Stem Cell Reviews and Reports

, Volume 13, Issue 2, pp 258–266 | Cite as

Expression of Desmoglein 2, Desmocollin 3 and Plakophilin 2 in Placenta and Bone Marrow-Derived Mesenchymal Stromal Cells

  • Melanie L. HartEmail author
  • Elisa Rusch
  • Marvin Kaupp
  • Kay Nieselt
  • Wilhelm K. Aicher


Many controversial results exist when comparing mesenchymal stromal cells (MSCs) derived from different sources. Reasons include not only variables in tissue origin, but also methods of cell preparation or choice of expansion media which can strongly influence the expression and hence, function of the cells. In this short report we aimed to investigate the expression of the cell anchoring proteins desmoglein 2, desmocollin 3 and plakophilin 2 in early passage placenta-derived MSCs of fetal (fetal pMSCs) and maternal (maternal pMSCs) origins versus adult bone marrow-derived MSCs (bmMSCs) that were expanded and cultured under the same good manufacturing practice (GMP) conditions. Comprehensive gene expression microarray analysis profiling indicated differential expression of these genes in the different MSC-derived types with fetal pMSCs expressing the highest levels of PKP2, DSC3 and DSG2, followed by maternal pMSCs, while bmMSCs expressed the lowest levels. A higher expression of PKP2 and DSC3 genes in fetal pMSCs was confirmed by qRT-PCR suggesting neonatal increases in the expression of these desmosomal genes vs. adult MSCs. Intracellular desmocollin 3 and desmoglein 2 expression was observed by flow cytometry and cytoplasmic plakophilin 2 by immunofluorescence in all three MSC sources. These data suggest that fetal pMSCs, maternal pMSCs and bmMSCs may anchor intermediate filaments to the plasma membrane via desmocollin 3, desmoglein 2 and plakophilin 2.


Desmosomes Mesenchymal stem cells Mesenchymal stromal cells MSC Desmoglein 2 Desmocollin 3 Plakophilin 2 Placenta Bone marrow 



The authors thank Tanja Abruzzese and Jan. Maerz for their excellent technical support and expert training of the students involved in this project. This study was funded by the DFG (KFO273) and in part by institutional funding.

Compliance with Ethical Standards

Conflict of Interest

The authors indicate no potential conflicts of interest.


