Differentiation of Dental Pulp-Derived MSCs into Hepatocyte-Like Cells and Their Therapeutic Use for Chemical Liver Injuries of Rats
Differentiation of Dental Pulp-Derived MSCs into Hepatocyte-Like Cells and Their Therapeutic Use for Chemical Liver Injuries of Rats
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DOI：
10.2485/jhtb.29.215
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发表时间：
2020-10
影响因子：
0.4
通讯作者：
H. Hara;K. Sano;H. Ishikawa;S. Ohkoshi
中科院分区：
文献类型：
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作者：
H. Hara;K. Sano;H. Ishikawa;S. Ohkoshi
：源自牙组织的间充质干细胞（MSC）在再生医学领域受到关注，部分原因是它们可以从乳牙或拔牙中获得。本研究旨在探讨牙髓源性间充质干细胞（DP-MSCs）分化为具有肝细胞功能的细胞的潜力，并探讨这些细胞对大鼠急性化学性肝损伤的治疗作用。使用含有激活素 A 和肝细胞生长因子 (HGF) 的特定试剂培养来自牙髓的 MSC 组分。评估白蛋白、纤维蛋白原和尿素的产生，并通过逆转录 (RT)-PCR 检测它们的特异性 mRNA。还研究了 DP-MSC 对刀豆球蛋白 A (ConA) 和 D-半乳糖胺 (D-gal) 诱导的急性化学损伤大鼠的治疗作用。 DP-MSC 分化为多边形肝细胞样细胞 (HLC)，产生白蛋白并将铵转化为尿素。重要的是，HNF4α（一种肝脏特异性转录因子）在 HLC 中表达，证实了 HLC 的肝脏特异性特性。大鼠肝损伤后，给予 HLC 可显着改善肝功能。因此，DP-MSCs可以分化为具有肝功能的细胞。预计这些细胞在难治性肝病再生医学中的潜在贡献。
: Mesenchymal stem cells (MSCs) derived from dental tissues have gained attention in the field of regenerative medicine, in part because they can be obtained from deciduous or extracted teeth. This study aims to investigate the potential of dental pulp-derived MSCs (DP-MSCs) to differentiate into cells with hepatocyte function and to examine the thera peutic effects of these cells on acute chemical liver injuries of rats. MSC fractions from dental pulp were cultured using specific reagents containing activin A and hepatocyte growth factor (HGF). Albumin, fibrinogen, and urea production were assessed and their specific mRNAs were detected by reverse transcription (RT)-PCR. Therapeutic effects of DP-MSCs on rats with acute chemical injuries induced by concanavalin A (ConA) and D-galactosamine (D-gal) were also investigated. DP-MSCs differentiated into polygonal hepatocyte-like cells (HLCs) that produced albumin and converted ammonium to urea. Importantly, HNF4α, which is a liver-specific transcription factor, was expressed in HLCs, confirming the liver-specif ic properties of HLCs. Administration of HLCs induced significant improvements in liver function following hepatic injury in rats. Thus, DP-MSCs could differentiate into cells with hepatic function. The potential contribution of these cells in re generative medicine for refractory liver diseases is expected.