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Unravelling the Pluripotency Paradox in Fetal and Placental Mesenchymal Stem Cells: Oct-4 Expression and the Case of the Emperor’s New Clothes

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Abstract

Mesenchymal stem cells (MSC) from fetal-placental tissues have translational advantages over their adult counterparts, and have variably been reported to express pluripotency markers. OCT- 4 expression in fetal-placental MSC has been documented in some studies, paradoxically without tumourogenicity in vivo. It is possible that OCT- 4 expression is insufficient to induce true “stemness”, but this issue is important for the translational safety of fetal-derived MSC. To clarify this, we undertook a systematic literature review on OCT- 4 in fetal or adnexal MSC to show that most studies report OCT- 4 message or protein expression, but no study provides definitive evidence of true OCT- 4A expression. Discrepant findings were attributable not to different culture conditions, tissue sources, or gestational ages but instead to techniques used. In assessing OCT- 4 as a pluripotency marker, we highlight the challenges in detecting the correct OCT- 4 isoform (OCT- 4A) associated with pluripotency. Although specific detection of OCT- 4A mRNA is achievable, it appears unlikely that any antibody can reliably distinguish between OCT- 4A and the pseudogene OCT- 4B. Finally, using five robust techniques we demonstrate that fetal derived-MSC do not express OCT- 4A (or by default OCT- 4B). Reports suggesting OCT- 4 expression in fetal-derived MSC warrant reassessment, paying attention to gene and protein isoforms, pseudogenes, and antibody choice as well as primer design. Critical examination of the OCT- 4 literature leads us to suggest that OCT- 4 expression in fetal MSC may be a case of “The Emperor’s New Clothes” with early reports of (false) positive expression amplified in subsequent studies without critical attention to emerging refinements in knowledge and methodology.

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References

  1. Aguilar, S., Nye, E., Chan, J., et al. (2007). Murine but not human mesenchymal stem cells generate osteosarcoma-like lesions in the lung. Stem Cells, 25(6), 1586–1594.

    Article  PubMed  Google Scholar 

  2. Alviano, F., Fossati, V., Marchionni, C., et al. (2007). Term Amniotic membrane is a high throughput source for multipotent Mesenchymal Stem Cells with the ability to differentiate into endothelial cells in vitro. BMC Dev Biol, 7(11).

  3. Atlasi, Y., Mowla, S. J., Ziaee, S. A., Gokhale, P. J., & Andrews, P. W. (2008). OCT4 spliced variants are differentially expressed in human pluripotent and nonpluripotent cells. Stem Cells, 26(12), 3068–3074.

    Article  PubMed  CAS  Google Scholar 

  4. Avanzini, M. A., Bernardo, M. E., Cometa, A. M., et al. (2009). Generation of mesenchymal stromal cells in the presence of platelet lysate: a phenotypic and functional comparison of umbilical cord blood- and bone marrow-derived progenitors. Haematologica, 94(12), 1649–1660.

    Article  PubMed  CAS  Google Scholar 

  5. Battula, V. L., Bareiss, P. M., Treml, S., et al. (2007). Human placenta and bone marrow derived MSC cultured in serum-free, b-FGF-containing medium express cell surface frizzled-9 and SSEA-4 and give rise to multilineage differentiation. Differentiation, 75(4), 279–291.

    Article  PubMed  CAS  Google Scholar 

  6. Bieback, K., Kern, S., Kluter, H., & Eichler, H. (2004). Critical parameters for the isolation of mesenchymal stem cells from umbilical cord blood. Stem Cells, 22(4), 625–634.

    Article  PubMed  Google Scholar 

  7. Booth, H. A., & Holland, P. W. (2004). Eleven daughters of NANOG. Genomics, 84(2), 229–238.

    Article  PubMed  CAS  Google Scholar 

  8. Bossolasco, P., Montemurro, T., Cova, L., et al. (2006). Molecular and phenotypic characterization of human amniotic fluid cells and their differentiation potential. Cell Research, 16(4), 329–336.

    Article  PubMed  CAS  Google Scholar 

  9. Boyer, L. A., Lee, T. I., Cole, M. F., et al. (2005). Core transcriptional regulatory circuitry in human embryonic stem cells. Cell, 122(6), 947–956.

