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Development of a two-stage in vitro model system to investigate the mineralization mechanisms involved in idiopathic stone formation: stage 1—biomimetic Randall’s plaque using decellularized porcine kidneys

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Abstract

Idiopathic calcium oxalate (CaOx) stone formers form stones that are commonly attached to calcium phosphate (CaP) deposits in the renal tissue, known as Randall’s plaques (RP). Plaques are suggested to originate in the renal tubular basement membrane, where they exhibit a morphology of concentrically laminated apatitic spherules, while in the interstitial regions, the collagen fibrils and vesicles become mineralized. We hypothesize that these minerals might form by non-classical crystallization mechanisms, such as via amorphous precursors, some of which might originate from a polymer-induced liquid-precursor (PILP) process. Thus, our goal is to identify mineralogical ‘signatures’ of various stone formation mechanisms. To do this for idiopathic CaOx stones, we are developing a two-stage model system of CaP–CaOx composite stones, consisting of stage (1) CaP mineralized plaque, followed by stage (2) CaOx overgrowth into a stone. For the studies presented here, decellularized porcine kidneys were mineralized with CaP using polyaspartic acid or the protein osteopontin (OPN) to induce the PILP process and create biomimetic RP. Analysis of the PILP-mineralized tissues shows features that resemble the native plaques, including mineral spherules and collagen with intrafibrillar mineral. In contrast, the classical crystallization produced large apatitic spherulites, which is a very different morphology, but one which is also found in some stones. An alternative hypothesis regarding Randall’s plaque, and if or when it becomes pathological, is discussed.

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Acknowledgements

Research reported in this publication was supported by the National Institute of Diabetes And Digestive And Kidney Diseases of the National Institutes of Health under Award Number R01DK092311. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. We thank Drs. Brad Willenberg, Edward Ross (College of Medicine, University of Central Florida), and Christopher Batich (Department of Materials Science and Engineering, University of Florida) for providing the decellularized porcine kidney tissues. We would also like to thank Drs. Sharon Matthews and Jill Verlander for their training and expertise in tissue sample preparation, microtomy, and microscopy done at the College of Medicine Electron Microscopy Core Facility at the University of Florida.

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  1. Department of Materials Science and Engineering, University of Florida, Gainesville, FL, 32611, USA

    Archana C. Lovett & Laurie B. Gower

  2. Department of Pathology, College of Medicine, University of Florida, Gainesville, FL, 32610, USA

    Saeed R. Khan

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Lovett, A.C., Khan, S.R. & Gower, L.B. Development of a two-stage in vitro model system to investigate the mineralization mechanisms involved in idiopathic stone formation: stage 1—biomimetic Randall’s plaque using decellularized porcine kidneys. Urolithiasis 47, 321–334 (2019). https://doi.org/10.1007/s00240-018-1060-z

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