Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China.
Department of Interventional & Vascular Surgery, Affiliated Hospital of Nantong University, Nantong 226001, China.
Acta Biochim Biophys Sin (Shanghai). 2023 Apr 20;55(4):601-612. doi: 10.3724/abbs.2023072.
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 , 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 , 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.
肝细胞移植有助于修复肝损伤，但肝细胞资源有限，难以将其常规应用于临床治疗。先前的研究证实，间质干细胞（MSCs）可通过添加不同的细胞因子组合诱导分化为肝样细胞（HLCs），从而发挥部分肝细胞的作用。我们之前的研究发现，干细胞的分化能力与其组织来源密切相关。为了确定最适合肝分化和治疗肝衰竭的间充质干细胞，我们采用三阶段诱导方案，诱导人脂肪来源的间充质干细胞（hADSCs）和脐带间充质干细胞（hUCMSCs）向 HLC 分化，并用急性肝衰竭（ALF）大鼠模型（通过 D-半乳糖诱导）分别评估 MSC 和 MSC 衍生的 HLC（MSCs-HLC）的治疗效果。结果发现，hADSCs 的肝向分化能力强于 hUCMSCs，并且当使用 hADSCs-HLC 或联合使用 hADSCs 和 hADSCs-HLC 时，疗效更好，这对肝细胞再生、肝功能恢复和减轻全身炎症反应具有积极意义，最终提高了急性肝衰竭大鼠的存活率。
