PIN1 Suppresses the Hepatic Differentiation of Pulp Stem Cells via Wnt3a

Abstract

This study aimed to investigate the role of PIN1 on the hepatic differentiation of human dental pulp stem cells (hDPSCs) and its signaling pathway, as well as the potential therapeutic effects of hDPSC transplantation and PIN1 inhibition on CCl (carbon tetrachloride)-induced liver fibrosis in mice. The in vitro results showed that hepatic differentiation was suppressed by infection with adenovirus-PIN1 and promoted by PIN1 inhibitor juglone via the downregulation of Wnt3a and β-catenin. Compared with treatment with either hDPSC transplantation or juglone alone, the combination of hDPSCs and juglone into CCl-injured mice significantly suppressed liver fibrosis and restored serum levels of alanine transaminase, aspartate transaminase, and ammonia. Collectively, the present study shows for the first time that PIN1 inhibition promotes hepatic differentiation of hDPSCs through the Wnt/β-catenin pathway. Furthermore, juglone in combination with hDPSC transplantation effectively treats liver fibrosis, suggesting that hDPSC transplantation with PIN1 inhibition may be a novel therapeutic candidate for the treatment of liver injury.

Pulp stem cells derived from human permanent and deciduous teeth: Biological characteristics and therapeutic applications

“…Combination with functional innervation and vascularization appears more persuasive for functional pulp regeneration. 107 118 Additionally, predifferentiated PSCs, including hepatocytes, 125 myocytes, 128 osteoblasts, 143 islet-like cell cluster, 45 and keratocytes, 137 Table 3, such as calvarial defect, 110 cerebral ischemia, 116,117 and limbal stem cell deficiency, 38 It was also reported that SHED are capable of differentiating into hepatocyte-like cells directly without fusion in mouse models of carbon tetrachloride-induced liver fibrosis, therefore recovering liver disfunction. 41 In a recent mouse in vivo study, 12…”

“…Differentiated dopaminergic neuron‐like SHED have been reported to survive in striatum of PD mice, significantly improve dopamine level and fiber sprouting in contrast to undifferentiated SHED and enhance neurological recovery . Additionally, predifferentiated PSCs, including hepatocytes, myocytes, osteoblasts, islet‐like cell cluster, and keratocytes, have been administered with therapeutic benefits in animal models for liver fibrosis, muscular dystrophy, calvarial bone defect, diabetes, and corneal trauma, respectively. It is indicated that transplantation of preinduced or predifferentiated PSCs appears more efficacious and more applicable to enhance functional recovery as compared with undifferentiated PSCs.…”

Stem Cell Therapeutics of Acute Liver Diseases, Transplantation, and Regeneration

“…However, for restoration of liver mass after hepatectomy both systemic and coordinated changes are needed in gene expression. These starts guiding regenerative responses, activation of progenitor cells, and proliferation of quiescent hepatocytes [112]. The chronic and repeated liver injuries are caused by alcohol, and HBV, HCV, or other pathogens.…”

“…SOT recipients also face high mortality. Hence, an effective donor screening and prophylaxis should be followed in high-risk SOT recipients to decrease morbidity and mortality [177]. Liver from aged and diseased patients should be avoided.…”

Stem Cells from Cryopreserved Human Dental Pulp Tissues Sequentially Differentiate into Definitive Endoderm and Hepatocyte-Like Cells in vitro

“…The pulp originates from the neural crest of the embryo. hDPSCs readily differentiated into mesenchymal-lineage cells (osteocytes, chondrocytes, and adipocytes) and endodermal-lineage cells (hepatocytes and pancreatic cells), as well as neuro-ectodermal cells 6 , 14 , 16 , 17 , 20 , 21 , 22 . In addition, hDPSCs displayed remarkable functional hepatogenic differentiation potential in vitro and regeneration of injured liver tissues in vivo 2 , 6 , 18 - 22 .…”