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In toto differentiation of human amniotic membrane towards the Schwann cell lineage

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Abstract

Human amniotic membrane (hAM) is a tissue containing cells with proven stem cell properties. In its decellularized form it has been successfully applied as nerve conduit biomaterial to improve peripheral nerve regeneration in injury models. We hypothesize that viable hAM without prior cell isolation can be differentiated towards the Schwann cell lineage to generate a possible alternative to commonly applied tissue engineering materials for nerve regeneration. For in vitro Schwann cell differentiation, biopsies of hAM of 8 mm diameter were incubated with a sequential order of neuronal induction and growth factors for 21 days and characterized for cellular viability and the typical glial markers glial fibrillary acidic protein (GFAP), S100β, p75 and neurotrophic tyrosine kinase receptor (NTRK) using immunohistology. The secretion of the neurotrophic factors brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF) was quantified by ELISA. The hAM maintained high viability, especially under differentiation conditions (90.2 % ± 41.6 day 14; 80.0 % ± 44.5 day 21 compared to day 0). Both, BDNF and GDNF secretion was up-regulated upon differentiation. The fresh membrane stained positive for GFAP and p75 and NTRK, which was strongly increased after culture in differentiation conditions. Especially the epithelial layer within the membrane exhibited a change in morphology upon differentiation forming a multi-layered epithelium with intense accumulations of the marker proteins. However, S100β was expressed at equal levels and equal distribution in fresh and cultured hAM conditions. Viable hAM may be a promising alternative to present formulations used for peripheral nerve regeneration.

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References

  • Adinolfi M, Akle CA, McColl I, Fensom AH, Tansley L, Connolly P, Hsi BL, Faulk WP, Travers P, Bodmer WF (1982) Expression of HLA antigens, beta 2-microglobulin and enzymes by human amniotic epithelial cells. Nature 295:325–327

    Article  CAS  PubMed  Google Scholar 

  • Akle CA, Adinolfi M, Welsh KI, Leibowitz S, McColl I (1981) Immunogenicity of human amniotic epithelial cells after transplantation into volunteers. Lancet 2:1003–1005

    Article  CAS  PubMed  Google Scholar 

  • Bailo M, Soncini M, Vertua E, Signoroni PB, Sanzone S, Lombardi G, Arienti D, Calamani F, Zatti D, Paul P, Albertini A, Zorzi F, Cavagnini A, Candotti F, Wengler GS, Parolini O (2004) Engraftment potential of human amnion and chorion cells derived from term placenta. Transplantation 78:1439–1448

    Article  PubMed  Google Scholar 

  • Caddick J, Kingham PJ, Gardiner NJ, Wiberg M, Terenghi G (2006) Phenotypic and functional characteristics of mesenchymal stem cells differentiated along a Schwann cell lineage. Glia 54:840–849

    Article  PubMed  Google Scholar 

  • Cargnoni A, Gibelli L, Tosini A, Signoroni PB, Nassuato C, Arienti D, Lombardi G, Albertini A, Wengler GS, Parolini O (2009) Transplantation of allogeneic and xenogeneic placenta-derived cells reduces bleomycin-induced lung fibrosis. Cell Transpl 18:405–422

    Article  Google Scholar 

  • Chernousov MA, Yu WM, Chen ZL, Carey DJ, Strickland S (2008) Regulation of Schwann cell function by the extracellular matrix. Glia 56:1498–1507

    Article  PubMed  Google Scholar 

  • Davis GE, Blaker SN, Engvall E, Varon S, Manthorpe M, Gage FH (1987) Human amnion membrane serves as a substratum for growing axons in vitro and in vivo. Science 236:1106–1109

    Article  CAS  PubMed  Google Scholar 

  • di Summa PG, Kalbermatten DF, Raffoul W, Terenghi G, Kingham PJ (2013) Extracellular matrix molecules enhance the neurotrophic effect of Schwann cell-like differentiated adipose-derived stem cells and increase cell survival under stress conditions. Tissue Eng Part A 19:368–379

    Article  PubMed Central  PubMed  Google Scholar 

  • Hennerbichler S, Reichl B, Pleiner D, Gabriel C, Eibl J, Redl H (2007) The influence of various storage conditions on cell viability in amniotic membrane. Cell Tissue Bank 8:1–8

    Article  CAS  PubMed  Google Scholar 

  • Hubert T, Grimal S, Carroll P, Fichard-Carroll A (2009) Collagens in the developing and diseased nervous system. Cell Mol Life Sci 66:1223–1238