  1. 1.
    Delva, E., Tucker, D. K., & Kowalczyk, A. P. (2009). The desmosome. Cold Spring Harbor Perspectives in Biology. doi: 10.1101/cshperspect.a002543.PubMedPubMedCentralGoogle Scholar
  2. 2.
    Kowalczyk, A. P., & Green, K. J. (2013). Structure, function, and regulation of desmosomes. Progress in Molecular Biology and Translational Science. doi: 10.1016/B978-0-12-394311-8.00005-4.PubMedPubMedCentralGoogle Scholar
  3. 3.
    Eshkind, L., Tian, Q., Schmidt, A., Franke, W. W., Windoffer, R., & Leube, R. E. (2002). Loss of desmoglein 2 suggests essential functions for early embryonic development and proliferation of embryonal stem cells. European Journal of Cell Biology. doi: 10.1078/0171-9335-00278.PubMedGoogle Scholar
  4. 4.
    Klingemann, H., Matzilevich, D., & Marchand, J. (2008). Mesenchymal stem cells - sources and clinical applications. Transfusion Medicine and Hemotherapy. doi: 10.1159/000142333.PubMedPubMedCentralGoogle Scholar
  5. 5.
    Rickelt, S., Winter-Simanowski, S., Noffz, E., Kuhn, C., & Franke, W. W. (2009). Upregulation of plakophilin-2 and its acquisition to adherens junctions identifies a novel molecular ensemble of cell-cell-attachment characteristic for transformed mesenchymal cells. International Journal of Cancer. doi: 10.1002/ijc.24552.PubMedGoogle Scholar
  6. 6.
    Wuchter, P., Boda-Heggemann, J., Straub, B. K., Grund, C., Kuhn, C., Krause, U., Seckinger, A., Peitsch, W. K., Spring, H., Ho, A. D., & Franke, W. W. (2007). Processus and recessus adhaerentes: giant adherens cell junction systems connect and attract human mesenchymal stem cells. Cell and Tissue Research. doi: 10.1007/s00441-007-0379-5.PubMedGoogle Scholar
  7. 7.
    Den, Z., Cheng, X., Merched-Sauvage, M., & Koch, P. J. (2006). Desmocollin 3 is required for pre-implantation development of the mouse embryo. Journal of Cell Science. doi: 10.1242/jcs.02769.PubMedGoogle Scholar
  8. 8.
    Grossmann, K. S., Grund, C., Huelsken, J., Behrend, M., Erdmann, B., Franke, W. W., & Birchmeier, W. (2004). Requirement of plakophilin 2 for heart morphogenesis and cardiac junction formation. The Journal of Cell Biology. doi: 10.1083/jcb.200402096.PubMedPubMedCentralGoogle Scholar
  9. 9.
    Bierkamp, C., McLaughlin, K. J., Schwarz, H., Huber, O., & Kemler, R. (1996). Embryonic heart and skin defects in mice lacking plakoglobin. Developmental Biology. doi: 10.1006/dbio.1996.0346.PubMedGoogle Scholar
  10. 10.
    Sacchetti, B., Funari, A., Remoli, C., Giannicola, G., Kogler, G., Liedtke, S., Cossu, G., Serafini, M., Sampaolesi, M., Tagliafico, E., Tenedini, E., Saggio, I., Robey, P. G., Riminucci, M., & Bianco, P. (2016). No identical "mesenchymal stem cells" at different times and sites: human committed progenitors of distinct origin and differentiation potential are incorporated as adventitial cells in microvessels. Stem Cell Reports. doi: 10.1016/j.stemcr.2016.05.011.PubMedPubMedCentralGoogle Scholar
  11. 11.
    Elahi, K. C., Klein, G., Avci-Adali, M., Sievert, K. D., MacNeil, S., & Aicher, W. K. (2016). Human mesenchymal stromal cells from different sources diverge in their expression of cell surface proteins and display distinct differentiation patterns. Stem Cells International. doi: 10.1155/2016/5646384.PubMedGoogle Scholar
  12. 12.
    Ulrich, C., Abruzzese, T., Maerz, J. K., Ruh, M., Amend, B., Benz, K., Rolauffs, B., Abele, H., Hart, M. L., & Aicher, W. K. (2015). Human placenta-derived CD146-positive mesenchymal stromal cells display a distinct osteogenic differentiation potential. Stem Cells and Development. doi: 10.1089/scd.2014.0465.PubMedGoogle Scholar
  13. 13.
    Pilz, G. A., Ulrich, C., Ruh, M., Abele, H., Schäfer, R., Kluba, T., Bühring, H. J., Rolauffs, B., & Aicher, W. K. (2011). Human term placenta-derived mesenchymal stromal cells are less prone to osteogenic differentiation than bone marrow-derived mesenchymal stromal cells. Stem Cells and Development. doi: 10.1089/scd.2010.0308.PubMedGoogle Scholar
  14. 14.
    Ulrich, C., Rolauffs, B., Abele, H., Bonin, M., Nieselt, K., Hart, M. L., & Aicher, W. K. (2013). Low osteogenic differentiation potential of placenta-derived mesenchymal stromal cells correlates with low expression of the transcription factors Runx2 and Twist2. Stem Cells and Development. doi: 10.1089/scd.2012.0693.PubMedPubMedCentralGoogle Scholar
  15. 15.
    Brun, J., Abruzzese, T., Rolauffs, B., Aicher, W. K., & Hart, M. L. (2016). Choice of xenogenic-free expansion media significantly influences the myogenic differentiation potential of human bone marrow-derived mesenchymal stromal cells. Cytotherapy. doi: 10.1016/j.jcyt.2015.11.019.PubMedGoogle Scholar
