title: A Paracrine Mechanism Accelerating Expansion of Human Induced Pluripotent Stem Cell-Derived Hepatic Progenitor-Like Cells.
abstract: Hepatic stem/progenitor cells in liver development have a high proliferative potential and the ability to differentiate into both hepatocytes and cholangiocytes. In this study, we focused on the cell surface molecules of human induced pluripotent stem (iPS) cell-derived hepatic progenitor-like cells (HPCs) and analyzed how these molecules modulate expansion of these cells. Human iPS cells were differentiated into immature hepatic lineage cells by cytokines. In addition to hepatic progenitor markers (CD13 and CD133), the cells were coimmunostained for various cell surface markers (116 types). The cells were analyzed by flow cytometry and in vitro colony formation culture with feeder cells. Twenty types of cell surface molecules were highly expressed in CD13(+)CD133(+) cells derived from human iPS cells. Of these molecules, CD221 (insulin-like growth factor receptor), which was expressed in CD13(+)CD133(+) cells, was quickly downregulated after in vitro expansion. The proliferative ability was suppressed by a neutralizing antibody and specific inhibitor of CD221. Overexpression of CD221 increased colony-forming ability. We also found that inhibition of CD340 (erbB2) and CD266 (fibroblast growth factor-inducible 14) signals suppressed proliferation. In addition, both insulin-like growth factor (a ligand of CD221) and tumor necrosis factor-like weak inducer of apoptosis (a ligand of CD266) were provided by feeder cells in our culture system. This study revealed the expression profiles of cell surface molecules in human iPS cell-derived HPCs and that the paracrine interactions between HPCs and other cells through specific receptors are important for proliferation.
authors: 1 Laboratory of Stem Cell Therapy, Institute of Innovative Science and Technology, Tokai University , Isehara, Japan .|2 Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Tokai University , Isehara, Japan .
authors: Kota
authors: K
authors: Tsuruya
authors: 1 Laboratory of Stem Cell Therapy, Institute of Innovative Science and Technology, Tokai University , Isehara, Japan .
authors: Hiromi
authors: H
authors: Chikada
authors: 1 Laboratory of Stem Cell Therapy, Institute of Innovative Science and Technology, Tokai University , Isehara, Japan .
authors: Kinuyo
authors: K
authors: Ida
authors: 1 Laboratory of Stem Cell Therapy, Institute of Innovative Science and Technology, Tokai University , Isehara, Japan .|2 Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Tokai University , Isehara, Japan .
authors: Kazuya
authors: K
authors: Anzai
authors: 2 Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Tokai University , Isehara, Japan .
authors: Tatehiro
authors: T
authors: Kagawa
authors: 3 Department of Regenerative Medicine, School of Medicine and Center for Matrix Biology and Medicine, Graduate School of Medicine, Tokai University , Isehara, Japan .
authors: Yutaka
authors: Y
authors: Inagaki
authors: 2 Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Tokai University , Isehara, Japan .
authors: Tetsuya
authors: T
authors: Mine
authors: 1 Laboratory of Stem Cell Therapy, Institute of Innovative Science and Technology, Tokai University , Isehara, Japan .
authors: Akihide
authors: A
authors: Kamiya
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001652:Bile Ducts / Q000166:cytology*; D015415:Biomarkers / Q000378:metabolism; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D016207:Cytokines / Q000494:pharmacology; D061252:Feeder Cells / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000037:antagonists & inhibitors; D005434:Flow Cytometry; D022781:Hepatocytes / Q000166:cytology*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis; D017451:Receptors, Somatomedin / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D013002:Somatomedins / Q000378:metabolism; D000074050:TWEAK Receptor
chemical_list: D015415:Biomarkers; D016207:Cytokines; D005346:Fibroblast Growth Factors; D008565:Membrane Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D017526:Receptor, IGF Type 1; D017451:Receptors, Somatomedin; D018124:Receptors, Tumor Necrosis Factor; D013002:Somatomedins; D000074050:TWEAK Receptor; C000613297:TNFRSF12A protein, human; C112971:fibroblast growth factor 14