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本文引用的文献

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Generation of Human Fatty Livers Using Custom-Engineered Induced Pluripotent Stem Cells with Modifiable SIRT1 Metabolism.使用可修饰的 SIRT1 代谢物的定制工程诱导多能干细胞生成人源脂肪肝。
Cell Metab. 2019 Aug 6;30(2):385-401.e9. doi: 10.1016/j.cmet.2019.06.017.
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Bio-scaffolds in organ-regeneration: Clinical potential and current challenges.生物支架在器官再生中的应用:临床潜力与当前挑战。
Curr Res Transl Med. 2017 Sep;65(3):103-113. doi: 10.1016/j.retram.2017.08.002. Epub 2017 Sep 12.
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A novel three-dimensional culture system maintaining the physiological extracellular matrix of fibrotic model livers accelerates progression of hepatocellular carcinoma cells.一种新型三维培养系统,可维持肝纤维化模型的生理细胞外基质,加速肝癌细胞的进展。
Sci Rep. 2017 Aug 29;7(1):9827. doi: 10.1038/s41598-017-09391-y.
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Evolution of graft morphology and function after recellularization of decellularized rat livers.去细胞化大鼠肝脏再细胞化后移植物形态和功能的演变。
J Tissue Eng Regen Med. 2018 Feb;12(2):e807-e816. doi: 10.1002/term.2383. Epub 2017 Jun 26.
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Comparative biology of decellularized lung matrix: Implications of species mismatch in regenerative medicine.脱细胞肺基质的比较生物学:再生医学中物种不匹配的影响。
Biomaterials. 2016 Sep;102:220-30. doi: 10.1016/j.biomaterials.2016.06.025. Epub 2016 Jun 16.
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Biocompatibility evaluation of tissue-engineered decellularized scaffolds for biomedical application.用于生物医学应用的组织工程去细胞支架的生物相容性评估。
Mater Sci Eng C Mater Biol Appl. 2016 Oct 1;67:766-778. doi: 10.1016/j.msec.2016.05.068. Epub 2016 May 16.
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Isolation and co-culture of rat parenchymal and non-parenchymal liver cells to evaluate cellular interactions and response.大鼠肝实质细胞和非实质细胞的分离与共培养,以评估细胞间相互作用和反应。
Sci Rep. 2016 May 4;6:25329. doi: 10.1038/srep25329.
8
Development of Synthetic and Natural Materials for Tissue Engineering Applications Using Adipose Stem Cells.利用脂肪干细胞开发用于组织工程应用的合成材料和天然材料
Stem Cells Int. 2016;2016:5786257. doi: 10.1155/2016/5786257. Epub 2016 Feb 10.
9
Decellularization and cell seeding of whole liver biologic scaffolds composed of extracellular matrix.由细胞外基质组成的全肝生物支架的去细胞化和细胞接种
J Clin Exp Hepatol. 2015 Mar;5(1):69-80. doi: 10.1016/j.jceh.2014.03.043. Epub 2014 Mar 28.
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Recellularization of rat liver scaffolds by human liver stem cells.人肝干细胞对大鼠肝脏支架的再细胞化
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生物工程化器官的构建:使用生物去细胞化大鼠肝支架和肝细胞。

Development of Bioengineered Organ Using Biological Acellular Rat Liver Scaffold and Hepatocytes.

机构信息

Stem Cell Unit, Global Medical Education & Research Foundation , Hyderabad, India.

Transplant Immunology & Stem Cell Unit, Gleneagles Global Hospitals , Hyderabad, India.

出版信息

Organogenesis. 2020 Apr 2;16(2):61-72. doi: 10.1080/15476278.2020.1742534. Epub 2020 May 3.

DOI:10.1080/15476278.2020.1742534
PMID:32362216
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7531620/
Abstract

The increasing demand for organs for transplantation necessitates the development of substitutes to meet the structural and physiological functions. Tissue decellularization and recellularization aids in retaining the three-dimensional integrity, biochemical composition, tissue ultra-structure, and mechanical behavior, which makes them functionally suitable for organ transplantation. Herein, we attempted to rebuild functional liver grafts in small animal model (Wistar rat) with a potential of translation. A soft approach was adopted using 0.1% SDS (Sodium Dodecyl Sulfate) for decellularization and primary hepatocytes were used as a potential cell source for recellularization. The decellularization process was evaluated and confirmed using histology, DNA content, ultra-structure analysis. The resultant scaffold was re-seeded with the rat hepatocytes and their biocompatibility was assessed by its metabolic functions and gene expression. The structural components of the Extracellular matrix (ECM) (Laminins, Collagen type I, Reticulins) were conserved and the liver cell-specific proteins like CK-18, alpha-fetoprotein, albumin were expressed in the recellularized scaffold. The functionality and metabolic activity of the repopulated scaffold were evident from the albumin and urea production. Expression of Cytokeratin-19 (CK-19), Glucose 6-Phosphatase (G6P), Albumin, Gamma Glutamyl Transferase (GGT) genes has distinctly confirmed the translational signals after the repopulation process. Our study clearly elucidates that the native extracellular matrix of rat liver can be utilized as a scaffold for effective recellularization for whole organ regeneration.

摘要

为了满足器官移植的结构和生理功能需求,对于替代器官的需求不断增加。组织脱细胞和再细胞化有助于保留三维完整性、生化组成、组织超微结构和机械性能,使其在功能上适合器官移植。在此,我们尝试在小型动物模型(Wistar 大鼠)中重建具有潜在转化能力的功能性肝移植物。采用 0.1%SDS(十二烷基硫酸钠)进行脱细胞处理,采用软处理方法,原代肝细胞作为潜在的细胞来源进行再细胞化。通过组织学、DNA 含量、超微结构分析评估和确认脱细胞过程。将大鼠肝细胞重新接种到所得支架上,并通过其代谢功能和基因表达评估其生物相容性。细胞外基质(ECM)的结构成分(层粘连蛋白、I 型胶原、网状蛋白)得以保留,细胞特异性蛋白如 CK-18、甲胎蛋白、白蛋白在再细胞化支架中表达。从白蛋白和尿素的产生可以明显看出,再填充支架的功能和代谢活性。Cytokeratin-19 (CK-19)、葡萄糖 6-磷酸酶(G6P)、白蛋白、γ-谷氨酰转移酶(GGT)基因的表达在再定植过程后明确证实了转化信号。我们的研究清楚地阐明了大鼠肝的固有细胞外基质可以用作整个器官再生的有效再细胞化支架。