Abstract

BackgroundTissue-specific stem/progenitor cells are found in various adult tissues and may have the capacity for lineage-specific differentiation, facilitating applications in autologous transplantation. Stage-specific embryonic antigen 4 (SSEA-4), an early embryonic glycolipid antigen, is expressed in cells derived from adult human pancreas exocrine tissue. Here, we examined the characteristics and lineage-specific differentiation capacity of SSEA-4+ cells.MethodsHuman adult partial pancreas tissues were obtained from different donors and cultured in vitro. SSEA-4+ and CA19-9+ cells were isolated from adult human pancreas exocrine cells using magnetic-activated cell sorting, and gene expression was validated by quantitative polymerase chain reaction. To confirm in-vivo differentiation, SSEA-4+ and CA19-9+ cells were transplanted into the dorsal subcutaneous region of mice. Finally, morphological features of differentiated areas were confirmed by immunostaining and morphometric analysis.ResultsSSEA-4-expressing cells were detected in isolated pancreas exocrine cells from adult humans. These SSEA-4+ cells exhibited coexpression of CA19-9, a marker of pancreatic duct cells, but not amylase expression, as shown by immunostaining and flow cytometry. SSEA-4+ cells exhibited higher relative expression of Oct4, Nanog, Klf4, Sox2, and c-Myc mRNAs than CA19-9+ cells. Pancreatic intralobular ducts (PIDs) were generated from SSEA-4+ or CA19-9+ cells in vivo at 5 weeks after transplantation. However, newly formed PIDs from CA19-9+ cells were less abundant and showed an incomplete PID morphology. In contrast, newly formed PIDs from SSEA-4+ cells were abundant in the transplanted area and showed a crowded morphology, typical of PIDs. Sox9 and Ngn3, key transcription factors associated with pancreatic development and regeneration, were expressed in PIDs from SSEA-4+ cells.ConclusionsSSEA-4-expressing cells in the adult human pancreas may have the potential for regeneration of the pancreas and may be used as a source of stem/progenitor cells for pancreatic cell lineage-specific differentiation.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-016-0422-0) contains supplementary material, which is available to authorized users.

Highlights

  • Tissue-specific stem/progenitor cells are found in various adult tissues and may have the capacity for lineage-specific differentiation, facilitating applications in autologous transplantation

  • We hypothesized that Stage-specific embryonic antigen 4 (SSEA-4) may be used as a marker of adult human pancreatic progenitor cells and that SSEA-4+ cells may have the capacity for differentiation

  • We focused on the differentiation capacity and regenerating activity of cells expressing SSEA-4 and cells, these Pancreatic intralobular duct (PID) formed in smaller areas than those in the group transplanted with SSEA-4+ cells and showed lower expression of Sox9 and Ngn3

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Summary

Introduction

Tissue-specific stem/progenitor cells are found in various adult tissues and may have the capacity for lineage-specific differentiation, facilitating applications in autologous transplantation. Stage-specific embryonic antigen 4 (SSEA-4), an early embryonic glycolipid antigen, is expressed in cells derived from adult human pancreas exocrine tissue. ES cells are present and have the capacity to differentiate into any cell type only in the embryonic development stage. Some cells expressing ES cellspecific markers, such as Oct, Nanog, and stage-specific embryonic antigen 4 (SSEA-4), have been identified in cord blood [9] and the adult pancreas [10]. The ES-like cells identified in adult tissue do not have all of the characteristic features of ES cells but still have the ability to differentiate into specific cells. Many researchers have studied the applications of ES-like cells isolated from adult tissues in regenerative therapies for a variety of diseases [11,12,13,14]

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