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Human Supernumerary Teeth-Derived Apical Papillary Stem Cells Possess Preferable Characteristics and Efficacy on Hepatic Fibrosis in Mice.

ABSTRACT: Dental tissue has been acknowledged as an advantaged source for high-quality dental pulp stem cell (DPSC) preparation. However, despite the accomplishment of the separation of DPSCs from permanent teeth and supernumerary teeth, the deficiency of rigorous and systematic clarification on the signatures and efficacy will hinder their prospects in regenerative medicine. In this study, we primitively isolated permanent teeth-derived DPSCs and supernumerary teeth-derived apical papillary stem cells (SCAP-Ss) with parental consent. Immunophenotype of DPSCs and SCAP-Ss was determined by a flow cytometry assay, and the cell viability was verified by multidimensional detections including cell proliferation, cell cycle, apoptosis, and senescence. The migration and clonogenic capacity were examined by a wound healing test and crystal violet staining, respectively. The multilineage differentiation potential was quantitated by utilizing Oil Red O staining and Alizarin Red staining, together with real-time PCR analysis. The efficacy on a mouse hepatic fibrosis model was evaluated by using histologic sections and liver function tests. Herein, we showed that SCAP-Ss exhibited comparable immunophenotype and adipogenic differentiation capacity as DPSCs. However, different from DPSCs, SCAP-Ss exhibited superiority in cell viability and osteogenic differentiation. Simultaneously, injection of DPSCs and SCAP-Ss significantly reduced inflammatory infiltration, enhanced liver-associated gene expression, and finally relieved symptoms of hepatic fibrosis. In conclusion, SCAP-Ss possess preferable characteristics and efficacy on hepatic fibrosis in mice. Our findings suggest that SCAP-Ss are an easily accessible postnatal stem cell source with multifaceted characteristics for regenerative medicine.

SUBMITTER: Yao J

PROVIDER: S-EPMC7204141 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Human Supernumerary Teeth-Derived Apical Papillary Stem Cells Possess Preferable Characteristics and Efficacy on Hepatic Fibrosis in Mice.

Yao Jun J Chen Nan N Wang Xiaojing X Zhang Leisheng L Huo Jiali J Chi Ying Y Li Zongjin Z Han Zhongchao Z

Stem cells international 20200130

Dental tissue has been acknowledged as an advantaged source for high-quality dental pulp stem cell (DPSC) preparation. However, despite the accomplishment of the separation of DPSCs from permanent teeth and supernumerary teeth, the deficiency of rigorous and systematic clarification on the signatures and efficacy will hinder their prospects in regenerative medicine. In this study, we primitively isolated permanent teeth-derived DPSCs and supernumerary teeth-derived apical papillary stem cells (S ...[more]

PMID: 32399047

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Project description:A high prevalence of thyroid papillary cancer was reported in hepatitis-C-virus (HCV) positive patients. However, the mechanistic role of hepatic-fibrosis in thyroid malignancy progressions is still unclear.We aimed to study the immune-modulatory interactions between thyroid papillary carcinoma and hepatic-fibrosis.Hepatic-fibrosis was induced in nude-nu-male mice by intra-peritoneal administration of carbon-tetrachloride. To induce thyroid-tumor, a thyroid papillary carcinoma cell line (NPA) was injected subcutaneously in the backs. Fibrotic profile was estimated by α-smooth-muscle-actin (αSMA) expression in liver tissue extracts using western-blots and RT-PCR. Intra-hepatic NK cells were isolated and stained for NK activity (CD107a) by flow cytometry. Liver histopathology (H&E staining), thyroid tumor mass and serum alanine aminotransferase (ALT), serum vascular endothelial growth factor (VEGF) and free-T4 levels were also assessed.Ex-vivo: NPA cells were co-cultured with intra-hepatic NK cells isolated from fibrotic mice with/without the tumor were analyzed for CFSE-proliferations. Both tumor groups (with/without hepatic-fibrosis) excreted higher serum free T4 levels. Hepatic-fibrosis increased tumor weight and size and serum free-T4 levels. In addition, tumor induction increased liver injury (both hepatic-fibrosis, necro-inflammation and serum ALT levels). In addition, tumor-bearing animals with hepatic-fibrosis had increased NK activity. NPA tumor-bearing animals increased fibrosis in spite of increased NK activity; probably due to a direct effect through increased serum free-T4 excretions. Serum VEGF levels were significantly increased in the fibrotic- bearing tumor groups compared to the non-fibrotic groups. In-vitro, NK cells from fibrotic tumor-bearing animals reduced proliferation of NPA cells. This decrease is attributed to increase NK cells activity in the fibrotic animals with the NPA tumors.Our results propose that NK cells although were stimulated in advanced fibrosis with tumor, they lost their anti-tumor and anti-fibrotic activity probably due to secretions of T4 and VEFG and may explain increased risk of thyroid tumors in chronic HCV patients.

Dataset Information

Human Supernumerary Teeth-Derived Apical Papillary Stem Cells Possess Preferable Characteristics and Efficacy on Hepatic Fibrosis in Mice.

Publications

Human Supernumerary Teeth-Derived Apical Papillary Stem Cells Possess Preferable Characteristics and Efficacy on Hepatic Fibrosis in Mice.

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