DOI QR코드

DOI QR Code

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)
  • 투고 : 2017.04.18
  • 심사 : 2018.03.24
  • 발행 : 2018.06.30

초록

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.

키워드

참고문헌

  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. https://doi.org/10.1634/stemcells.22-3-355
  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. https://doi.org/10.1634/stemcells.2004-0093
  4. Ema, H., Morita, Y., and Suda, T. (2014). Heterogeneity and hierarchy of hematopoietic stem cells. Exp. Hematol. 42, 74-82 e72. https://doi.org/10.1016/j.exphem.2013.11.004
  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. https://doi.org/10.1016/j.radonc.2009.06.023
  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. https://doi.org/10.1016/j.ejcb.2009.02.187
  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. https://doi.org/10.1074/jbc.M111.256164
  8. Izumi, K., Tobita, T., and Feinberg, S.E. (2007). Isolation of human oral keratinocyte progenitor/stem cells. J. Dent. Res. 86, 341-346. https://doi.org/10.1177/154405910708600408
  9. 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. https://doi.org/10.1186/1471-213X-5-11
  10. 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. https://doi.org/10.1002/stem.182
  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. https://doi.org/10.1371/journal.pone.0002063
  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. https://doi.org/10.1002/stem.2455
  14. 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. https://doi.org/10.1073/pnas.0909207107
  15. 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. https://doi.org/10.1016/j.bbrc.2009.05.141
  16. 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. https://doi.org/10.1016/j.stemcr.2014.09.015
  17. Okita, K., Ichisaka, T., and Yamanaka, S. (2007). Generation of germline-competent induced pluripotent stem cells. Nature 448, 313-317. https://doi.org/10.1038/nature05934
  18. Okumura, K., Shinohara, M., and Endo, F. (2012). Capability of tissue stem cells to organize into salivary rudiments. Stem Cells Int. 2012, 502136.
  19. 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. https://doi.org/10.1002/stem.2278
  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. https://doi.org/10.1089/scd.2007.0180
  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. https://doi.org/10.1038/labinvest.3780133
  23. 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. https://doi.org/10.1177/154411130301400306
  24. 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. https://doi.org/10.1177/154411130301400305
  25. 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. https://doi.org/10.1038/nm0901-1028

피인용 문헌

  1. Immortalization of Salivary Gland Epithelial Cells of Xerostomic Patients: Establishment and Characterization of Novel Cell Lines vol.9, pp.12, 2020, https://doi.org/10.3390/jcm9123820
  2. The Alteration of Salivary Immunoglobulin A in Autism Spectrum Disorders vol.12, pp.None, 2021, https://doi.org/10.3389/fpsyt.2021.669193