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1.
Arch Toxicol ; 93(12): 3669-3670, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31664497

RESUMO

We wish to submit a corrigendum to the above-mentioned article. Thank you very much for consideration and publication.

2.
Arch Toxicol ; 93(9): 2645-2660, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31435712

RESUMO

Although liver transplantation is a potential effective cure for patients with end-stage liver diseases, this strategy has several drawbacks including high cost, long waiting list, and limited availability of liver organs. Therefore, stem cell-based therapy is presented as an alternative option, which showed promising results in animal models of acute and chronic liver injuries. ABCB5+ cells isolated from skin dermis represent an easy accessible and expandable source of homogenous stem cell populations. In addition, ABCB5+ cells showed already promising results in the treatment of corneal and skin injury. To date, the effect of these cells on liver injury is still unknown. In the current study, sixteen weeks old Mdr2KO mice were i.v. injected with 500,000 ABCB5+ cells using different experimental setups. The effects of cellular therapy on inflammation, fibrosis, apoptosis, and proliferation were analyzed in the collected liver tissues. Toxicity of ABCB5+ cells was additionally investigated in mice with partial liver resection. In vitro, the fibrosis- and inflammatory-modulating effects of supernatant from ABCB5+ cells were examined in the human hepatic stellate cell line (LX-2). Cell injections into fibrotic Mdr2KO mice as well as into mice upon partial liver resection have no signs of toxicity with regard to cell transformation, cellular damage, fibrosis or inflammation as compared to controls. We next investigated the effects of ABCB5+ cells on established biliary liver fibrosis in the Mdr2KO mice. ABCB5+ cells to some extent influenced the shape of the liver inflammatory response and significantly reduced the amount of collagen deposition, as estimated from quantification of sirius red staining. Furthermore, reduced apoptosis and enhanced death compensatory proliferation resulted from ABCB5+ cell transformation. The stem cells secreted several trophic factors that activated TGF-ß family signaling in cultured LX-2 hepatic stellate cells (HSCs), therewith shaping cell fate to an αSMAhigh, Vimentinlow phenotype. Taken together, ABCB5+ cells can represent a safe and feasible strategy to support liver regeneration and to reduce liver fibrosis in chronic liver diseases.


Assuntos
Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Cirrose Hepática/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/metabolismo , Animais , Modelos Animais de Doenças , Células Estreladas do Fígado/citologia , Células Estreladas do Fígado/metabolismo , Humanos , Injeções Intravenosas , Cirrose Hepática/metabolismo , Testes de Função Hepática , Células-Tronco Mesenquimais/citologia , Camundongos Endogâmicos BALB C , Camundongos Knockout , Membro 4 da Subfamília B de Transportadores de Cassetes de Ligação de ATP
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