    Article  PubMed  CAS  Google Scholar 

  10. Broxmeyer, H. E. (2010). Umbilical cord transplantation: epilogue. Seminars in Hematology, 47(1), 97–103.

    Article  PubMed  Google Scholar 

  11. Campagnoli, C., Roberts, I. A., Kumar, S., Bennett, P. R., Bellantuono, I., & Fisk, N. M. (2001). Identification of mesenchymal stem/progenitor cells in human first-trimester fetal blood, liver, and bone marrow. Blood, 98(8), 2396–2402.

    Article  PubMed  CAS  Google Scholar 

  12. Carlin, R., Davis, D., Weiss, M., Schultz, B., Troyer, D. (2006). Expression of early transcription factors OCT- 4, Sox-2 and Nanog by porcine umbilical cord (PUC) matrix cells. Reprod Biol Endocrinol, 4(8).

  13. Cauffman, G., Liebaers, I., Van Steirteghem, A., & Van de Velde, H. (2006). POU5F1 isoforms show different expression patterns in human embryonic stem cells and preimplantation embryos. Stem Cells, 24(12), 2685–2691.

    Article  PubMed  CAS  Google Scholar 

  14. Chan, J., O’Donoghue, K., Gavina, M., et al. (2006). Galectin-1 induces skeletal muscle differentiation in human fetal mesenchymal stem cells and increases muscle regeneration. Stem Cells, 24(8), 1879–1891.

    Article  PubMed  CAS  Google Scholar 

  15. Chan, J., Waddington, S. N., O’Donoghue, K., et al. (2007). Widespread distribution and muscle differentiation of human fetal mesenchymal stem cells after intrauterine transplantation in dystrophic mdx mouse. Stem Cells, 25(4), 875–884.

    Article  PubMed  CAS  Google Scholar 

  16. Chang, Y. J., Hwang, S. M., Tseng, C. P., et al. (2010). Isolation of mesenchymal stem cells with neurogenic potential from the mesoderm of the amniotic membrane. Cells, Tissues, Organs, 192(2), 93–105.

    Article  PubMed  Google Scholar 

  17. Conconi, M. T., Burra, P., Di Liddo, R., et al. (2006). CD105(+) cells from Wharton’s jelly show in vitro and in vivo myogenic differentiative potential. International Journal of Molecular Medicine, 18(6), 1089–1096.

    PubMed  CAS  Google Scholar 

  18. Crisan, M., Yap, S., Casteilla, L., et al. (2008). A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell, 3(3), 301–313.

    Article  PubMed  CAS  Google Scholar 

  19. De Coppi, P., Bartsch, G., Jr., Siddiqui, M. M., et al. (2007). Isolation of amniotic stem cell lines with potential for therapy. Nature Biotechnology, 25(1), 100–106.

    Article  PubMed  CAS  Google Scholar 

  20. de Jong, J., & Looijenga, L. H. (2006). Stem cell marker OCT3/4 in tumor biology and germ cell tumor diagnostics: history and future. Critical Reviews in Oncogenesis, 12(3–4), 171–203.

    Article  PubMed  Google Scholar 

  21. Dominici, M., Le Blanc, K., Mueller, I., et al. (2006). Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy, 8(4), 315–317.

    Article  PubMed  CAS  Google Scholar 

  22. Erices, A., Conget, P., & Minguell, J. J. (2000). Mesenchymal progenitor cells in human umbilical cord blood. British Journal of Haematology, 109(1), 235–242.

    Article  PubMed  CAS  Google Scholar 

  23. Ersek, A., Pixley, J. S., Goodrich, A. D., et al. (2010). Persistent circulating human insulin in sheep transplanted in utero with human mesenchymal stem cells. Experimental Hematology, 38(4), 311–320.

    Article  PubMed  CAS  Google Scholar 

  24. Fariha, M. M., Chua, K. H., Tan, G. C., Tan, A. E., & Hayati, A. R. (2011). Human chorion-derived stem cells: changes in stem cell properties during serial passage. Cytotherapy, 13(5), 582–593.

    Article  PubMed  CAS  Google Scholar 

  25. Fong, C. Y., Chak, L. L., Biswas, A., et al. (2011). Human Wharton’s jelly stem cells have unique transcriptome profiles compared to human embryonic stem cells and other mesenchymal stem cells. Stem Cell Reviews, 7(1), 1–16.

    Article  PubMed  CAS  Google Scholar 

  26. Fong, C. Y., Richards, M., Manasi, N., Biswas, A., & Bongso, A. (2007). Comparative growth behaviour and characterization of stem cells from human Wharton’s jelly. Reproductive Biomedicine Online, 15(6), 708–718.

