Optimization of Renal Organoid and Organotypic Culture for Vascularization, Extended Development, and Improved Microscopy Imaging

Kaisto, Susanna; Saarela, Ulla; Dönges, Laura; Raykhel, Irina; Skovorodkin, Ilya; Vainio, Seppo

doi:10.3791/60995

Cited by 7 publications

(5 citation statements)

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“…To prevent this immune rejection, immunodeficient animals, such as BALB/c nude mice and NOD/SCID mice, are utilized. The most frequently used site of transplantation is under the renal capsule in non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice or athymic nude rats [ 16 , 17 , 18 ]. Van den Berg et al transplanted hiPSC-derived human kidney organoids into kidney capsules of NOD/SCID mice [ 12 ].…”

Section: Resultsmentioning

confidence: 99%

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Strategies for Improving Vascularization in Kidney Organoids: A Review of Current Trends

Konoe

Morizane

2023

Biology

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Kidney organoids possess the potential to revolutionize the treatment of renal diseases. However, their growth and maturation are impeded by insufficient growth of blood vessels. Through a PubMed search, we have identified 34 studies that attempted to address this challenge. Researchers are exploring various approaches including animal transplantation, organ-on-chips, and extracellular matrices (ECMs). The most prevalent method to promote the maturation and vascularization of organoids involves transplanting them into animals for in vivo culture, creating an optimal environment for organoid growth and the development of a chimeric vessel network between the host and organoids. Organ-on-chip technology permits the in vitro culture of organoids, enabling researchers to manipulate the microenvironment and investigate the key factors that influence organoid development. Lastly, ECMs have been discovered to aid the formation of blood vessels during organoid differentiation. ECMs from animal tissue have been particularly successful, although the underlying mechanisms require further research. Future research building upon these recent studies may enable the generation of functional kidney tissues for replacement therapies.

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Section: Resultsmentioning

confidence: 99%

“…Hence, some studies tested other sites for organoid transplantation ( Table 1 ). Kaisto et al have successfully vascularized kidney organoids by implanting organoids into the chorioallantoic membrane (CAM) of a chicken [ 18 , 23 ]. The CAM is a transparent and thin tissue that enables shorter operative time and real-time imaging.…”

Section: Resultsmentioning

confidence: 99%

Strategies for Improving Vascularization in Kidney Organoids: A Review of Current Trends

Konoe

Morizane

2023

Biology

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“…A major advantage relies in the CAM’s easy accessibility and low rejection rate to facilitate increasing the model’s complexity by engrafting 3D spheroids ( 118 , 119 ) or multicellular organoids. For instance, mature organoids derived from human-induced pluripotent stem cells (PSCs) rapidly connected to the vascular network of the chick embryo after transferring them on the CAM ( 120 ), and PSC–derived inner ear and kidney organoids demonstrated the model’s potential to optimize developmental maturity and functionality of organoids based on vascularization ( 121 , 122 ). Along similar lines, grafting of tumor organoids, also combined with immune cells and/or fibroblasts, reflecting tissue heterogeneity in cancer to a greater extent, can be employed ( 123 ).…”

Section: Discussionmentioning

confidence: 99%

In ovo model in cancer research and tumor immunology

2022

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Considering cancer not only as malignant cells on their own but as a complex disease in which tumor cells interact and communicate with their microenvironment has motivated the establishment of clinically relevant 3D models in past years. Technological advances gave rise to novel bioengineered models, improved organoid systems, and microfabrication approaches, increasing scientific importance in preclinical research. Notwithstanding, mammalian in vivo models remain closest to mimic the patient’s situation but are limited by cost, time, and ethical constraints. Herein, the in ovo model bridges the gap as an advanced model for basic and translational cancer research without the need for ethical approval. With the avian embryo being a naturally immunodeficient host, tumor cells and primary tissues can be engrafted on the vascularized chorioallantoic membrane (CAM) with high efficiencies regardless of species-specific restrictions. The extraembryonic membranes are connected to the embryo through a continuous circulatory system, readily accessible for manipulation or longitudinal monitoring of tumor growth, metastasis, angiogenesis, and matrix remodeling. However, its applicability in immunoncological research is largely underexplored. Dual engrafting of malignant and immune cells could provide a platform to study tumor-immune cell interactions in a complex, heterogenic and dynamic microenvironment with high reproducibility. With some caveats to keep in mind, versatile methods for in and ex ovo monitoring of cellular and molecular dynamics already established in ovo are applicable alike. In this view, the present review aims to emphasize and discuss opportunities and limitations of the chicken embryo model for pre-clinical research in cancer and cancer immunology.

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“…Another possibility would be the measurement of the weight or the volume of the cystic tissue to gain dose response curves, which has been utilized in a similar study for the assessment of drug concentrations for tumors on the CAM [ 31 ]. Furthermore, the successful grafting of kidney organoids that were derived from human pluripotent stem cells on the CAM illustrates the possibility of establishing functional blood circulation to the tissue [ 32 , 33 ]. However, it should also be evaluated how secondary effects of the treatment, such as a reduced blood supply to the human tissue due to damages of the CAM, contribute to the overall effectiveness of the substances.…”

Section: Discussionmentioning

confidence: 99%

A 3D In Vivo Model for Studying Human Renal Cystic Tissue and Mouse Kidney Slices

Bichlmayer

Mahl

Hesse

et al. 2022

Cells

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(1) Background: Autosomal dominant polycystic kidney disease (ADPKD) is a frequent monogenic disorder that leads to progressive renal cyst growth and renal failure. Strategies to inhibit cyst growth in non-human cyst models have often failed in clinical trials. There is a significant need for models that enable studies of human cyst growth and drug trials. (2) Methods: Renal tissue from ADPKD patients who received a nephrectomy as well as adult mouse kidney slices were cultured on a chorioallantoic membrane (CAM) for one week. The cyst volume was monitored by microscopic and CT-based applications. The weight and angiogenesis were quantified. Morphometric and histological analyses were performed after the removal of the tissues from the CAM. (3) Results: The mouse and human renal tissue mostly remained vital for about one week on the CAM. The growth of cystic tissue was evaluated using microscopic and CT-based volume measurements, which correlated with weight and an increase in angiogenesis, and was accompanied by cyst cell proliferation. (4) Conclusions: The CAM model might bridge the gap between animal studies and clinical trials of human cyst growth, and provide a drug-testing platform for the inhibition of cyst enlargement. Real-time analyses of mouse kidney tissue may provide insights into renal physiology and reduce the need for animal experiments.

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Optimization of Renal Organoid and Organotypic Culture for Vascularization, Extended Development, and Improved Microscopy Imaging

Cited by 7 publications

References 0 publications

Strategies for Improving Vascularization in Kidney Organoids: A Review of Current Trends

Strategies for Improving Vascularization in Kidney Organoids: A Review of Current Trends

In ovo model in cancer research and tumor immunology

A 3D In Vivo Model for Studying Human Renal Cystic Tissue and Mouse Kidney Slices

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