    Article  CAS  PubMed  Google Scholar 

  • Insausti CL, Blanquer M, Bleda P, Iniesta P, Majado MJ, Castellanos G, Moraleda JM (2010) The amniotic membrane as a source of stem cells. Histol Histopathol 25:91–98

    CAS  PubMed  Google Scholar 

  • Jiang L, Zhu JK, Liu XL, Xiang P, Hu J, Yu WH (2008) Differentiation of rat adipose tissue-derived stem cells into Schwann-like cells in vitro. Neuroreport 19:1015–1019

    Article  PubMed  Google Scholar 

  • Kakishita K, Nakao N, Sakuragawa N, Itakura T (2003) Implantation of human amniotic epithelial cells prevents the degeneration of nigral dopamine neurons in rats with 6-hydroxydopamine lesions. Brain Res 980:48–56

    Article  CAS  PubMed  Google Scholar 

  • Keilhoff G, Goihl A, Stang F, Wolf G, Fansa H (2006a) Peripheral nerve tissue engineering: autologous Schwann cells versus transdifferentiated mesenchymal stem cells. Tissue Eng 12:1451–1465

    Article  CAS  PubMed  Google Scholar 

  • Keilhoff G, Stang F, Goihl A, Wolf G, Fansa H (2006b) Transdifferentiated mesenchymal stem cells as alternative therapy in supporting nerve regeneration and myelination. Cell Mol Neurobiol 26:1235–1252

    Article  PubMed  Google Scholar 

  • Kingham PJ, Kalbermatten DF, Mahay D, Armstrong SJ, Wiberg M, Terenghi G (2007) Adipose-derived stem cells differentiate into a Schwann cell phenotype and promote neurite outgrowth in vitro. Exp Neurol 207:267–274

    Article  CAS  PubMed  Google Scholar 

  • Kronsteiner B, Peterbauer-Scherb A, Grillari-Voglauer R, Redl H, Gabriel C, van Griensven M, Wolbank S (2011a) Human mesenchymal stem cells and renal tubular epithelial cells differentially influence monocyte-derived dendritic cell differentiation and maturation. Cell Immunol 267:30–38

    Article  CAS  PubMed  Google Scholar 

  • Kronsteiner B, Wolbank S, Peterbauer A, Hackl C, Redl H, van Griensven M, Gabriel C (2011b) Human mesenchymal stem cells from adipose tissue and amnion influence T-cells depending on stimulation method and presence of other immune cells. Stem Cells Dev 20:2115–2126

    Article  CAS  PubMed  Google Scholar 

  • Liang HS, Liang P, Xu Y, Wu JN, Liang T, Xu XP, Liu EZ (2009) Denuded human amniotic membrane seeding bone marrow stromal cells as an effective composite matrix stimulates axonal outgrowth of rat neural cortical cells in vitro. Acta Neurochir (Wien) 151:1113–1120

    Article  Google Scholar 

  • Liang H, Li C, Gao A, Liang P, Shao Y, Lin T, Zhang X (2012) Spinal duraplasty with two novel substitutes restored locomotor function after acute laceration spinal cord injury in rats. J Biomed Mater Res B Appl Biomater 100:2131–2140

    Article  PubMed  Google Scholar 

  • Lindenmair A, Wolbank S, Stadler G, Meinl A, Peterbauer-Scherb A, Eibl J, Polin H, Gabriel C, van Griensven M, Redl H (2010) Osteogenic differentiation of intact human amniotic membrane. Biomaterials 31:8659–8665

    Article  CAS  PubMed  Google Scholar 

  • Mahay D, Terenghi G, Shawcross SG (2008) Schwann cell mediated trophic effects by differentiated mesenchymal stem cells. Exp Cell Res 314:2692–2701

    Article  CAS  PubMed  Google Scholar 

  • Mahmoudi-Rad M, Abolhasani E, Moravvej H, Mahmoudi-Rad N, Mirdamadi Y (2013) Acellular amniotic membrane: an appropriate scaffold for fibroblast proliferation. Clin Exp Dermatol 38:646–651

    Article  CAS  PubMed  Google Scholar 

  • Manuelpillai U, Lourensz D, Vaghjiani V, Tchongue J, Lacey D, Tee JY, Murthi P, Chan J, Hodge A, Sievert W (2012) Human amniotic epithelial cell transplantation induces markers of alternative macrophage activation and reduces established hepatic fibrosis. PLoS ONE 7:e38631

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Miki T, Strom SC (2006) Amnion-derived pluripotent/multipotent stem cells. St Cell Rev 2:133–142

