ABSTRACT
Liver disease is a serious problem affecting millions of people with continually increasing prevalence. Stem cell therapy has become a promising treatment for liver dysfunction. We previously reported on human minor salivary gland mesenchymal stem cells (hMSGMSCs), which are highly self-renewable with multi-potent differentiation capability. In this study, keratinocyte-like cells with self-regeneration and hepatic differentiation potential were isolated and characterized, and named human minor salivary gland epithelial progenitor cells (hMSG-EpiPCs). hMSG-EpiPCs were easily obtained via minor intraoral incision; they expressed epithelial progenitor/stem cell and other tissue stem cell markers such as CD29, CD49f, cytokeratins, ABCG2, PLET-1, salivary epithelial cell markers CD44 and CD166, and the Wnt target related gene LGR5 and LGR6. The cells were induced into functional hepatocytes in vitro which expressed liver-associated markers ALB, CYP3A4, AAT, and CK18. Upon transplantation in vivo, they ameliorated severe acute liver damage in SCID mice caused by carbon tetrachloride (CCl4) injection. In a two-thirds partial hepatectomy mouse model, the transplanted cells survived at least 4 weeks and exhibited hepatic potential. These findings demonstrate that hMSG-EpiPCs have potential as a cellular therapy basis for hepatic diseases, physiological and toxicology studies and regenerative medicine.
Subject(s)
Acute Lung Injury/drug therapy , Cell- and Tissue-Based Therapy , Liver Regeneration/genetics , Mesenchymal Stem Cell Transplantation , Salivary Glands, Minor/transplantation , Acute Lung Injury/chemically induced , Animals , Carbon Tetrachloride/toxicity , Cell Differentiation/genetics , Cell Self Renewal/genetics , Epithelial Cells/transplantation , Gene Expression Regulation, Developmental , Hepatocytes/drug effects , Hepatocytes/pathology , Humans , Liver/growth & development , Liver/metabolism , Mesenchymal Stem Cells/cytology , Mice , Salivary Glands, Minor/cytology , Stem Cells/cytologyABSTRACT
Adult stem cells play an important role in maintaining tissue homeostasis. Although these cells are found in many tissues, the presence of stem cells in the human minor salivary glands is not well explored. Using the explant culture method, we isolated a population of cells with self-renewal and differentiation capacities harboring that reside in the human minor salivary glands, called human minor salivary gland mesenchymal stem cells (hMSGMSCs). These cells show embryonic stem cell and mesenchymal stem cell phenotypes. Our results demonstrate that hMSGMSCs have the potential to undergo mesodermal, ectodermal and endodermal differentiation in conditioned culture systems in vitro. Furthermore, in vivo transplantation of hMSGMSCs into SCID mice after partial hepatectomy shows that hMSGMSCs are able to survive and engraft, characterized by the survival of labeled cells and the expression of the hepatocyte markers AFP and KRT18. These data demonstrate the existence of hMSGMSCs and suggest their potential in cell therapy and regenerative medicine.