    Article  PubMed  CAS  Google Scholar 

  27. Fukuchi, Y., Nakajima, H., Sugiyama, D., Hirose, I., Kitamura, T., & Tsuji, K. (2004). Human placenta-derived cells have mesenchymal stem/progenitor cell potential. Stem Cells, 22(5), 649–658.

    Article  PubMed  CAS  Google Scholar 

  28. Gonzalez, R., Maki, C. B., Pacchiarotti, J., et al. (2007). Pluripotent marker expression and differentiation of human second trimester Mesenchymal Stem Cells. Biochemical and Biophysical Research Communications, 362(2), 491–497.

    Article  PubMed  CAS  Google Scholar 

  29. Gotherstrom, C., Ringden, O., Tammik, C., Zetterberg, E., Westgren, M., & Le Blanc, K. (2004). Immunologic properties of human fetal mesenchymal stem cells. American Journal of Obstetrics and Gynecology, 190(1), 239–245.

    Article  PubMed  CAS  Google Scholar 

  30. Greco, S. J., Liu, K., & Rameshwar, P. (2007). Functional similarities among genes regulated by OCT4 in human mesenchymal and embryonic stem cells. Stem Cells, 25(12), 3143–3154.

    Article  PubMed  CAS  Google Scholar 

  31. Guillot, P. V., Abass, O., Bassett, J. H., et al. (2008). Intrauterine transplantation of human fetal mesenchymal stem cells from first-trimester blood repairs bone and reduces fractures in osteogenesis imperfecta mice. Blood, 111(3), 1717–1725.

    Article  PubMed  CAS  Google Scholar 

  32. Guillot, P. V., Gotherstrom, C., Chan, J., Kurata, H., & Fisk, N. M. (2007). Human first-trimester fetal MSC express pluripotency markers and grow faster and have longer telomeres than adult MSC. Stem Cells, 25(3), 646–654.

    Article  PubMed  CAS  Google Scholar 

  33. Guillot, P. V., O’Donoghue, K., Kurata, H., & Fisk, N. M. (2006). Fetal stem cells: betwixt and between. Seminars in Reproductive Medicine, 24(5), 340–347.

    Article  PubMed  CAS  Google Scholar 

  34. Hoynowski, S. M., Fry, M. M., Gardner, B. M., et al. (2007). Characterization and differentiation of equine umbilical cord-derived matrix cells. Biochemical and Biophysical Research Communications, 362(2), 347–353.

    Article  PubMed  CAS  Google Scholar 

  35. Hu, Y., Liao, L., Wang, Q., et al. (2003). Isolation and identification of mesenchymal stem cells from human fetal pancreas. The Journal of Laboratory and Clinical Medicine, 141(5), 342–349.

    Article  PubMed  CAS  Google Scholar 

  36. Huang, Y. C., Yang, Z. M., Chen, X. H., et al. (2009). Isolation of mesenchymal stem cells from human placental decidua basalis and resistance to hypoxia and serum deprivation. Stem Cell Reviews, 5(3), 247–255.

    Article  PubMed  CAS  Google Scholar 

  37. Igura, K., Zhang, X., Takahashi, K., Mitsuru, A., Yamaguchi, S., & Takashi, T. A. (2004). Isolation and characterization of mesenchymal progenitor cells from chorionic villi of human placenta. Cytotherapy, 6(6), 543–553.

    Article  PubMed  CAS  Google Scholar 

  38. In’t Anker, P. S., Noort, W. A., Scherjon, S. A., et al. (2003). Mesenchymal stem cells in human second-trimester bone marrow, liver, lung, and spleen exhibit a similar immunophenotype but a heterogeneous multilineage differentiation potential. Haematologica, 88(8), 845–852.

    Google Scholar 

  39. In’t Anker, P. S., Scherjon, S. A., Kleijburg-van der Keur, C., et al. (2003). Amniotic fluid as a novel source of mesenchymal stem cells for therapeutic transplantation. Blood, 102(4), 1548–1549.

    Article  Google Scholar 

  40. Jiang, R., Han, Z., Zhuo, G., et al. (2011). Transplantation of placenta-derived mesenchymal stem cells in type 2 diabetes: a pilot study. Front Med, 5(1), 94–100.

    Article  PubMed  Google Scholar 

  41. Jo, C. H., Kim, O. S., Park, E. Y., et al. (2008). Fetal mesenchymal stem cells derived from human umbilical cord sustain primitive characteristics during extensive expansion. Cell and Tissue Research, 334(3), 423–433.

