing QM7 cells using the extract. Furthermore, the nitrogen-fixing cyanobacterial extract has vast potential for cultured meat production without animal sera in the near future.

Circular cell culture for sustainable food production using recombinant lactate-assimilating cyanobacteria that supplies pyruvate and amino acids.

Recently, we reported a circular cell culture (CCC) system using microalgae and animal muscle cells for sustainable culture food production. However, lactate accumulation excreted by animal cells in the system characterized by medium reuse was a huge problem. To solve the problem, as an advanced CCC, we used a lactate-assimilating cyanobacterium Synechococcus sp. PCC 7002, using gene-recombination technology that synthesises pyruvate from lactate. We found that the cyanobacteria and animal cells mutually exchanged substances via their waste media: (i) cyanobacteria used lactate and ammonia excreted by animal muscle cells, and (ii) the animal cells used pyruvate and some amino acids excreted by the cyanobacteria. Because of this, animal muscle C2C12 cells were amplified efficiently without animal serum in cyanobacterial culture waste medium in two cycles (first cycle: 3.6-fold; second cycle: 3.9-fold/three days-cultivation) using the same reuse medium. We believe that this advanced CCC system will solve the problem of lactate accumulation in cell culture and lead to efficient cultured food production.

Impact of craniotomy area on improvement of cerebral blood flow in combined revascularization surgery for moyamoya disease.

OBJECTIVE: To investigate factors associated with improvements in cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) after combined revascularization surgery for moyamoya disease, with special attention to the size of craniotomy. METHODS: We retrospectively analyzed 35 hemispheres in 27 patients with adult and older pediatric moyamoya disease. CBF and CVR were measured separately in the MCA and ACA territories from acetazolamide-challenged single-photon emission computed tomography before and after 6 months postoperatively, and associations with various factors were analyzed. RESULTS: Postoperative CBF improved in patients with lower preoperative blood flow in both ACA and MCA territories. Postoperative CVR improved in 32 of 35 patients (91.4%) in the MCA territory and in 30 of 35 patients (85.7%) in the ACA territory, with more prominent improvement in the MCA territory than in the ACA territory (MCA territory 29.7% vs ACA territory 21.1%, p = 0.015). Craniotomy area did not correlate with postoperative CBF and only MCA territory was associated with good (≥30%) CVR improvement (odds ratio 9.33, 95% confidence interval 1.91-45.6, p = 0.003). CONCLUSIONS: Postoperative CBF improved in adult and older pediatric cases, reflecting preoperative CBF. Postoperative CVR improved in most cases, although the degree of improvement was more prominent in the MCA territory than in the ACA territory, suggesting a contribution of the temporal muscle. Large craniotomy area was not associated with improved blood flow in the ACA territory and should be applied prudently.

Perfusable vascular tree like construction in 3D cell-dense tissues using artificial vascular bed.

Perfusable vascular structures in cell-dense tissues are essential for fabricating functional three-dimensional (3D) tissues in vitro. However, it is challenging to introduce functional vascular networks observable as vascular tree, finely spaced at intervals of tens of micrometers as in living tissues, into a 3D cell-dense tissue. Herein, we propose a method for introducing numerous vascular networks that can be perfused with blood into 3D tissues constructed by cell sheet engineering. We devise an artificial vascular bed using a hydrogel that is barely deformed by cells, enabling perfusion of the culture medium directly beneath the cell sheets. Triple-layered cell sheets with an endothelial cell network prepared by fibroblast co-culture are transplanted onto the vascular bed and subjected to perfusion culture. We demonstrate that numerous vascular networks are formed with luminal structures in the cell sheets and can be perfused with India ink or blood after a five-day perfusion culture. Histological analysis also demonstrates that perfusable vascular structures are constructed at least 100 µm intervals uniformly and densely within the tissues. The results suggest that our perfusion culture method enhances vascularization within the 3D cell-dense tissues and enables the introduction of functional vasculature macroscopically observable as vascular tree in vitro. In conclusion, this technology can be used to fabricate functional tissues and organs for regenerative therapies and in vitro experimental models.

A circular cell culture system using microalgae and mammalian myoblasts for the production of sustainable cultured meat.

