Department of Pediatric Surgery, Reproductive and Developmental Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Department of Child Health, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo Hospital, Jakarta, Indonesia.
J Gastroenterol Hepatol. 2024 Oct;39(10):2190-2196. doi: 10.1111/jgh.16651. Epub 2024 Jun 10.
Even with advancement of medical technologies, liver transplantation still faces several major challenges. Hence, other treatment modalities are urgently needed for patients with end-stage liver disease. Stem cells from human exfoliated deciduous teeth (SHED) was discovered to have highly proliferative and pluripotent properties; including differentiation into hepatocyte-like cells. This study aims to investigate the capability of intrasplenic transplanted SHED and SHED-Hep cells in inducing proliferation of stem cells and native hepatocytes in order to accelerate liver regeneration in liver fibrosis mice models.
Three carbon tetrachloride (CCl)-injured male mice groups were used in this study. Two of those groups were transplanted with either SHED or SHED-Hep, while the other did not undergo transplantation. One age- and sex- matched healthy mice group was used as control. All specimens were immunohistochemically stained with anti-Ki-67 antibodies and anti-proliferating cell nuclear antigen (PCNA) antibodies before counter stained with hematoxylin-eosin.
Anti-Ki-67 antibodies staining: at both 8 and 12 weeks, proliferating activity was predominantly seen on both SHED- and SHED-Hep-transplanted CCl-injured mice groups, while control and non-transplanted CCl-injured mice group showed little to no sign of proliferation activity. Anti-PCNA staining: at both 8 and 12 weeks, significant proliferating activity was detected by PCNA staining, mainly on stem cells population area on SHED- and SHED-Hep-treated group.
In conclusion, this study has provided the evidence that transplantation of SHED or SHED-Hep on liver-injured mice induced proliferation of both transplanted stem cells and native liver cells in order to accelerate liver regeneration.
即使医学技术不断进步，肝移植仍然面临着几个主要挑战。因此，终末期肝病患者急需其他治疗方法。人乳牙脱落干细胞（SHED）具有高度增殖和多能性的特性，包括分化为肝细胞样细胞。本研究旨在探讨脾内移植 SHED 和 SHED-Hep 细胞在诱导肝纤维化小鼠模型中干细胞和固有肝细胞增殖的能力，以加速肝脏再生。
本研究使用了三组雄性 CCl4 损伤的小鼠。其中两组分别接受了 SHED 或 SHED-Hep 移植，而另一组未进行移植。一组年龄和性别匹配的健康小鼠作为对照。所有标本均用抗 Ki-67 抗体和抗增殖细胞核抗原（PCNA）抗体进行免疫组化染色，然后用苏木精-伊红复染。
抗 Ki-67 抗体染色：在 8 周和 12 周时，SHED 和 SHED-Hep 移植的 CCl4 损伤小鼠组均可见明显的增殖活性，而对照和未移植的 CCl4 损伤小鼠组几乎没有增殖活性。抗 PCNA 染色：在 8 周和 12 周时，通过 PCNA 染色检测到明显的增殖活性，主要见于 SHED 和 SHED-Hep 治疗组的干细胞区。
综上所述，本研究提供了证据表明，将 SHED 或 SHED-Hep 移植到肝损伤小鼠中，可诱导移植的干细胞和固有肝细胞增殖，从而加速肝脏再生。