    Article  CAS  Google Scholar 

  • Mligiliche N, Endo K, Okamoto K, Fujimoto E, Ide C (2002) Extracellular matrix of human amnion manufactured into tubes as conduits for peripheral nerve regeneration. J Biomed Mater Res 63:591–600

    Article  CAS  PubMed  Google Scholar 

  • Ndubaku U, de Bellard ME (2008) Glial cells: old cells with new twists. Acta Histochem 110:182–195

    Article  PubMed Central  PubMed  Google Scholar 

  • Park HW, Lim MJ, Jung H, Lee SP, Paik KS, Chang MS (2010) Human mesenchymal stem cell-derived Schwann cell-like cells exhibit neurotrophic effects, via distinct growth factor production, in a model of spinal cord injury. Glia 58:1118–1132

    Article  PubMed  Google Scholar 

  • Parolini O, Alviano F, Bergwerf I, Boraschi D, De BC, De WP, Dominici M, Evangelista M, Falk W, Hennerbichler S, Hess DC, Lanzoni G, Liu B, Marongiu F, McGuckin C, Mohr S, Nolli ML, Ofir R, Ponsaerts P, Romagnoli L, Solomon A, Soncini M, Strom S, Surbek D, Venkatachalam S, Wolbank S, Zeisberger S, Zeitlin A, Zisch A, Borlongan CV (2010) Toward cell therapy using placenta-derived cells: disease mechanisms, cell biology, preclinical studies, and regulatory aspects at the round table. St Cells Dev 19:143–154

    Article  Google Scholar 

  • Peterbauer-Scherb A, Danzer M, Gabriel C, van Griensven M, Redl H, Wolbank S (2012) In vitro adipogenesis of adipose-derived stem cells in 3D fibrin matrix of low component concentration. J Tissue Eng Regen Med 6:434–442

    Article  CAS  PubMed  Google Scholar 

  • Pratama G, Vaghjiani V, Tee JY, Liu YH, Chan J, Tan C, Murthi P, Gargett C, Manuelpillai U (2011) Changes in culture expanded human amniotic epithelial cells: implications for potential therapeutic applications. PLoS ONE 6:e26136

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Riau AK, Beuerman RW, Lim LS, Mehta JS (2010) Preservation, sterilization and de-epithelialization of human amniotic membrane for use in ocular surface reconstruction. Biomaterials 31:216–225

    Article  CAS  PubMed  Google Scholar 

  • Ricci E, Vanosi G, Lindenmair A, Hennerbichler S, Peterbauer-Scherb A, Wolbank S, Cargnoni A, Signoroni PB, Campagnol M, Gabriel C, Redl H, Parolini O (2012) Anti-fibrotic effects of fresh and cryopreserved human amniotic membrane in a rat liver fibrosis model. Cell Tissue Bank

  • Sakuragawa N, Kakinuma K, Kikuchi A, Okano H, Uchida S, Kamo I, Kobayashi M, Yokoyama Y (2004) Human amnion mesenchyme cells express phenotypes of neuroglial progenitor cells. J Neurosci Res 78:208–214

    Article  CAS  PubMed  Google Scholar 

  • Stadler G, Hennerbichler S, Lindenmair A, Peterbauer A, Hofer K, van Griensven M, Gabriel C, Redl H, Wolbank S (2008) Phenotypic shift of human amniotic epithelial cells in culture is associated with reduced osteogenic differentiation in vitro. Cytotherapy 10:743–752

    Article  CAS  PubMed  Google Scholar 

  • Takashima S, Yasuo M, Sanzen N, Sekiguchi K, Okabe M, Yoshida T, Toda A, Nikaido T (2008) Characterization of laminin isoforms in human amnion. Tissue Cell 40:75–81

    Article  CAS  PubMed  Google Scholar 

  • Terenghi G (1999) Peripheral nerve regeneration and neurotrophic factors. J Anat 194(Pt 1):1–14

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Tohill M, Mantovani C, Wiberg M, Terenghi G (2004) Rat bone marrow mesenchymal stem cells express glial markers and stimulate nerve regeneration. Neurosci Lett 362:200–203

    Article  CAS  PubMed  Google Scholar 

  • Tomita K, Madura T, Sakai Y, Yano K, Terenghi G, Hosokawa K (2013) Glial differentiation of human adipose-derived stem cells: implications for cell-based transplantation therapy. Neuroscience 236:55–65

    Article  CAS  PubMed  Google Scholar 

  • Uchida S, Inanaga Y, Kobayashi M, Hurukawa S, Araie M, Sakuragawa N (2000) Neurotrophic function of conditioned medium from human amniotic epithelial cells. J Neurosci Res 62:585–590