For sustainable production of cultured meat, we propose a novel circular cell culture (CCC) system in which microalgae are used as nutrient supply for the mammalian cell culture and as a waste-medium recycler. Chlorococcum littorale, RL34 hepatocytes, and C2C12 myoblasts were used as cell sources for microalgae, growth factor-producing cells, and muscle cells, respectively. In the first cycle, C2C12 cells were amplified 4.0-fold after 48 h of culture in an RL34 cell-conditioned medium. In the second cycle, C2C12 cells were cultured in the C. littorale culture waste medium to which the C. littorale-derived nutrients were added. The proliferation rates of C. littorale and C2C12 and the nutrient extraction efficiency from C. littorale were the same in the first and second cycles. Therefore, this CCC system, which works without additional grain-derived nutrients and animal sera, will help drastically reduce environmental load, resource/energy consumption, and costs in future cultured meat production.

Functional Evaluation of Human Bioengineered Cardiac Tissue Using iPS Cells Derived from a Patient with Lamin Variant Dilated Cardiomyopathy.

Dilated cardiomyopathy (DCM) is caused by various gene variants and characterized by systolic dysfunction. Lamin variants have been reported to have a poor prognosis. Medical and device therapies are not sufficient to improve the prognosis of DCM with the lamin variants. Recently, induced pluripotent stem (iPS) cells have been used for research on genetic disorders. However, few studies have evaluated the contractile function of cardiac tissue with lamin variants. The aim of this study was to elucidate the function of cardiac cell sheet tissue derived from patients with lamin variant DCM. iPS cells were generated from a patient with lamin A/C (LMNA) -mutant DCM (LMNA p.R225X mutation). After cardiac differentiation and purification, cardiac cell sheets that were fabricated through cultivation on a temperature-responsive culture dish were transferred to the surface of the fibrin gel, and the contractile force was measured. The contractile force and maximum contraction velocity, but not the maximum relaxation velocity, were significantly decreased in cardiac cell sheet tissue with the lamin variant. A qRT-PCR analysis revealed that mRNA expression of some contractile proteins, cardiac transcription factors, Ca2+-handling genes, and ion channels were downregulated in cardiac tissue with the lamin variant.Human iPS-derived bioengineered cardiac tissue with the LMNA p.R225X mutation has the functional properties of systolic dysfunction and may be a promising tissue model for understanding the underlying mechanisms of DCM.

[Refractory thrombotic thrombocytopenic purpura complicated with multiple cerebral infarction].

Neuropsychiatric symptoms comprise one of the five classic symptoms of autoimmune thrombotic thrombocytopenic purpura (aTTP). Although aTTP is typically transient, it is sometimes complicated by cerebral infarction with residual disability. This report presents the case of an 87-year-old man previously admitted to a different hospital with fever and transient consciousness loss. After receiving platelet transfusion with diagnosis of Evans syndrome, he was transferred to our hospital with worsening consciousness disturbance. He was subsequently diagnosed with aTTP with a PLASMIC score of 6 points, ADAMTS13 activity of less than 0.5%, and its inhibitor of 7.4 BU/ml. Platelet count and consciousness were rapidly improved with plasmapheresis and steroids, but motor aphasia emerged. MRI showed multiple cerebral infarctions, including a large infarction in the left frontal lobe. Thus, unfractionated heparin was administered. When his platelet count dropped once again on the 20th day, rituximab was added. The treatment eventually proved to be successful, and his aTTP remained in remission one year after the onset. Treatment for cerebral infarctions was switched to DOAC, and rehabilitation was continued. However, his ADL has not yet recovered. Advances in aTTP treatment have cured many similar cases. Thus, rituximab is now considered a treatment option for refractory cases. However, ischemic organ damage in acute phase and sequelae are observed. Therefore, early diagnosis and novel therapy are required.

Development and Preclinical Study of Free Radical Imaging Using Field-Cycling Dynamic Nuclear Polarization MRI.

Free radicals, such as metabolic intermediates, reactive oxygen species, and metal enzymes, are key substances in organisms, although they can also cause various oxidative diseases. Thus, in vivo free radical imaging should be considered as the ultimate form of metabolic imaging. Unfortunately, electron spin resonance (ESR) imaging has inherent disadvantages, such as free radicals with large linewidths generating blurred images and the presence of two or more free radicals resulting in a complicated imaging procedure. Dynamic nuclear polarization-magnetic resonance imaging (DNP-MRI) is a noninvasive imaging method to visualize in vivo free radicals, theoretically, with the same resolution as the MRI anatomical resolution, and fixed low-field DNP-MRI provides unique information on oxidative diseases and cancer. However, the large gyromagnetic ratio of the electron spin, which is 660-fold greater than that of a proton, requires field cycling, wherein the external magnetic field should be varied during DNP-MRI observations. This causes difficulties in developing a DNP-MRI system for clinical purposes. We developed a novel field-cycling DNP-MRI system for a preclinical study. In the said system, the magnetic field is switched by rotationally moving two magnets, with a magnetic flux density of 0.3 T for MRI and 5 mT for ESR. The image quality was examined using various pulse sequences and ESR irradiation using nitroxyl radical as the phantom, and the optimum conditions were established. Using the system, we performed a preclinical study involving free radical imaging by placing the free radicals under the palm of a human hand.

