Browse > Article
http://dx.doi.org/10.14348/molcells.2018.0060

Characterization of Primary Epithelial Cells Derived from Human Salivary Gland Contributing to in vivo Formation of Acini-like Structures  

Nam, Hyun (Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University)
Kim, Ji-Hye (Laboratory of Molecular Genetics, Dental Research Institute, School of Dentistry, Seoul National University)
Hwang, Ji-Yoon (Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University)
Kim, Gee-Hye (Laboratory of Molecular Genetics, Dental Research Institute, School of Dentistry, Seoul National University)
Kim, Jae-Won (Laboratory of Molecular Genetics, Dental Research Institute, School of Dentistry, Seoul National University)
Jang, Mi (Laboratory of Molecular Genetics, Dental Research Institute, School of Dentistry, Seoul National University)
Lee, Jong-Ho (Department of Oral and Maxillofacial Surgery, School of Dentistry, Seoul National University)
Park, Kyungpyo (Department of Physiology, School of Dentistry, Seoul National University)
Lee, Gene (Laboratory of Molecular Genetics, Dental Research Institute, School of Dentistry, Seoul National University)
Publication Information
Molecules and Cells / v.41, no.6, 2018 , pp. 515-522 More about this Journal
Abstract
Patients with head and neck cancer are treated with therapeutic irradiation, which can result in irreversible salivary gland dysfunction. Because there is no complete cure for such patients, stem cell therapy is an emerging alternative for functional restoration of salivary glands. In this study, we investigated in vitro characteristics of primarily isolated epithelial cells from human salivary gland (Epi-SGs) and in vivo formation of acini-like structures by Epi-SGs. Primarily isolated Epi-SGs showed typical epithelial cell-like morphology and expressed E-cadherin but not N-cadherin. Epi-SGs expressed epithelial stem cell (EpiSC) and embryonic stem cell (ESC) markers. During long-term culture, the expression of EpiSC and ESC markers was highly detected and maintained within the core population with small size and low cytoplasmic complexity. The core population expressed cytokeratin 7 and cytokeratin 14, known as duct markers indicating that Epi-SGs might be originated from the duct. When Epi-SGs were transplanted in vivo with Matrigel, acini-like structures were readily formed at 4 days after transplantation and they were maintained at 7 days after transplantation. Taken together, our data suggested that Epi-SGs might contain stem cells which were positive for EpiSC and ESC markers, and Epi-SGs might contribute to the regeneration of acini-like structures in vivo. We expect that Epi-SGs will be useful source for the functional restoration of damaged salivary gland.
Keywords
acinar and duct; epithelial cell; head and neck cancer; salivary gland; stem cell;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Chen, Z., de Paiva, C.S., Luo, L., Kretzer, F.L., Pflugfelder, S.C., and Li, D.Q. (2004). Characterization of putative stem cell phenotype in human limbal epithelia. Stem Cells 22, 355-366.   DOI
2 De Moerlooze, L., Spencer-Dene, B., Revest, J.M., Hajihosseini, M., Rosewell, I., and Dickson, C. (2000). An important role for the IIIb isoform of fibroblast growth factor receptor 2 (FGFR2) in mesenchymal-epithelial signalling during mouse organogenesis. Development 127, 483-492.
3 de Paiva, C.S., Chen, Z., Corrales, R.M., Pflugfelder, S.C., and Li, D.Q. (2005). ABCG2 transporter identifies a population of clonogenic human limbal epithelial cells. Stem Cells 23, 63-73.   DOI
4 Ema, H., Morita, Y., and Suda, T. (2014). Heterogeneity and hierarchy of hematopoietic stem cells. Exp. Hematol. 42, 74-82 e72.   DOI
5 Feng, J., van der Zwaag, M., Stokman, M.A., van Os, R., and Coppes, R.P. (2009). Isolation and characterization of human salivary gland cells for stem cell transplantation to reduce radiation-induced hyposalivation. Radiother. Oncol. 92, 466-471.   DOI
6 Gorjup, E., Danner, S., Rotter, N., Habermann, J., Brassat, U., Brummendorf, T.H., Wien, S., Meyerhans, A., Wollenberg, B., Kruse, C., et al. (2009). Glandular tissue from human pancreas and salivary gland yields similar stem cell populations. Eur. J. Cell Biol. 88, 409-421.   DOI
7 Huang, H.P., Chen, P.H., Yu, C.Y., Chuang, C.Y., Stone, L., Hsiao, W.C., Li, C.L., Tsai, S.C., Chen, K.Y., Chen, H.F., et al. (2011). Epithelial cell adhesion molecule (EpCAM) complex proteins promote transcription factor-mediated pluripotency reprogramming. J. Biol. Chem. 286, 33520-33532.   DOI
8 Kolle, G., Ho, M., Zhou, Q., Chy, H.S., Krishnan, K., Cloonan, N., Bertoncello, I., Laslett, A.L., and Grimmond, S.M. (2009). Identification of human embryonic stem cell surface markers by combined membrane-polysome translation state array analysis and immunotranscriptional profiling. Stem Cells 27, 2446-2456.   DOI
9 Izumi, K., Tobita, T., and Feinberg, S.E. (2007). Isolation of human oral keratinocyte progenitor/stem cells. J. Dent. Res. 86, 341-346.   DOI
10 Jaskoll, T., Abichaker, G., Witcher, D., Sala, F.G., Bellusci, S., Hajihosseini, M.K., and Melnick, M. (2005). FGF10/FGFR2b signaling plays essential roles during in vivo embryonic submandibular salivary gland morphogenesis. BMC Dev. Biol. 5, 11.   DOI
11 Lombaert, I.M., and Hoffman, M.P. (2010). Epithelial stem/progenitor cells in the embryonic mouse submandibular gland. Front. Oral Biol. 14, 90-106.