  16. 16.
    Brun, J., Lutz, K. A., Neumayer, K. M., Klein, G., Seeger, T., Uynuk-Ool, T., Worgotter, K., Schmid, S., Kraushaar, U., Guenther, E., Rolauffs, B., Aicher, W. K., & Hart, M. L. (2015). Smooth muscle-like cells generated from human mesenchymal stromal cells display marker gene expression and electrophysiological competence comparable to bladder smooth muscle cells. PloS One. doi: 10.1371/journal.pone.0145153.Google Scholar
  17. 17.
    Hart, M. L., Brun, J., Lutz, K., Rolauffs, B., & Aicher, W. K. (2014). Do we need standardized, GMP-compliant cell culture procedures for pre-clinical in vitro studies involving mesenchymal stem/stromal cells? Journal of Tissue Science & Engineering. doi: 10.4172/2157-7552.1000135.Google Scholar
  18. 18.
    Pilz, G. A., Braun, J., Ulrich, C., Felka, T., Warstat, K., Ruh, M., Schewe, B., Abele, H., Larbi, A., & Aicher, W. K. (2011). Human mesenchymal stromal cells express CD14 cross-reactive epitopes. Cytometry. doi: 10.1002/cyto.a.21073.PubMedGoogle Scholar
  19. 19.
    Felka, T., Schäfer, R., De Zwart, P., & Aicher, W. K. (2010). Animal serum-free expansion and differentiation of human mesenchymal stromal cells. Cytotherapy. doi: 10.3109/14653240903470647.PubMedGoogle Scholar
  20. 20.
    Nagele, U., Maurer, S., Feil, G., Bock, C., Krug, J., Sievert, K. D., & Stenzl, A. (2008). In vitro investigations of tissue-engineered multilayered urothelium established from bladder washings. European Urology. doi: 10.1016/j.eururo.2008.01.072.Google Scholar
  21. 21.
    Bolstad, B. M., Irizarry, R. A., Astrand, M., & Speed, T. P. (2003). A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics. doi: 10.1093/bioinformatics/19.2.185.PubMedGoogle Scholar
  22. 22.
    Battke, F., Symons, S., & Nieselt, K. (2010). Mayday--integrative analytics for expression data. BMC Bioinformatics. doi: 10.1186/1471-2105-11-121.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Laurence, S., Baskin, S.H. editor: Springer US. (1999). Advances in experimental medicine and Biology series. Advances in Bladder Research. 1 ed.Google Scholar
  24. 24.
    Jost, S.P., Gosling, J.A., Dixon, J.S. (1989). The morphology of normal human bladder urothelium. Journal of Anatomy. PMC1256824.Google Scholar
  25. 25.
    Chen, X., Bonne, S., Hatzfeld, M., van Roy, F., & Green, K. J. (2002). Protein binding and functional characterization of plakophilin 2. Evidence for its diverse roles in desmosomes and beta -catenin signaling. The Journal of Biological Chemistry. doi: 10.1074/jbc.M108765200.PubMedGoogle Scholar
  26. 26.
    Billing, A. M., Ben Hamidane, H., Dib, S. S., Cotton, R. J., Bhagwat, A. M., Kumar, P., Hayat, S., Yousri, N. A., Goswami, N., Suhre, K., Rafii, A., & Graumann, J. (2016). Comprehensive transcriptomic and proteomic characterization of human mesenchymal stem cells reveals source specific cellular markers. Scientific Reports. doi: 10.1038/srep21507.PubMedPubMedCentralGoogle Scholar
  27. 27.
    Roson-Burgo, B., Sanchez-Guijo, F., Del Canizo, C., & De Las Rivas, J. (2014). Transcriptomic portrait of human mesenchymal stromal/stem cells isolated from bone marrow and placenta. BMC Genomics. doi: 10.1186/1471-2164-15-910.Google Scholar
  28. 28.
    Franke, W. W., Rickelt, S., Barth, M., & Pieperhoff, S. (2009). The junctions that don’t fit the scheme: special symmetrical cell-cell junctions of their own kind. Cell and Tissue Research. doi: 10.1007/s00441-009-0849-z.PubMedCentralGoogle Scholar
  29. 29.
    Al-Jassar, C., Bikker, H., Overduin, M., & Chidgey, M. (2013). Mechanistic basis of desmosome-targeted diseases. Journal of Molecular Biology. doi: 10.1016/j.jmb.2013.07.035.PubMedPubMedCentralGoogle Scholar
  30. 30.
    Wahl, J.K., Sacco, P.A., McGranahan-Sadler, T.M., Sauppe, L.M., Wheelock, M.J., Johnson, K.R. (1996). Plakoglobin domains that define its association with the desmosomal cadherins and the classical cadherins: identification of unique and shared domains. Journal of Cell Science. PMID: 8743961.Google Scholar
  31. 31.
    Witcher, L.L., Collins, R., Puttagunta, S., Mechanic, S.E., Munson, M., Gumbiner, B., Cowin, P. (1996). Desmosomal cadherin binding domains of plakoglobin. The Journal of Biological Chemistry. PMID: 8631907.Google Scholar
  32. 32.
    Troyanovsky, S.M., Troyanovsky, R.B., Eshkind, L.G., Leube, R.E., Franke, W.W. (1994). Identification of amino acid sequence motifs in desmocollin, a desmosomal glycoprotein, that are required for plakoglobin binding and plaque formation. Proceedings of the National Academy of Sciences. PMID: 7971964.Google Scholar