Simulated microgravity accelerates aging of human skeletal muscle myoblasts at the single cell level.

Earth's gravity is essential for maintaining skeletal muscle mass and function in the body. The role of gravity in the myogenic mechanism has been studied with animal experiments in the International Space Station. Recently, gravity-control devices allow to study the effects of gravity on cultured cells on the ground. This study demonstrated that simulated microgravity accelerated aging of human skeletal muscle myoblasts in an in-vitro culture. The microgravity culture induced a significant decrease in cell proliferation and an enlargement of the cytoskeleton and nucleus of cells. Similar changes are often observed in aged myoblasts following several passages. In fact, by the microgravity culture the expression of senescence associated ß-Gal was significantly enhanced, and some muscle-specific proteins decreased in the enlarged cells. Importantly, these microgravity effects remained with the cells even after a return to normal gravity conditions. Consequently, the microgravity-affected myoblasts demonstrated a reduced capability of differentiation into myotubes. In the body, it is difficult to interpret the disability of microgravity-affected myoblasts, since muscle regeneration is linked to the supply of new myogenic cells. Therefore, our in-vitro cell culture study will be advantageous to better understand the role of each type of myogenic cell in human muscle without gravitational stress at the single cell level.

Kidney organoids: Research in developmental biology and emerging applications.

Kidney organoids generated from human pluripotent stem cells (hPSCs) have drastically changed the field of stem cell research on human kidneys within a few years. They are self-organizing multicellular structures that contain nephron components such as glomeruli and renal tubules in most cases, but hPSC-derived ureteric buds, the progenitors of collecting ducts and ureters, can also form three-dimensional organoids. Today's challenges facing human kidney organoids are further maturation and anatomical integrity in order to achieve a complete model of the developing kidneys and ultimately a complete adult organ. Since chronic kidney disease (CKD) and impaired kidney function are an increasing burden on public health worldwide, there is an urgent need to develop effective treatments for various renal conditions. In this regard, hPSC-derived kidney organoids may impact medicine by providing new translational approaches. The unique ability of kidney organoids derived from disease-specific hPSCs to reproduce human diseases caused by genetic alterations may help provide the next generation of kidney disease models. Recent advances in the field of kidney organoid research have been generally accompanied by progress in developmental biology and other technological breakthroughs. In this review, we consider the current trends in kidney organoid technology, especially focusing on the relationship to the study of human kidney development, and discuss the remaining hurdles and prospects in regenerating human kidney structures beyond organoids.

Microalgal culture in animal cell waste medium for sustainable 'cultured food' production.

'Cultured food' has tremendous potential as a sustainable meat alternative. Increased cultured food production is increasing the amount of waste medium from cell culture. Nitrogen- and phosphorus-containing compounds in waste medium can cause eutrophication of water bodies. Currently, microalgae are used in energy production, environmental protection, agriculture and pharmaceutical and health food industries. Here, we used the microalgae, Chlorococcum littorale and Chlorella vulgaris and the waste medium of C2C12 cells for a case study. We found that 80% and 26% of ammonia and 16% and 15% of phosphorus in the waste medium were consumed by C. littorale and C. vulgaris, respectively. In addition, C. littorale and C. vulgaris proliferated 3.2 folds and 1.6 folds, respectively, after seven days in the waste medium that was enhanced by adjusting medium salt concentration. This report demonstrates the potential of sustainability for solving the issue of waste medium production during the production of cultured food.

Literature review of allograft adenovirus nephritis and a case presenting as mass lesions in a transplanted kidney without symptoms of urinary tract infection or acute kidney injury.

