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

IF 2.6 4区 医学 Q4 CELL & TISSUE ENGINEERING
Regenerative medicine Pub Date : 2025-06-01 Epub Date: 2025-06-30 DOI:10.1080/17460751.2025.2526915
Miyako Tanaka, Kazuaki Tokodai, Kaoru Okada, Masato Sato, Hitomi Okita, Takako Ito, Tetsuro Hoshiai, Masatoshi Saito, Toshio Miki, Michiaki Unno, Takashi Kamei, Masafumi Goto
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引用次数: 0

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.

大鼠门内移植后人羊膜源细胞的凝血活化及肝移植。
目的:人羊膜上皮细胞(hAECs)已成为再生医学中有前途的细胞来源,门内移植是一种潜在的递送途径。然而,haec诱导即刻炎症反应的程度仍不清楚。本研究研究了组织因子(TF)在分离的hAECs中的表达,并在大鼠模型中评估了门内移植后的凝血激活。材料与方法:分析冷冻前后TF表达,测定凝血酶-抗凝血酶(TAT)复合物水平,评价凝血激活情况。为了评估移植和肝细胞样功能,将haec移植到非白蛋白血症大鼠体内,随后进行一系列血清人白蛋白水平测量和肝脏组织学分析。结果:hAECs在低温保存前后均表达TF。门静脉内移植导致血浆TAT水平显著升高,肝素治疗可减轻这种升高。此外,移植后人白蛋白水平升高,第21天肝脏中检测到白蛋白阳性细胞。结论:门静脉内肝移植是一种可行的肝移植方法;然而,TF的表达可能触发凝血激活,可能导致即时血液介导的炎症反应。需要进一步的研究来优化抗凝策略和评估临床应用的长期植入效果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Regenerative medicine
Regenerative medicine 医学-工程:生物医学
CiteScore
4.20
自引率
3.70%
发文量
82
审稿时长
6-12 weeks
期刊介绍: Regenerative medicine replaces or regenerates human cells, tissue or organs, to restore or establish normal function*. Since 2006, Regenerative Medicine has been at the forefront of publishing the very best papers and reviews covering the entire regenerative medicine sector. The journal focusses on the entire spectrum of approaches to regenerative medicine, including small molecule drugs, biologics, biomaterials and tissue engineering, and cell and gene therapies – it’s all about regeneration and not a specific platform technology. The journal’s scope encompasses all aspects of the sector ranging from discovery research, through to clinical development, through to commercialization. Regenerative Medicine uniquely supports this important area of biomedical science and healthcare by providing a peer-reviewed journal totally committed to publishing the very best regenerative medicine research, clinical translation and commercialization. Regenerative Medicine provides a specialist forum to address the important challenges and advances in regenerative medicine, delivering this essential information in concise, clear and attractive article formats – vital to a rapidly growing, multidisciplinary and increasingly time-constrained community. Despite substantial developments in our knowledge and understanding of regeneration, the field is still in its infancy. However, progress is accelerating. The next few decades will see the discovery and development of transformative therapies for patients, and in some cases, even cures. Regenerative Medicine will continue to provide a critical overview of these advances as they progress, undergo clinical trials, and eventually become mainstream medicine.
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