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

用于研究人类肾囊性组织和小鼠肾切片的 3D 体内模型

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作者:Eva-Marie Bichlmayer, Lina Mahl, Leo Hesse, Eric Pion, Victoria Haller, Andreas Moehwald, Christina Hackl, Jens M Werner, Hans J Schlitt, Siegfried Schwarz, Philipp Kainz, Christoph Brochhausen, Christian Groeger, Felix Steger, Oliver Kölbl, Christoph Daniel, Kerstin Amann, Andre Kraus, Björn Buchho

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)

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.

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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