Adenovirus (AdV) infection is a common complication in bone marrow/hematopoietic stem cell transplant and solid organ transplant recipients. AdV infection usually presents as hemorrhagic cystitis, but sometimes it can progress to acute kidney injury showing AdV nephritis (AdVN). We present the case of a 52-year-old Japanese female who had received a living kidney transplantation (KT) from her husband. At 21 months post-KT, the patient presented with a fever, but no renal dysfunction and no abnormal urine findings. A contrast-enhanced computed tomography (CT) scan revealed a few mass lesions with hypoperfusion in the transplanted kidney. An enhanced CT-guided biopsy targeting one of these lesions revealed a necrotizing tubulointerstitial nephritis suggesting AdVN. The polymerase chain reaction tests for ADV were negative in a urine sample but positive in the sera and the frozen kidney biopsy samples. AdVN can manifest as an unusual pattern of acute lobar nephritis/acute focal bacterial nephritis-like localization without symptoms of acute kidney injury or urinary tract infection. Enhanced CT can provide clues for clinical diagnosis.

Continuous measurement of surface electrical potentials from transplanted cardiomyocyte tissue derived from human-induced pluripotent stem cells under physiological conditions in vivo.

Recording the electrical potentials of bioengineered cardiac tissue after transplantation would help to monitor the maturation of the tissue and detect adverse events such as arrhythmia. However, a few studies have reported the measurement of myocardial tissue potentials in vivo under physiological conditions. In this study, human-induced pluripotent stem cell-derived cardiomyocyte (hiPSCM) sheets were stacked and ectopically transplanted into the subcutaneous tissue of rats for culture in vivo. Three months after transplantation, a flexible nanomesh sensor was implanted onto the hiPSCM tissue to record its surface electrical potentials under physiological conditions, i.e., without the need for anesthetic agents that might adversely affect cardiomyocyte function. The nanomesh sensor was able to record electrical potentials in non-sedated, ambulating animals for up to 48 h. When compared with recordings made with conventional needle electrodes in anesthetized animals, the waveforms obtained with the nanomesh sensor showed less dispersion of waveform interval and waveform duration. However, waveform amplitude tended to show greater dispersion for the nanomesh sensor than for the needle electrodes, possibly due to motion artifacts produced by movements of the animal or local tissue changes in response to surgical implantation of the sensor. The implantable nanomesh sensor utilized in this study potentially could be used for long-term monitoring of bioengineered myocardial tissue in vivo under physiological conditions.

Three-dimensional tissue fabrication system by co-culture of microalgae and animal cells for production of thicker and healthy cultured food.

OBJECTIVES: "Cultured food" is focused worldwide as "the third stage in meat production system" after hunting and livestock farming, and a sustainable food production system. In this study, we attempted to fabricate a three-dimensional (3-D) tissue by co-cultivation of animal cells with photosynthetic autotrophic microalgae so as to produce thicker and healthy cultured foods. RESULTS: Metabolism and damage of co-cultured tissues fabricated by microalgae, Chlorella vulgaris (C. vulgaris), and C2C12 cells were compared to monoculture tissues fabricated by C2C12 animal cells alone. Although the metabolism of monoculture tissue showed anaerobic respiration (ratio of lactate production to glucose consumption, LG ratio: 2.01 ± 0.15), that of the co-culture tissue partially changed to efficient aerobic respiration (LG ratio: 1.58 ± 0.14). In addition, the amount of ammonia in the culture media decreased markedly by co-cultivation. The release of lactate dehydrogenase from the thicker tissue was one-seventh in the co-cultivation, showing improved tissue damage. The co-cultivation with microalgae improved the culture condition of thicker tissues, resulting in the fabrication/maintenance of 200-400 µm-thickness tissues. The co-cultured tissue fabricated by microalgae and animal cells was not only rich in nutrients but also enabled thicker tissue fabrication without tissue damage as compared to tissue fabricated by animal cells alone. CONCLUSIONS: This tissue fabrication system by co-culture of microalgae and animal cells will be a valuable tool for the production of thicker and healthy cultured food.

Fundamental Technologies and Recent Advances of Cell-Sheet-Based Tissue Engineering.