12 Lombaert, I.M., Brunsting, J.F., Wierenga, P.K., Faber, H., Stokman, M.A., Kok, T., Visser, W.H., Kampinga, H.H., de Haan, G., and Coppes, R.P. (2008). Rescue of salivary gland function after stem cell transplantation in irradiated glands. PloS one 3, e2063.   DOI
13 Lombaert, I., Movahednia, M.M., Adine, C., and Ferreira, J.N. (2017). Salivary gland regeneration: therapeutic approaches from stem cells to tissue organoids. Stem Cells 35, 97-105.   DOI
14 Pringle, S., Maimets, M., van der Zwaag, M., Stokman, M.A., van Gosliga, D., Zwart, E., Witjes, M.J., de Haan, G., van Os, R., and Coppes, R.P. (2016). Human salivary gland stem cells functionally restore radiation damaged salivary glands. Stem Cells 34, 640-652.   DOI
15 McQualter, J.L., Yuen, K., Williams, B., and Bertoncello, I. (2010). Evidence of an epithelial stem/progenitor cell hierarchy in the adult mouse lung. Proc. Natl. Aca d. Sci. USA 107, 1414-1419.   DOI
16 Nam, H., and Lee, G. (2009). Identification of novel epithelial stem cell-like cells in human deciduous dental pulp. Biochem. Biophys. Res. Commun. 386, 135-139.   DOI
17 Nanduri, L.S., Baanstra, M., Faber, H., Rocchi, C., Zwart, E., de Haan, G., van Os, R., and Coppes, R.P. (2014). Purification and ex vivo expansion of fully functional salivary gland stem cells. Stem Cell Rep. 3, 957-964.   DOI
18 Okita, K., Ichisaka, T., and Yamanaka, S. (2007). Generation of germline-competent induced pluripotent stem cells. Nature 448, 313-317.   DOI
19 Okumura, K., Shinohara, M., and Endo, F. (2012). Capability of tissue stem cells to organize into salivary rudiments. Stem Cells Int. 2012, 502136.
20 Purkis, P.E., Steel, J.B., Mackenzie, I.C., Nathrath, W.B., Leigh, I.M., and Lane, E.B. (1990). Antibody markers of basal cells in complex epithelia. J. Cell Sci. 97(Pt 1), 39-50.
21 Rotter, N., Oder, J., Schlenke, P., Lindner, U., Bohrnsen, F., Kramer, J., Rohwedel, J., Huss, R., Brandau, S., Wollenberg, B., et al. (2008). Isolation and characterization of adult stem cells from human salivary glands. Stem Cells Dev. 17, 509-518.   DOI
22 van Leenders, G., Dijkman, H., Hulsbergen-van de Kaa, C., Ruiter, D., and Schalken, J. (2000). Demonstration of intermediate cells during human prostate epithelial differentiation in situ and in vitro using triple-staining confocal scanning microscopy. Lab. Invest. 80, 1251-1258.   DOI
23 Zhou, S., Schuetz, J.D., Bunting, K.D., Colapietro, A.M., Sampath, J., Morris, J.J., Lagutina, I., Grosveld, G.C., Osawa, M., Nakauchi, H., et al. (2001). The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the sidepopulation phenotype. Nat. Med. 7, 1028-1034.   DOI
24 Vissink, A., Burlage, F.R., Spijkervet, F.K., Jansma, J., and Coppes, R.P. (2003a). Prevention and treatment of the consequences of head and neck radiotherapy. Crit. Rev. Oral Biol. Med. 14, 213-225.   DOI
25 Vissink, A., Jansma, J., Spijkervet, F.K., Burlage, F.R., and Coppes, R.P. (2003b). Oral sequelae of head and neck radiotherapy. Crit. Rev. Oral Biol. Med. 14, 199-212.   DOI