    Article  PubMed  Google Scholar 

  42. Kaltz, N., Funari, A., Hippauf, S., et al. (2008). In vivo osteoprogenitor potency of human stromal cells from different tissues does not correlate with expression of POU5F1 or its pseudogenes. Stem Cells, 26(9), 2419–2424.

    Article  PubMed  CAS  Google Scholar 

  43. Kennea, N. L., Waddington, S. N., Chan, J., et al. (2009). Differentiation of human fetal mesenchymal stem cells into cells with an oligodendrocyte phenotype. Cell Cycle, 8(7), 1069–1079.

    Article  PubMed  CAS  Google Scholar 

  44. Kermani, A. J., Fathi, F., & Mowla, S. J. (2008). Characterization and genetic manipulation of human umbilical cord vein mesenchymal stem cells: potential application in cell-based gene therapy. Rejuvenation Research, 11(2), 379–386.

    Article  PubMed  CAS  Google Scholar 

  45. Kim, J., Kang, H. M., Kim, H., et al. (2007). Ex vivo characteristics of human amniotic membrane-derived stem cells. Cloning and Stem Cells, 9(4), 581–594.

    Article  PubMed  CAS  Google Scholar 

  46. Kita, K., Gauglitz, G. G., Phan, T. T., Herndon, D. N., & Jeschke, M. G. (2010). Isolation and characterization of mesenchymal stem cells from the sub-amniotic human umbilical cord lining membrane. Stem Cells and Development, 19(4), 491–502.

    Article  PubMed  CAS  Google Scholar 

  47. Kong, X. Y., Cai, Z., Pan, L., et al. (2008). Transplantation of human amniotic cells exerts neuroprotection in MPTP-induced Parkinson disease mice. Brain Research, 1205, 108–115.

    Article  PubMed  CAS  Google Scholar 

  48. Kotoula, V., Papamichos, S. I., & Lambropoulos, A. F. (2008). Revisiting OCT4 expression in peripheral blood mononuclear cells. Stem Cells, 26(1), 290–291.

    Article  PubMed  CAS  Google Scholar 

  49. Kucia, M., Machalinski, B., & Ratajczak, M. Z. (2006). The developmental deposition of epiblast/germ cell-line derived cells in various organs as a hypothetical explanation of stem cell plasticity? Acta Neurobiol Exp (Wars), 66(4), 331–341.

    Google Scholar 

  50. La Rocca, G., Anzalone, R., Corrao, S., et al. (2009). Isolation and characterization of OCT- 4+/HLA-G + mesenchymal stem cells from human umbilical cord matrix: differentiation potential and detection of new markers. Histochemistry and Cell Biology, 131(2), 267–282.

    Article  PubMed  CAS  Google Scholar 

  51. Lai, R. C., Arslan, F., Tan, S. S., et al. (2010). Derivation and characterization of human fetal MSCs: an alternative cell source for large-scale production of cardioprotective microparticles. Journal of Molecular and Cellular Cardiology, 48(6), 1215–1224.

    Article  PubMed  CAS  Google Scholar 

  52. Le Blanc, K., Gotherstrom, C., Ringden, O., et al. (2005). Fetal mesenchymal stem-cell engraftment in bone after in utero transplantation in a patient with severe osteogenesis imperfecta. Transplantation, 79(11), 1607–1614.

    Article  PubMed  Google Scholar 

  53. Lee, J., Kim, H. K., Rho, J. Y., Han, Y. M., & Kim, J. (2006). The human OCT- 4 isoforms differ in their ability to confer self-renewal. Journal of Biological Chemistry, 281(44), 33554–33565.

    Article  PubMed  CAS  Google Scholar 

  54. Lee, O. K., Kuo, T. K., Chen, W. M., Lee, K. D., Hsieh, S. L., & Chen, T. H. (2004). Isolation of multipotent mesenchymal stem cells from umbilical cord blood. Blood, 103(5), 1669–1675.

    Article  PubMed  CAS  Google Scholar 

  55. Lian, Q., Lye, E., Suan Yeo, K., et al. (2007). Derivation of clinically compliant MSCs from CD105+, CD24- differentiated human ESCs. Stem Cells, 25(2), 425–436.

    Article  PubMed  CAS  Google Scholar 

  56. Liedtke, S., Stephan, M., & Kogler, G. (2008). Oct4 expression revisited: potential pitfalls for data misinterpretation in stem cell research. Biological Chemistry, 389(7), 845–850.

