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去细胞化异种肾支架的再细胞化:一种生成生物人工肾的体内方法。

Recellularization of Acellular Xeno Kidney Scaffold: An In Vivo Method to Generate Bioartificial Kidney.

机构信息

Department of Stem Cells & Regenerative Medicine, D Y Patil Education Society (Deemed to be University), Kolhapur, Maharashtra, India.

Department of Radiology, D Y Patil Medical College, D Y Patil Education Society (Deemed to be University), Kolhapur, Maharashtra, India.

出版信息

Adv Exp Med Biol. 2024;1450:77-92. doi: 10.1007/5584_2023_785.

DOI:10.1007/5584_2023_785
PMID:37610657
Abstract

A significant hurdle for kidney tissue engineering is reproducing the complex three-dimensional structure of the kidney. In our study, a stepwise approach of generating a reproducible Xeno kidney scaffold from a goat kidney is described, which can be implanted and recellularized by host cells. We have proposed a combination of sodium dodecyl sulfate and Triton-X-100-based protocol to generate a reproducible Xeno kidney scaffold, which was then analyzed by histology, DNA quantification, SEM, and renal angiography. Further, a small portion from the cortico-medullar region of the acellular scaffold was implanted in the rat's kidney subcapsular pocket for a period of 1 month, to check the recruitment of host cells into the scaffold. Post implantation, the extracellular matrix of the scaffold was well preserved and it did not induce any damage or inflammation in the native kidney. Implantation of the Xeno scaffold resulted in apparent early vascularization which helped in the recruitment of the host cells, which was characterized by histology, immunohistochemistry, and scanning electron microscopy. Implanted Xeno scaffold showed AQP-1, Nephrin, α-SMA, and VEGF expression in proximal tubules and renal glomerulus. Importantly, Ki-67 and WTAP-expressing cells were also observed near proximal tubules suggesting a high level of proliferation in the scaffold. Thus, showing the potential of Xeno kidney development that can be recellularized by the host cell to engineer into a functional kidney.

摘要

肾组织工程的一个重大障碍是复制肾脏的复杂三维结构。在我们的研究中,描述了一种从山羊肾脏生成可重复的异种肾脏支架的逐步方法,该支架可以被宿主细胞植入和再细胞化。我们提出了一种基于十二烷基硫酸钠和 Triton-X-100 的组合方案来生成可重复的异种肾脏支架,然后通过组织学、DNA 定量、SEM 和肾脏血管造影对其进行分析。此外,将脱细胞支架的皮质-髓质区域的一小部分植入大鼠肾脏的肾包膜下袋中 1 个月,以检查宿主细胞是否进入支架。植入后,支架的细胞外基质得到了很好的保存,并且没有在原生肾脏中引起任何损伤或炎症。异种支架的植入导致明显的早期血管化,有助于宿主细胞的募集,这一过程通过组织学、免疫组织化学和扫描电子显微镜得到了特征化。植入的异种支架在近端肾小管和肾小球中显示出 AQP-1、Nephrin、α-SMA 和 VEGF 的表达。重要的是,还在近端肾小管附近观察到 Ki-67 和 WTAP 表达的细胞,表明支架中有高水平的增殖。因此,表明异种肾脏发展的潜力,即可以通过宿主细胞再细胞化来构建成功能性肾脏。

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Recellularization of Acellular Xeno Kidney Scaffold: An In Vivo Method to Generate Bioartificial Kidney.去细胞化异种肾支架的再细胞化:一种生成生物人工肾的体内方法。
Adv Exp Med Biol. 2024;1450:77-92. doi: 10.1007/5584_2023_785.
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本文引用的文献

1
Regulation of Epithelial Cell Functions by the Osmolality and Hydrostatic Pressure Gradients: A Possible Role of the Tight Junction as a Sensor.渗透压和静水压力梯度对上皮细胞功能的调节:紧密连接作为传感器的可能作用。
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Novel Approach Toward the Generation of Tissue Engineered Heart Valve by Using Combination of Antioxidant and Detergent: A Potential Therapy in Cardiovascular Tissue Engineering.通过抗氧化剂与去污剂联合使用生成组织工程心脏瓣膜的新方法:心血管组织工程中的一种潜在疗法。
Tissue Eng Regen Med. 2017 Sep 18;14(6):755-762. doi: 10.1007/s13770-017-0070-1. eCollection 2017 Dec.
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Kidney regeneration: Where we are and future perspectives.
肾脏再生:我们所处的现状与未来展望。
World J Nephrol. 2014 Aug 6;3(3):24-30. doi: 10.5527/wjn.v3.i3.24.
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Chronic kidney disease: global dimension and perspectives.慢性肾脏病:全球维度与展望。
Lancet. 2013 Jul 20;382(9888):260-72. doi: 10.1016/S0140-6736(13)60687-X. Epub 2013 May 31.
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Endothelial microvascular networks affect gene-expression profiles and osteogenic potential of tissue-engineered constructs.内皮微血管网络影响组织工程构建体的基因表达谱和成骨潜力。
Stem Cell Res Ther. 2013 May 17;4(3):52. doi: 10.1186/scrt202.