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大鼠门静脉内移植后人羊膜来源细胞的凝血激活与肝内植入

Coagulation activation and hepatic engraftment of human amnion-derived cells after intraportal transplantation in rats.

作者信息

Tanaka Miyako, Tokodai Kazuaki, Okada Kaoru, Sato Masato, Okita Hitomi, Ito Takako, Hoshiai Tetsuro, Saito Masatoshi, Miki Toshio, Unno Michiaki, Kamei Takashi, Goto Masafumi

机构信息

Department of Surgery, Tohoku University, Sendai, Japan.

Transplantation and Regenerative Medicine Center, Tohoku University Hospital, Sendai, Japan.

出版信息

Regen Med. 2025 Jun 30:1-11. doi: 10.1080/17460751.2025.2526915.

Abstract

AIMS

Human amniotic epithelial cells (hAECs) have emerged as a promising cell source for regenerative medicine, with intraportal transplantation as a potential delivery route. However, the extent to which hAECs induce an immediate inflammatory response remains unclear. This study investigated tissue factor (TF) expression in isolated hAECs and assessed coagulation activation following intraportal transplantation in a rat model.

MATERIALS AND METHODS

TF expression was analyzed before and after cryopreservation, while thrombin - antithrombin (TAT) complex levels were measured to evaluate coagulation activation. To assess engraftment and hepatocyte-like function, hAECs were transplanted into non-albuminemic rats, followed by serial measurements of serum human albumin levels and histological liver analysis.

RESULTS

The findings indicate that hAECs express TF pre- and post-cryopreservation. Intraportal transplantation resulted in a significant increase in plasma TAT levels, which was mitigated by heparin administration. Furthermore, human albumin levels increased post-transplantation, and albumin-positive cells were detected in the liver on day 21.

CONCLUSION

These results suggest that intraportal hAEC transplantation is a feasible approach for hepatic engraftment; however, TF expression may trigger coagulation activation, potentially leading to an instant blood-mediated inflammatory reaction. Further research is warranted to optimize anticoagulation strategies and evaluate long-term engraftment efficacy for clinical applications.

摘要

目的

人羊膜上皮细胞(hAECs)已成为再生医学中一种有前景的细胞来源,门静脉内移植是一种潜在的递送途径。然而,hAECs引发即时炎症反应的程度仍不清楚。本研究调查了分离的hAECs中组织因子(TF)的表达,并评估了大鼠模型门静脉内移植后的凝血激活情况。

材料与方法

分析冻存前后的TF表达,同时测量凝血酶 - 抗凝血酶(TAT)复合物水平以评估凝血激活。为评估植入和肝细胞样功能,将hAECs移植到无白蛋白血症大鼠体内,随后连续测量血清人白蛋白水平并进行肝脏组织学分析。

结果

研究结果表明,hAECs在冻存前后均表达TF。门静脉内移植导致血浆TAT水平显著升高,肝素给药可减轻这种升高。此外,移植后人类白蛋白水平升高,在第21天肝脏中检测到白蛋白阳性细胞。

结论

这些结果表明门静脉内hAEC移植是肝脏植入的一种可行方法;然而,TF表达可能触发凝血激活,潜在导致即时血液介导的炎症反应。有必要进一步研究以优化抗凝策略并评估临床应用中的长期植入效果。

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