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.
Highlights
Liver dysfunction, which may progress to fulminant or chronic liver failure, is a serious healthcare problem worldwide
Tissue explant method was used for primary cell culture after human minor salivary glands were surgically harvested
The cell population doubling time was 70.85 hours on average, whereas the efficiency of colony formation was 12.3% ± 2.1%. Such results suggest the existence of a population of epithelial progenitor cells derived from human minor salivary glands (hMSG) that could maintain high proliferation capacity during culture in vitro; we named the population as human minor salivary gland epithelial progenitor cells
Summary
Liver dysfunction, which may progress to fulminant or chronic liver failure, is a serious healthcare problem worldwide. Recent studies have attempted to isolate an appropriate source of endodermal adult stem/progenitor cells, such as salivary glands, pancreas, and liver[10,11,12,13,14,15]. Cells from such sources could facilitate the investigation of endodermal organ developmental processes and help to realize cell therapy and tissue engineering-based reconstruction. We reported the existence of both human minor salivary gland mesenchymal stem cells (hMSGMSCs) and epithelial progenitor cells (hMSG-EpiPCs) derived from human labial salivary glands[25,26]. This present study further details the phenotypes and characterization of the epithelial progenitor cells
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