Development of a two-stage model system to investigate the mineralization mechanisms involved in idiopathic stone formation: stage 2 in vivo studies of stone growth on biomimetic Randall's plaque.
Development of a two-stage model system to investigate the mineralization mechanisms involved in idiopathic stone formation: stage 2 in vivo studies of stone growth on biomimetic Randall's plaque.
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DOI：
10.1007/s00240-018-1079-1
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发表时间：
2019-08
期刊：
影响因子：
3.1
通讯作者：
Khan SR
中科院分区：
文献类型：
--
作者：
O'Kell AL;Lovett AC;Canales BK;Gower LB;Khan SR
特发性结石形成者通常形成草酸钙(CaOx)结石，附着在肾组织中的磷酸钙(CaP)沉积物上，称为兰德尔斑块(RP)。斑块可能起源于肾小管基底膜，并扩散到间质区域，在那里胶原纤维和囊泡变成矿化；如果上皮被破坏，暴露在尿液中的RP就会被CaOx覆盖。我们建立了CaOx复合结石的两阶段模型系统，包括第一阶段的CaOx矿化斑块和第二阶段的CaOx过度生长成结石。在本系列的第一篇论文中(阶段1)，骨桥蛋白(和聚天冬氨酸)被发现能诱导猪肾组织的非经典矿化，产生类似RP的特征。在这里介绍的第二阶段研究中，第一阶段的仿生RP被植入到大鼠的膀胱中。用乙二醇法诱导高草酸尿症，并与对照组(水)进行比较。4周后处死大鼠，用电子显微镜和X射线显微分析对种植体进行分析。基于仿生斑块中存在的大分子在晶相和形貌上的差异，表明仿生斑块具有调节结晶反应的能力。正如预期的那样，植入物上的矿物质过度生长从CaOx(水)转变为CaOx(高草酸)。CaOx晶体聚集并与仿生快速成型的有机物质混合在一起，同时在“石头”表面附近有一些无定形和球状的CaOx，这些CaOx似乎变得致密和有组织地向外围移动。与其他已发表的模型相比，该系统成功地诱导出了更类似于人类特发性肾结石的“结石”。
Idiopathic stone formers often form calcium oxalate (CaOx) stones that are 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 and spread into the interstitial regions where collagen fibrils and vesicles become mineralized; if the epithelium is breached, the RP becomes overgrown with CaOx upon exposure to urine. We have developed 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. In our first paper in this series (Stage 1), osteopontin (and polyaspartate) were found to induce a non-classical mineralization of porcine kidney tissues, producing features that resemble RP. For the Stage 2 studies presented here, biomimetic RPs from Stage 1 were implanted into the bladders of rats. Hyperoxaluria was induced with ethylene glycol for comparison to controls (water). After 4 weeks, rats were sacrificed and the implants analyzed using electron microscopy and x-ray microanalyses. Differences in crystal phase and morphologies based upon the macromolecules present in the biomimetic plaques suggest that the plaques have the capacity to modulate the crystallization reactions. As expected, mineral overgrowths on the implants switched from CaP (water) to CaOx (hyperoxaluric). The CaOx crystals were aggregated and mixed with organic material from the biomimetic RP, along with some amorphous and spherulitic CaOx near the “stone” surfaces, which seemed to become compact and organized towards the periphery. This system was successful at inducing “stones” more similar to human idiopathic kidney stones than other published models.
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影响因子：
--
作者：
Khan SR
通讯作者：
Khan SR
影响因子：
3.1
作者：
Evan AP;Worcester EM;Coe FL;Williams J Jr;Lingeman JE
通讯作者：
Lingeman JE
影响因子：
6.1
作者：
Parks, Joan H.;Coe, Fredric L.;Worcester, Elaine M.
通讯作者：
Worcester, Elaine M.
DOI：
10.1111/j.1464-410x.1989.tb05276.x
发表时间：
1989-11-01
期刊：
BRITISH JOURNAL OF UROLOGY
影响因子：
--
作者：
HALLSON, PC;ROSE, GA
通讯作者：
ROSE, GA
DOI：
10.1152/ajprenal.00620.2007
发表时间：
2008-05-01
影响因子：
4.2
作者：
Khan, Saeed R.;Glenton, Patricia A.
通讯作者：
Glenton, Patricia A.