    Article  PubMed  CAS  Google Scholar 

  57. Lu, L. L., Liu, Y. J., Yang, S. G., et al. (2006). Isolation and characterization of human umbilical cord mesenchymal stem cells with hematopoiesis-supportive function and other potentials. Haematologica, 91(8), 1017–1026.

    PubMed  CAS  Google Scholar 

  58. Macias, M. I., Grande, J., Moreno, A., Dominguez, I., Bornstein, R., Flores, A. I. (2010). Isolation and characterization of true mesenchymal stem cells derived from human term decidua capable of multilineage differentiation into all 3 embryonic layers. Am J Obstet Gynecol, 203(5), 495 e499–495 e423.

    Google Scholar 

  59. Marcus, A. J., & Woodbury, D. (2008). Fetal stem cells from extra-embryonic tissues: do not discard. Journal of Cellular and Molecular Medicine, 12(3), 730–742.

    Article  PubMed  CAS  Google Scholar 

  60. Mareschi, K., Rustichelli, D., Comunanza, V., et al. (2009). Multipotent mesenchymal stem cells from amniotic fluid originate neural precursors with functional voltage-gated sodium channels. Cytotherapy, 11(5), 534–547.

    Article  PubMed  CAS  Google Scholar 

  61. Miao, Z., Jin, J., Chen, L., et al. (2006). Isolation of mesenchymal stem cells from human placenta: comparison with human bone marrow mesenchymal stem cells. Cell Biology International, 30(9), 681–687.

    Article  PubMed  CAS  Google Scholar 

  62. Mihu, C. M., Rus Ciuca, D., Soritau, O., Susman, S., & Mihu, D. (2009). Isolation and characterization of mesenchymal stem cells from the amniotic membrane. Romanian Journal of Morphology and Embryology, 50(1), 73–77.

    PubMed  Google Scholar 

  63. Miki, T., Mitamura, K., Ross, M. A., Stolz, D. B., & Strom, S. C. (2007). Identification of stem cell marker-positive cells by immunofluorescence in term human amnion. Journal of Reproductive Immunology, 75(2), 91–96.

    Article  PubMed  CAS  Google Scholar 

  64. Mirebella, T., Poggi, A., Scaranari, M., et al. (2011). Recruitment of host’s progenitor cells to sites of human amniotic fluid stem cells implantation. Biomaterials, 32(18), 4218–4227.

    Article  CAS  Google Scholar 

  65. Montemurro, T., Andriolo, G., Montelatici, E., et al. (2011). Differentiation and migration properties of human foetal umbilical cord perivascular cells: potential for lung repair. Journal of Cellular and Molecular Medicine, 15(4), 796–808.

    Article  PubMed  CAS  Google Scholar 

  66. Moon, J. H., Lee, J. R., Jee, B. C., et al. (2008). Successful vitrification of human amnion-derived mesenchymal stem cells. Human Reproduction, 23(8), 1760–1770.

    Article  PubMed  Google Scholar 

  67. Nichols, J., Zevnik, B., Anastassiadis, K., et al. (1998). Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4. Cell, 95(3), 379–391.

    Article  PubMed  CAS  Google Scholar 

  68. Niwa, H., Miyazaki, J., & Smith, A. G. (2000). Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells. Nature Genetics, 24(4), 372–376.

    Article  PubMed  CAS  Google Scholar 

  69. Pacini, S., Carnicelli, V., Trombi, L., et al. (2010). Constitutive expression of pluripotency-associated genes in mesodermal progenitor cells (MPCs). PLoS One, 5(3), e9861.

    Article  PubMed  CAS  Google Scholar 

  70. Pain, D., Chirn, G. W., Strassel, C., & Kemp, D. M. (2005). Multiple retropseudogenes from pluripotent cell-specific gene expression indicates a potential signature for novel gene identification. Journal of Biological Chemistry, 280(8), 6265–6268.

    Article  PubMed  CAS  Google Scholar 

  71. Panagopoulos, I., Moller, E., Collin, A., & Mertens, F. (2008). The POU5F1P1 pseudogene encodes a putative protein similar to POU5F1 isoform 1. Oncology Reports, 20(5), 1029–1033.

    PubMed  CAS  Google Scholar 

  72. Parolini, O., Alviano, F., Bagnara, G. P., et al. (2008). Concise review: isolation and characterization of cells from human term placenta: outcome of the first international Workshop on Placenta Derived Stem Cells. Stem Cells, 26(2), 300–311.

