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脂肪来源的基质细胞在肝细胞分化潜能上类似于骨髓基质细胞。

Adipose-derived stromal cells resemble bone marrow stromal cells in hepatocyte differentiation potential and .

机构信息

Department of Gastroenterology, Institute of Geriatrics, Chinese PLA General Hospital, Beijing 100853, China.

Department of Blood Transfusion, Chinese PLA General Hospital, Beijing 100853, China.

出版信息

World J Gastroenterol. 2017 Oct 14;23(38):6973-6982. doi: 10.3748/wjg.v23.i38.6973.

Abstract

AIM

To investigate whether mesenchymal stem cells (MSCs) from adipose-derived stromal cells (ADSCs) and bone marrow stromal cells (BMSCs) have similar hepatic differentiation potential.

METHODS

Mouse ADSCs and BMSCs were isolated and cultured. Their morphological and phenotypic characteristics, as well as their multiple differentiation capacity were compared. A new culture system was established to induce ADSCs and BMSCs into functional hepatocytes. Reverse transcription polymerase chain reaction, Western blot, and immunofluorescence analyses were performed to identify the induced hepatocyte-like cells. CM-Dil-labeled ADSCs and BMSCs were then transplanted into a mouse model of CCl-induced acute liver failure. Fluorescence microscopy was used to track the transplanted MSCs. Liver function was tested by an automatic biochemistry analyzer, and liver tissue histology was observed by hematoxylin and eosin (HE) staining.

RESULTS

ADSCs and BMSCs shared a similar morphology and multiple differentiation capacity, as well as a similar phenotype (with expression of CD29 and CD90 and no expression of CD11b or CD45). Morphologically, ADSCs and BMSCs became round and epithelioid following hepatic induction. These two cell types differentiated into hepatocyte-like cells with similar expression of albumin, cytokeratin 18, cytokeratin 19, alpha fetoprotein, and cytochrome P450. Fluorescence microscopy revealed that both ADSCs and BMSCs were observed in the mouse liver at different time points. Compared to the control group, both the function of the injured livers and HE staining showed significant improvement in the ADSC- and BMSC-transplanted mice. There was no significant difference between the two MSC groups.

CONCLUSION

ADSCs share a similar hepatic differentiation capacity and therapeutic effect with BMSCs in an acute liver failure model. ADSCs may represent an ideal seed cell type for cell transplantation or a bio-artificial liver support system.

摘要

目的

探讨脂肪来源的基质细胞(ADSCs)和骨髓基质细胞(BMSCs)来源的间充质干细胞(MSCs)是否具有相似的肝向分化潜能。

方法

分离培养小鼠 ADSCs 和 BMSCs,比较其形态学和表型特征及多向分化能力。建立新的诱导体系将 ADSCs 和 BMSCs 诱导为功能性肝细胞。采用反转录聚合酶链反应、Western blot 和免疫荧光分析鉴定诱导的肝样细胞。将 CM-Dil 标记的 ADSCs 和 BMSCs 移植到 CCl4 诱导的急性肝衰竭小鼠模型中,荧光显微镜追踪移植的 MSCs。采用自动生化分析仪检测肝功能,苏木精-伊红(HE)染色观察肝组织病理学变化。

结果

ADSCs 和 BMSCs 具有相似的形态和多向分化能力,以及相似的表型(表达 CD29 和 CD90,不表达 CD11b 或 CD45)。肝诱导后,ADSCs 和 BMSCs 形态均变为圆形上皮样细胞。这两种细胞类型均分化为白蛋白、细胞角蛋白 18、细胞角蛋白 19、甲胎蛋白和细胞色素 P450 表达相似的肝样细胞。荧光显微镜显示,在不同时间点,ADSCs 和 BMSCs 均在小鼠肝脏中被观察到。与对照组相比,ADSC 和 BMSC 移植组的受损肝脏功能和 HE 染色均有明显改善,两组 MSC 间无显著差异。

结论

在急性肝衰竭模型中,ADSCs 与 BMSCs 具有相似的肝向分化能力和治疗效果。ADSCs 可能是细胞移植或生物人工肝支持系统的理想种子细胞类型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5121/5658315/05ec2fe93a11/WJG-23-6973-g001.jpg

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