Adipose-derived stem cells show hepatic differentiation potential and therapeutic effect in rats with acute liver failure.

Adipose-derived stem cells show hepatic differentiation potential and therapeutic effect in rats with acute liver failure.
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DOI:
10.3724/abbs.2023072
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发表时间:
2023-04-20
影响因子:
3.7
通讯作者:
Zhang X
Zhang X
中科院分区:
生物学3区
文献类型:
--
作者:
Jin Y;Shi R;Qi T;Li Q;Chen C;Gao S;Gao F;Yang D;Sun G;Xu J;Fu Q;Xu J;Zhang X

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肝细胞移植有助于肝损伤的修复,但肝细胞资源有限,难以成为常规治疗方法。已有研究证实,在体外加入不同的细胞因子组合可以诱导间充质干细胞(mesenchymalstemcells,MSCs)分化为肝细胞样细胞(hepatocyte-like cells,HLC),并发挥肝细胞的某些功能。我们前期的研究发现,干细胞的分化能力与组织的来源密切相关。为了鉴定最适合肝脏分化和治疗肝功能衰竭的间充质干细胞,我们使用三阶段诱导过程,其中在体外诱导人脂肪来源的干细胞(hADSCs)和脐带间充质干细胞(hUCMSCs)向HLCs分化,并且用MSC和MSC来源的HLCs治疗由D-半乳糖诱导的急性肝功能衰竭(ALF)大鼠(MSCs-HLC)。我们发现hADSCs的肝分化能力强于hUCMSCs,单独使用hADSCs-HLC或联合使用hADSCs-HLC具有更好的疗效,对肝细胞再生、肝功能恢复和减轻全身炎症反应具有积极意义,最终提高急性肝衰竭大鼠的存活率。
Hepatocyte transplantation contributes to the repair of liver damage, but hepatocyte resources are limited, making it difficult for this to become a routine treatment. Previous studies have confirmed that mesenchymal stem cells (MSCs) can be induced to differentiate into hepatocyte-like cells (HLCs) by adding different cytokine combinations in vitro, and they then play some roles of hepatocytes. Our previous studies found that the differentiation ability of stem cells is closely related to the origin of the tissue. To identify the mesenchymal stem cells that are most suitable for hepatic differentiation and the treatment of liver failure, we use a three-phase induction process in which human adipose-derived stem cells (hADSCs) and umbilical cord mesenchymal stem cells (hUCMSCs) are induced to differentiate towards HLCs in vitro, and rats with acute liver failure (ALF) induced by D-gal are cured by MSCs and MSC-derived HLCs (MSCs-HLC), respectively. We find that hADSCs are stronger than hUCMSCs in hepatic differentiation ability, and they have a better curative effect when using hADSCs-HLC or jointly using hADSCs and hADSCs-HLC, which has positive significance for hepatocyte regeneration, recovery of liver function and reduction of systemic inflammatory reaction, finally improving the survival rate of rats with acute liver failure.
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