    Article  PubMed  Google Scholar 

  73. Pesce, M., Gross, M. K., & Scholer, H. R. (1998). In line with our ancestors: OCT- 4 and the mammalian germ. Bioessays, 20(9), 722–732.

    Article  PubMed  CAS  Google Scholar 

  74. Poloni, A., Maurizi, G., Babini, L., et al. Human mesenchymal stem cells from chorionic villi and amniotic fluid are not susceptible to transformation after extensive in vitro expansion. Cell Transplant, 20(5), 643–654.

  75. Poloni, A., Rosini, V., Mondini, E., et al. (2008). Characterization and expansion of mesenchymal progenitor cells from first-trimester chorionic villi of human placenta. Cytotherapy, 10(7), 690–697.

    Article  PubMed  CAS  Google Scholar 

  76. Portmann-Lanz, C. B., Schoeberlein, A., Huber, A., et al. (2006). Placental mesenchymal stem cells as potential autologous graft for pre- and perinatal neuroregeneration. American Journal of Obstetrics and Gynecology, 194(3), 664–673.

    Article  PubMed  CAS  Google Scholar 

  77. Prusa, A. R., Marton, E., Rosner, M., Bernaschek, G., & Hengstschlager, M. (2003). OCT- 4-expressing cells in human amniotic fluid: a new source for stem cell research? Human Reproduction, 18(7), 1489–1493.

    Article  PubMed  Google Scholar 

  78. Qian, H., Zhang, X., Xu, W., et al. (2010). Lentivirus-modified human umbilical cord mesenchymal stem cells maintain their pluripotency. Biotechnology and Applied Biochemistry, 55(1), 53–62.

    Article  PubMed  CAS  Google Scholar 

  79. Ramkisoensing, A. A., Pijnappels, D. A., Askar, S. F., et al. (2011). Human Embryonic and Fetal Mesenchymal Stem Cells Differentiate toward Three Different Cardiac Lineages in Contrast to Their Adult Counterparts. PLoS One, 6(9), e24164.

    Article  PubMed  CAS  Google Scholar 

  80. Ratajczak, M. Z., Machalinski, B., Wojakowski, W., Ratajczak, J., & Kucia, M. (2007). A hypothesis for an embryonic origin of pluripotent OCT- 4(+) stem cells in adult bone marrow and other tissues. Leukemia, 21(5), 860–867.

    PubMed  CAS  Google Scholar 

  81. Riekstina, U., Cakstina, I., Parfejevs, V., et al. (2009). Embryonic stem cell marker expression pattern in human mesenchymal stem cells derived from bone marrow, adipose tissue, heart and dermis. Stem Cell Reviews, 5(4), 378–386.

    Article  PubMed  CAS  Google Scholar 

  82. Roelen, D. L., van der Mast, B. J., In’t Anker, P. S., et al. (2009). Differential immunomodulatory effects of fetal versus maternal multipotent stromal cells. Human Immunology, 70(1), 16–23.

    Article  PubMed  CAS  Google Scholar 

  83. Romanov, Y. A., Svintsitskaya, V. A., & Smirnov, V. N. (2003). Searching for alternative sources of postnatal human mesenchymal stem cells: candidate MSC-like cells from umbilical cord. Stem Cells, 21(1), 105–110.

    Article  PubMed  Google Scholar 

  84. Roubelakis, M. G., Pappa, K. I., Bitsika, V., et al. (2007). Molecular and proteomic characterization of human mesenchymal stem cells derived from amniotic fluid: comparison to bone marrow mesenchymal stem cells. Stem Cells and Development, 16(6), 931–952.

    Article  PubMed  CAS  Google Scholar 

  85. Sarugaser, R., Lickorish, D., Baksh, D., Hosseini, M. M., & Davies, J. E. (2005). Human umbilical cord perivascular (HUCPV) cells: a source of mesenchymal progenitors. Stem Cells, 23(2), 220–229.

    Article  PubMed  Google Scholar 

  86. Secco, M., Zucconi, E., Vieira, N. M., et al. (2008). Mesenchymal stem cells from umbilical cord: do not discard the cord! Neuromuscular Disorders, 18(1), 17–18.

    Article  PubMed  Google Scholar 

  87. Semenov, O. V., Koestenbauer, S., Riegel, M., et al. (2010). Multipotent mesenchymal stem cells from human placenta: critical parameters for isolation and maintenance of stemness after isolation. Am J Obstet Gynecol, 202(2), 193 e191–193 e113.