Tissue engineering has attracted significant attention since the 1980s, and the applications of tissue engineering have been expanding. To produce a cell-dense tissue, cell sheet technology has been studied as a promising strategy. Fundamental techniques involving tissue engineering are mainly introduced in this review. First, the technologies to fabricate a cell sheet were reviewed. Although temperature-responsive polymer-based technique was a trigger to establish and spread cell sheet technology, other methodologies for cell sheet fabrication have also been reported. Second, the methods to improve the function of the cell sheet were investigated. Adding electrical and mechanical stimulation on muscle-type cells, building 3D structures, and co-culturing with other cell species can be possible strategies for imitating the physiological situation under in vitro conditions, resulting in improved functions. Finally, culture methods to promote vasculogenesis in the layered cell sheets were introduced with in vivo, ex vivo, and in vitro bioreactors. We believe the present review that shows and compares the fundamental technologies and recent advances for cell-sheet-based tissue engineering should promote further development of tissue engineering. The development of cell sheet technology should promote many bioengineering applications.

Acute Endovascular Revascularization for Patients with Common Carotid Artery Occlusion Apparent on Cervical Magnetic Resonance Angiography.

OBJECTIVES: In the endovascular treatment of acute cerebral large-vessel occlusion, cervical magnetic resonance angiography (MRA) is a useful modality for assessing the access route. However, we sometimes encounter cases in which not only the internal carotid artery (ICA), but also the common carotid artery (CCA) is poorly visualized, leading to hesitation over which devices and techniques to choose for revascularization. We retrospectively evaluated such cases, focusing on image findings and treatment results. MATERIALS AND METHODS: Data from 96 patients who underwent acute endovascular revascularization from January 2016 to December 2019 were analyzed. We extracted patients with poor CCA visualization on cervical MRA from 35 cases with ICA occlusion, and examined angiographic findings, treatment methods, and outcomes. RESULTS: Poor visualization of the CCA in cervical MRA was observed in 8 cases. All cases displayed atrial fibrillation or sick sinus syndrome. Angiographic findings showed true CCA occlusion in 2 patients and ICA occlusion in 6 patients. Reasons for the inability to visualize the CCA on cervical MRA were speculated to be stenosis of the external carotid artery (ECA), presence of embolism in the ECA, or severe heart failure. In cases of true CCA occlusion, thrombus was aspirated using the balloon guide catheter and good recanalization was obtained. Seven of 8 patients displayed favorable recanalization, with good prognosis after 90 days in 5 patients. CONCLUSIONS: Poor CCA visualization on cervical MRA does not necessarily represent true CCA occlusion. Aspiration of thrombus from a balloon guide catheter is effective for true CCA occlusion.

Perfusable System Using Porous Collagen Gel Scaffold Actively Provides Fresh Culture Media to a Cultured 3D Tissue.

Culturing three-dimensional (3D) tissues with an appropriate microenvironment is a critical and fundamental technology in broad areas of cutting-edge bioengineering research. In addition, many technologies have engineered tissue functions. However, an effective system for transporting nutrients, waste, or oxygen to affect the functions of cell tissues has not been reported. In this study, we introduce a novel system that employs diffusion and convection to enhance transportation. To demonstrate the concept of the proposed system, three layers of normal human dermal fibroblast cell sheets are used as a model tissue, which is cultured on a general dish or porous collagen scaffold with perfusable channels for three days with and without the perfusion of culture media in the scaffold. The results show that the viability of the cell tissue was improved by the developed system. Furthermore, glucose consumption, lactate production, and oxygen transport to the tissues were increased, which might improve the viability of tissues. However, mechanical stress in the proposed system did not cause damage or unintentional functional changes in the cultured tissue. We believe that the introduced culturing system potentially suggests a novel standard for 3D cell cultures.

A novel ADPKD model using kidney organoids derived from disease-specific human iPSCs.

Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary disorder which manifests progressive renal cyst formation and leads to end-stage kidney disease. Around 85% of cases are caused by PKD1 heterozygous mutations, exhibiting relatively poorer renal outcomes than those with mutations in other causative gene PKD2. Although many disease models have been proposed for ADPKD, the pre-symptomatic pathology of the human disease remains unknown. To unveil the mechanisms of early cytogenesis, robust and genetically relevant human models are needed. Here, we report a novel ADPKD model using kidney organoids derived from disease-specific human induced pluripotent stem cells (hiPSCs). Importantly, we found that kidney organoids differentiated from gene-edited heterozygous PKD1-mutant as well as ADPKD patient-derived hiPSCs can reproduce renal cysts. Further, we demonstrated the possibility of ADPKD kidney organoids serving as drug screening platforms. This newly developed model will contribute to identifying novel therapeutic targets, extending the field of ADPKD research.