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Embryonic Stem Cell-Derived Mesenchymal Stem Cells (MSCs) Have a Superior Neuroprotective Capacity Over Fetal MSCs in the Hypoxic-Ischemic Mouse Brain.胚胎干细胞衍生的间充质干细胞（MSCs）在缺氧缺血性小鼠脑中比胎儿MSCs具有更强的神经保护能力。
Stem Cells Transl Med. 2018 May;7(5):439-449. doi: 10.1002/sctm.17-0260. Epub 2018 Feb 28.
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Episomal plasmid-based generation of induced pluripotent stem cells from fetal femur-derived human mesenchymal stromal cells.基于游离质粒从胎儿股骨来源的人间充质基质细胞生成诱导多能干细胞。
Stem Cell Res. 2016 Jan;16(1):128-32. doi: 10.1016/j.scr.2015.12.013. Epub 2015 Dec 28.
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Increased IL-6 secretion by aged human mesenchymal stromal cells disrupts hematopoietic stem and progenitor cells' homeostasis.衰老的人间充质基质细胞白细胞介素-6分泌增加会破坏造血干细胞和祖细胞的稳态。
Oncotarget. 2016 Mar 22;7(12):13285-96. doi: 10.18632/oncotarget.7690.
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Jaundice, phototherapy and DNA damage in full-term neonates.足月新生儿的黄疸、光疗与DNA损伤
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De Novo Donor-Specific HLA Antibody Formation in Two Patients With Crigler-Najjar Syndrome Type I Following Human Hepatocyte Transplantation With Partial Hepatectomy Preconditioning.两名I型克里格勒-纳贾尔综合征患者在接受部分肝切除预处理的人肝细胞移植后出现新的供者特异性HLA抗体形成。
Am J Transplant. 2016 Mar;16(3):1021-30. doi: 10.1111/ajt.13487. Epub 2015 Nov 2.
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Stem Cell Therapies in Clinical Trials: Progress and Challenges.临床试验中的干细胞疗法：进展与挑战。
Cell Stem Cell. 2015 Jul 2;17(1):11-22. doi: 10.1016/j.stem.2015.06.007.
7
Amelioration of Hyperbilirubinemia in Gunn Rats after Transplantation of Human Induced Pluripotent Stem Cell-Derived Hepatocytes.人诱导多能干细胞来源的肝细胞移植后 Gunn 大鼠高胆红素血症的改善。
Stem Cell Reports. 2015 Jul 14;5(1):22-30. doi: 10.1016/j.stemcr.2015.04.017. Epub 2015 Jun 11.
8
Perivascular Gli1+ progenitors are key contributors to injury-induced organ fibrosis.血管周围Gli1+祖细胞是损伤诱导器官纤维化的关键促成因素。
Cell Stem Cell. 2015 Jan 8;16(1):51-66. doi: 10.1016/j.stem.2014.11.004. Epub 2014 Nov 20.
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Hepatic stellate cells contribute to progenitor cells and liver regeneration.肝星状细胞有助于祖细胞和肝脏再生。
J Clin Invest. 2014 Dec;124(12):5503-15. doi: 10.1172/JCI74119. Epub 2014 Nov 17.
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Gene replacement therapy for genetic hepatocellular jaundice.遗传性肝细胞性黄疸的基因替代治疗。
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人多能干细胞源性间充质干细胞移植支持 Gunn 大鼠肝脏再生。

Transplanted Human Pluripotent Stem Cell-Derived Mesenchymal Stem Cells Support Liver Regeneration in Gunn Rats.

机构信息

Institute for Stem Cell Research and Regenerative Medicine, Neonatolgy and Pediatric Cardiology, Heinrich Heine University, Düsseldorf, Germany.

Clinic of Gastroenterology, Hepatology and Infectious Diseases, and Neonatolgy and Pediatric Cardiology, Heinrich Heine University, Düsseldorf, Germany.

出版信息

Stem Cells Dev. 2018 Dec 15;27(24):1702-1714. doi: 10.1089/scd.2018.0010. Epub 2018 Nov 20.

DOI:10.1089/scd.2018.0010
PMID:30280963
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7366275/
Abstract

Gunn rats bear a mutation within the uridine diphosphate glucuronosyltransferase-1a1 () gene resulting in high serum bilirubin levels as seen in Crigler-Najjar syndrome. In this study, the Gunn rat was used as an animal model for heritable liver dysfunction. Induced mesenchymal stem cells (iMSCs) derived from embryonic stem cells (H1) and induced pluripotent stem cells were transplanted into Gunn rats after partial hepatectomy. The iMSCs engrafted and survived in the liver for up to 2 months. The transplanted iMSCs differentiated into functional hepatocytes as evidenced by partially suppressed hyperbilirubinemia and expression of multiple human-specific hepatocyte markers such as albumin, hepatocyte nuclear factor 4α, , cytokeratin 18, bile salt export pump, multidrug resistance protein 2, Na/taurocholate-cotransporting polypeptide, and α-fetoprotein. These findings imply that transplanted human iMSCs can contribute to liver regeneration in vivo and thus represent a promising tool for the treatment of inherited liver diseases.

摘要

Gunn 大鼠在尿苷二磷酸葡萄糖醛酸转移酶-1a1()基因中发生突变，导致血清胆红素水平升高，类似于克里格勒-纳贾尔综合征。在这项研究中，Gunn 大鼠被用作遗传性肝功能障碍的动物模型。从胚胎干细胞 (H1) 和诱导多能干细胞中诱导产生的间充质干细胞 (iMSCs) 在部分肝切除术后被移植到 Gunn 大鼠体内。iMSCs 植入并在肝脏中存活长达 2 个月。移植的 iMSCs 分化为功能性肝细胞，表现为部分抑制高胆红素血症和多种人特异性肝细胞标志物的表达，如白蛋白、肝细胞核因子 4α、细胞角蛋白 18、胆汁盐输出泵、多药耐药蛋白 2、Na/牛磺胆酸钠共转运多肽和甲胎蛋白。这些发现表明，移植的人 iMSCs 可以促进体内肝再生，因此代表了治疗遗传性肝病的有前途的工具。