    Google Scholar 

  88. Soncini, M., Vertua, E., Gibelli, L., et al. (2007). Isolation and characterization of mesenchymal cells from human fetal membranes. Journal of Tissue Engineering and Regenerative Medicine, 1(4), 296–305.

    Article  PubMed  CAS  Google Scholar 

  89. Sung, H. J., Hong, S. C., Yoo, J. H., et al. (2010). Stemness evaluation of mesenchymal stem cells from placentas according to developmental stage: comparison to those from adult bone marrow. Journal of Korean Medical Science, 25(10), 1418–1426.

    Article  PubMed  CAS  Google Scholar 

  90. Suo, G., Han, J., Wang, X., Zhang, J., Zhao, Y., & Dai, J. (2005). Oct4 pseudogenes are transcribed in cancers. Biochemical and Biophysical Research Communications, 337(4), 1047–1051.

    Article  PubMed  CAS  Google Scholar 

  91. Takeda, J., Seino, S., & Bell, G. I. (1992). Human Oct3 gene family: cDNA sequences, alternative splicing, gene organization, chromosomal location, and expression at low levels in adult tissues. Nucleic Acids Research, 20(17), 4613–4620.

    Article  PubMed  CAS  Google Scholar 

  92. Tang, C., Lee, A. S., Volkmer, J. P., et al. An antibody against SSEA-5 glycan on human pluripotent stem cells enables removal of teratoma-forming cells. Nat Biotechnol.

  93. Thomson, J. A., Itskovitz-Eldor, J., Shapiro, S. S., et al. (1998). Embryonic stem cell lines derived from human blastocysts. Science, 282(5391), 1145–1147.

    Article  PubMed  CAS  Google Scholar 

  94. Tong, C. K., Vellasamy, S., Tan, B. C., et al. (2011). Generation of mesenchymal stem cell from human umbilical cord tissue using a combination enzymatic and mechanical disassociation method. Cell Biology International, 35(3), 221–226.

    Article  PubMed  CAS  Google Scholar 

  95. Troyer, D. L., & Weiss, M. L. (2008). Wharton’s jelly-derived cells are a primitive stromal cell population. Stem Cells, 26(3), 591–599.

    Article  PubMed  Google Scholar 

  96. Trubiani, O., Zalzal, S. F., Paganelli, R., et al. (2010). Expression profile of the embryonic markers nanog, OCT- 4, SSEA-1, SSEA-4, and frizzled-9 receptor in human periodontal ligament mesenchymal stem cells. Journal of Cellular Physiology, 225(1), 123–131.

    Article  PubMed  CAS  Google Scholar 

  97. Tsai, M. S., Lee, J. L., Chang, Y. J., & Hwang, S. M. (2004). Isolation of human multipotent mesenchymal stem cells from second-trimester amniotic fluid using a novel two-stage culture protocol. Human Reproduction, 19(6), 1450–1456.

    Article  PubMed  Google Scholar 

  98. Vanleene, M., Saldanha, Z., Cloyd, K. L., et al. (2011). Transplantation of human fetal blood stem cells in the osteogenesis imperfecta mouse leads to improvement in multiscale tissue properties. Blood, 117(3), 1053–1060.

    Article  PubMed  CAS  Google Scholar 

  99. Wang, H. S., Hung, S. C., Peng, S. T., et al. (2004). Mesenchymal stem cells in the Wharton’s jelly of the human umbilical cord. Stem Cells, 22(7), 1330–1337.

    Article  PubMed  Google Scholar 

  100. Weiss, M. L., Medicetty, S., Bledsoe, A. R., et al. (2006). Human umbilical cord matrix stem cells: preliminary characterization and effect of transplantation in a rodent model of Parkinson’s disease. Stem Cells, 24(3), 781–792.

    Article  PubMed  CAS  Google Scholar 

  101. Wolbank, S., Peterbauer, A., Fahrner, M., et al. (2007). Dose-dependent immunomodulatory effect of human stem cells from amniotic membrane: a comparison with human mesenchymal stem cells from adipose tissue. Tissue Engineering, 13(6), 1173–1183.

    Article  PubMed  CAS  Google Scholar 

  102. Yen, B. L., Huang, H. I., Chien, C. C., et al. (2005). Isolation of multipotent cells from human term placenta. Stem Cells, 23(1), 3–9.

    Article  PubMed  CAS  Google Scholar 

  103. You, Q., Tong, X., Guan, Y., et al. (2009). The biological characteristics of human third trimester amniotic fluid stem cells. The Journal of International Medical Research, 37(1), 105–112.

