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未分化脂肪组织干细胞移植促进肝再生,改善肝组织病理学损伤,并上调部分肝切除大鼠模型中肝再生及肝脏特异性基因的表达。

Undifferentiated Adipose Tissue Stem Cell Transplantation Promotes Hepatic Regeneration, Ameliorates Histopathologic Damage of the Liver, and Upregulates the Expression of Liver Regeneration- and Liver-Specific Genes in a Rat Model of Partial Hepatectomy.

作者信息

Apostolou Konstantinos G, Papanikolaou Ioannis G, Katselis Charalampos, Feretis Themistoklis, Kletsas Dimitrios, Konstadoulakis Manousos M, Lymperi Maria, Saetta Angelica A, Tsikalakis Spiros, Agrogiannis George, Patsouris Efstratios, Zografos George C, Papalois Apostolos E

机构信息

1st Department of Propaedeutic Surgery, University of Athens, School of Medicine, "Hippocration" Hospital, V. Sofias Avenue 114, 11527 Athens, Greece.

Laboratory of Cell Proliferation & Ageing, National Center for Scientific Research "Demokritos", Neapoleos 27 Street, 15341 Athens, Greece.

出版信息

Stem Cells Int. 2018 Mar 14;2018:1393607. doi: 10.1155/2018/1393607. eCollection 2018.

Abstract

OBJECTIVE

Adipose tissue stem cells (ADSCs) present a promising therapeutic method to alleviate liver failure (LF). The purpose of this prospective study was to evaluate the efficacy of undifferentiated ADSC transplantation on liver regeneration and on the expression of liver regeneration- and liver-specific genes, following 60% partial hepatectomy (PHx).

METHODS

Sixty female rats were subjected to PHx and were transplanted with 10 or 2 × 10 ADSCs, either into the portal vein (PV) or into the hepatic parenchyma. Animals of the control group were not transplanted and served as controls. Animals were sacrificed on the 4th, the 7th, or the 15th postoperative day (POD).

RESULTS

The transplanted ADSCs were successfully engrafted into the liver parenchyma and ameliorated the histopathologic damage on the 7th and 15th POD. All transplanted animals demonstrated a significantly higher liver regeneration rate on the 4th and 7th POD, compared with the control group. The expression of hepatocyte growth factor, -fetoprotein, tyrosine aminotransferase, hepatocyte nuclear factor 4a, and cytochrome P450 1A2 was significantly upregulated, compared with the control group.

CONCLUSIONS

Although undifferentiated, ADSC transplantation significantly enhanced the liver regeneration process. These findings may be proven clinically valuable, especially in cases of acute LF.

摘要

目的

脂肪组织干细胞(ADSCs)为缓解肝衰竭(LF)提供了一种有前景的治疗方法。本前瞻性研究的目的是评估在60%肝部分切除术(PHx)后,未分化的ADSCs移植对肝再生以及肝再生相关基因和肝特异性基因表达的影响。

方法

60只雌性大鼠接受PHx手术,并将10或2×10个ADSCs移植到门静脉(PV)或肝实质内。对照组动物不进行移植,作为对照。在术后第4天、第7天或第15天处死动物。

结果

移植的ADSCs成功植入肝实质,并在术后第7天和第15天改善了组织病理学损伤。与对照组相比,所有移植动物在术后第4天和第7天的肝再生率显著更高。与对照组相比,肝细胞生长因子、甲胎蛋白、酪氨酸转氨酶、肝细胞核因子4α和细胞色素P450 1A2的表达显著上调。

结论

尽管ADSCs未分化,但移植能显著增强肝再生过程。这些发现可能具有临床价值,尤其是在急性肝衰竭病例中。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1e5/5872619/af920a1fb053/SCI2018-1393607.001.jpg

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