  33. 33.
    Bass-Zubek, A. E., Godsel, L. M., Delmar, M., & Green, K. J. (2009). Plakophilins: multifunctional scaffolds for adhesion and signaling. Current Opinion in Cell Biology. doi: 10.1016/ Scholar
  34. 34.
    Calkins, C. C., Hoepner, B. L., Law, C. M., Novak, M. R., Setzer, S. V., Hatzfeld, M., & Kowalczyk, A. P. (2003). The Armadillo Family protein p0071 is a VE-cadherin- and desmoplakin-binding protein. The Journal of Biological Chemistry. doi: 10.1074/jbc.M205693200.Google Scholar
  35. 35.
    Hatzfeld, M., Green, K. J., & Sauter, H. (2003). Targeting of p0071 to desmosomes and adherens junctions is mediated by different protein domains. Journal of Cell Science. doi: 10.1242/jcs.00275.Google Scholar
  36. 36.
    Hofmann, I., Schlechter, T., Kuhn, C., Hergt, M., & Franke, W. W. (2009). Protein p0071 - an armadillo plaque protein that characterizes a specific subtype of adherens junctions. Journal of Cell Science. doi: 10.1242/jcs.043927.PubMedCentralGoogle Scholar
  37. 37.
    Green, K. J., & Gaudry, C. A. (2000). Are desmosomes more than tethers for intermediate filaments? Nature reviews. Molecular Cell Biology. doi: 10.1038/35043032.PubMedGoogle Scholar
  38. 38.
    Getsios, S., Huen, A. C., & Green, K. J. (2004). Working out the strength and flexibility of desmosomes. Nature Reviews. Molecular Cell Biology. doi: 10.1038/nrm1356.PubMedGoogle Scholar
  39. 39.
    Leach, L. (2002). The phenotype of the human materno-fetal endothelial barrier: molecular occupancy of paracellular junctions dictate permeability and angiogenic plasticity. Journal of Anatomy. doi: 10.1046/j.1469-7580.2002.00062.x.Google Scholar
  40. 40.
    Green, K. J., & Simpson, C. L. (2007). Desmosomes: new perspectives on a classic. The Journal of Investigative Dermatology. doi: 10.1038/sj.jid.5701015.Google Scholar
  41. 41.
    Johnson, J. L., Najor, N. A., & Green, K. J. (2014). Desmosomes: regulators of cellular signaling and adhesion in epidermal health and disease. Cold Spring Harbor Perspectives in Medicine. doi: 10.1101/cshperspect.a015297.Google Scholar
  42. 42.
    Khudiakov, A. A., Kostina, D. A., Kostareva, A. A., Tomilin, A. N., & Malashicheva, A. B. (2016). The effect of plakophilin-2 gene mutations on activity of the canonical Wnt signaling pathway. Cells and Tissue Biology. doi: 10.1134/S1990519X16020061.Google Scholar
  43. 43.
    Jin, H. J., Bae, Y. K., Kim, M., Kwon, S. J., Jeon, H. B., Choi, S. J., Kim, S. W., Yang, Y. S., Oh, W., & Chang, J. W. (2013). Comparative analysis of human mesenchymal stem cells from bone marrow, adipose tissue, and umbilical cord blood as sources of cell therapy. International Journal of Molecular Sciences. doi: 10.3390/ijms140917986.Google Scholar
  44. 44.
    Zhang, Z. Y., Teoh, S. H., Chong, M. S., Schantz, J. T., Fisk, N. M., Choolani, M. A., & Chan, J. (2009). Superior osteogenic capacity for bone tissue engineering of fetal compared with perinatal and adult mesenchymal stem cells. Stem Cells. doi: 10.1634/stemcells.2008-0456.Google Scholar
  45. 45.
    Hart, M. L., Kaupp, M., Brun, B., & Aicher, W. K. (2017). Comparative phenotypic transcriptional characterization of human full-term placenta-derived mesenchymal stromal cells compared to bone marrow-derived mesenchymal stromal cells after differentiation in myogenic medium. Placenta. doi: 10.1016/j.placenta.2016.11.007.PubMedGoogle Scholar
  46. 46.
    Maerz, J. K., Roncoroni, L. P., Goldeck, D., Abruzzese, T., Kalbacher, H., Rolauffs, B., DeZwart, P., Nieselt, K., Hart, M. L., Klein, G., & Aicher, W. K. (2016). Bone marrow-derived mesenchymal stromal cells differ in their attachment to fibronectin-derived peptides from term placenta-derived mesenchymal stromal cells. Stem Cell Research & Therapy. doi: 10.1186/s13287-015-0243-6.Google Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Melanie L. Hart
    • 1
    Email author
  • Elisa Rusch
    • 2
  • Marvin Kaupp
    • 2
  • Kay Nieselt
    • 3
  • Wilhelm K. Aicher
    • 2
  1. 1.Laboratory for Cell & Tissue Engineering, Department of Orthopedics and Trauma SurgeryMedical Center - Albert-Ludwigs-University of Freiburg, Faculty of Medicine, Albert-Ludwigs-University of FreiburgFreiburg im BreisgauGermany
  2. 2.Clinical Research Group KFO 273, Department of UrologyUniversity of Tubingen HospitalTubingenGermany
  3. 3.Integrative Transcriptomics, Center for BioinformaticsUniversity of TübingenTübingenGermany

Personalised recommendations