    Article  PubMed  CAS  Google Scholar 

  104. Zaibak, F., Bello, P., Kozlovski, J., et al. (2009). Unrestricted somatic stem cells from human umbilical cord blood grow in serum-free medium as spheres. BMC Biotechnol, 9(101).

  105. Zangrossi, S., Marabese, M., Broggini, M., et al. (2007). OCT- 4 expression in adult human differentiated cells challenges its role as a pure stem cell marker. Stem Cells, 25(7), 1675–1680.

    Article  PubMed  CAS  Google Scholar 

  106. Zhang, P., Baxter, J., Vinod, K., Tulenko, T. N., & Di Muzio, P. J. (2009). Endothelial differentiation of amniotic fluid-derived stem cells: synergism of biochemical and shear force stimuli. Stem Cells and Development, 18(9), 1299–1308.

    Article  PubMed  CAS  Google Scholar 

  107. Zhang, X., Hirai, M., Cantero, S., et al. (2011). Isolation and characterization of mesenchymal stem cells from human umbilical cord blood: reevaluation of critical factors for successful isolation and high ability to proliferate and differentiate to chondrocytes as compared to mesenchymal stem cells from bone marrow and adipose tissue. Journal of Cellular Biochemistry, 112(4), 1206–1218.

    Article  PubMed  CAS  Google Scholar 

  108. Zhang, Y., Li, C. D., Jiang, X. X., Li, H. L., Tang, P. H., & Mao, N. (2004). Comparison of mesenchymal stem cells from human placenta and bone marrow. Chinese Medical Journal, 117(6), 882–887.

    PubMed  CAS  Google Scholar 

  109. Zhang, Z. Y., Teoh, S. H., Chong, M. S., et al. (2010). Neo-vascularization and bone formation mediated by fetal mesenchymal stem cell tissue-engineered bone grafts in critical-size femoral defects. Biomaterials, 31(4), 608–620.

    Article  PubMed  CAS  Google Scholar 

  110. Zhang, Z. Y., Teoh, S. H., Chong, M. S., et al. (2009). Superior osteogenic capacity for bone tissue engineering of fetal compared with perinatal and adult mesenchymal stem cells. Stem Cells, 27(1), 126–137.

    Article  PubMed  CAS  Google Scholar 

  111. Zhao, P., Ise, H., Hongo, M., Ota, M., Konishi, I., & Nikaido, T. (2005). Human amniotic mesenchymal cells have some characteristics of cardiomyocytes. Transplantation, 79(5), 528–535.

    Article  PubMed  Google Scholar 

  112. Zhao, Y., Wang, H., & Mazzone, T. (2006). Identification of stem cells from human umbilical cord blood with embryonic and hematopoietic characteristics. Experimental Cell Research, 312(13), 2454–2464.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgement

Work on fetal stem cells in our groups is funded (i) in Australia by the National Health & Medical Research Council, the Australian Research Council, and the Australian Stem Cell Centre (ii) in the UK by the Genesis Research Trust and Research Councils UK and (iii) in Singapore by the Bio-Medical Research Council and National Medical Research Council.

Competing interests

The authors declare no potential conflicts of interest.

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Authors and Affiliations

  1. UQ Centre for Clinical Research, University of Queensland, Herston campus, Brisbane, 4029, Australia

    Jennifer M. Ryan, Allison R. Pettit, Jerry K. Y. Chan & Nicholas M. Fisk

  2. Fetal Stem Cell Therapy Group, Institute of Reproductive & Developmental Biology, Imperial College, London, W12 ONN, United Kingdom

    Pascale V. Guillot

  3. Experimental Fetal Medicine Group, Department of Obstetrics & Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    Jerry K. Y. Chan & Nicholas M. Fisk

  4. Department of Reproductive Medicine, KK Women’s and Children’s Hospital, Singapore, Singapore

    Jerry K. Y. Chan

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  1. Jennifer M. Ryan
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  2. Allison R. Pettit
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  3. Pascale V. Guillot
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  4. Jerry K. Y. Chan
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Correspondence to Jennifer M. Ryan.

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Ryan, J.M., Pettit, A.R., Guillot, P.V. et al. Unravelling the Pluripotency Paradox in Fetal and Placental Mesenchymal Stem Cells: Oct-4 Expression and the Case of the Emperor’s New Clothes. Stem Cell Rev and Rep 9, 408–421 (2013). https://doi.org/10.1007/s12015-011-9336-5

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