    Article  CAS  PubMed  Google Scholar 

  • Uziyel Y, Hall S, Cohen J (2000) Influence of laminin-2 on Schwann cell-axon interactions. Glia 32:109–121

    Article  CAS  PubMed  Google Scholar 

  • Wallquist W, Plantman S, Thams S, Thyboll J, Kortesmaa J, Lannergren J, Domogatskaya A, Ogren SO, Risling M, Hammarberg H, Tryggvason K, Cullheim S (2005) Impeded interaction between Schwann cells and axons in the absence of laminin alpha4. J Neurosci 25:3692–3700

    Article  CAS  PubMed  Google Scholar 

  • Wang J, Ding F, Gu Y, Liu J, Gu X (2009) Bone marrow mesenchymal stem cells promote cell proliferation and neurotrophic function of Schwann cells in vitro and in vivo. Brain Res 1262:7–15

    Article  CAS  PubMed  Google Scholar 

  • Whittle WL, Gibb W, Challis JR (2000) The characterization of human amnion epithelial and mesenchymal cells: the cellular expression, activity and glucocorticoid regulation of prostaglandin output. Placenta 21:394–401

    Article  CAS  PubMed  Google Scholar 

  • Wilshaw SP, Kearney J, Fisher J, Ingham E (2008) Biocompatibility and potential of acellular human amniotic membrane to support the attachment and proliferation of allogeneic cells. Tissue Eng Part A 14:463–472

    Article  CAS  PubMed  Google Scholar 

  • Wolbank S, Hildner F, Redl H, van Griensven M, Gabriel C, Hennerbichler S (2009) Impact of human amniotic membrane preparation on release of angiogenic factors. J Tissue Eng Regen Med 3:651–654

    Article  CAS  PubMed  Google Scholar 

  • Xu Y, Liu L, Li Y, Zhou C, Xiong F, Liu Z, Gu R, Hou X, Zhang C (2008) Myelin-forming ability of Schwann cell-like cells induced from rat adipose-derived stem cells in vitro. Brain Res 1239:49–55

    Article  CAS  PubMed  Google Scholar 

  • Xue H, Zhang XY, Liu JM, Song Y, Li YF, Chen D (2013) Development of a chemically extracted acellular muscle scaffold seeded with amniotic epithelial cells to promote spinal cord repair. J Biomed Mater Res A 101:145–156

    Article  PubMed  Google Scholar 

  • Yan ZJ, Zhang P, Hu YQ, Zhang HT, Hong SQ, Zhou HL, Zhang MY, Xu RX (2013) Neural stem-like cells derived from human amnion tissue are effective in treating traumatic brain injury in rat. Neurochem Res 38:1022–1033

    Article  CAS  PubMed  Google Scholar 

  • Yang S, Xue DD, Wu B, Sun HM, Li XS, Dong F, Li WS, Ji FQ, Zhou DS (2013) Pleiotrophin is involved in the amniotic epithelial cell-induced differentiation of human umbilical cord blood-derived mesenchymal stem cells into dopaminergic neuron-like cells. Neurosci Lett 539:86–91

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We would like to thank Daniela Dopler, Alice Zimmermann and Sidrah Chaudry for their technical assistance and Eva Schwingenschlögl for support with graphic design.

Conflict of interest

We would like to disclose that the co-authors Johann Eibl and Heinz Redl own the patent rights for “Process for differentiating stem cells of the amniotic membrane”.

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Authors and Affiliations

  1. Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Center, Donaueschingenstraße 13, 1200, Vienna, Austria

    Asmita Banerjee, Sylvia Nürnberger, Sabrina Riedl, Christina M. A. P. Schuh, Ara Hacobian, Heinz Redl & Susanne Wolbank

  2. Austrian Cluster for Tissue Regeneration, Vienna, Austria

    Asmita Banerjee, Simone Hennerbichler, Sabrina Riedl, Christina M. A. P. Schuh, Ara Hacobian, Andreas Teuschl, Heinz Redl & Susanne Wolbank

  3. Red Cross Blood Transfusion Service for Upper Austria, Krankenhausstr., 4017, Linz, Austria

    Simone Hennerbichler

  4. Bio-Products and Bio-Engineering AG, Schottenring 10, 1010, Vienna, Austria

    Johann Eibl

  5. City of Vienna Competence Team Tissue Engineering Bioreactors, University of Applied Science Technikum Wien, Höchstädtplatz 6, 1200, Vienna, Austria

    Andreas Teuschl

  6. Department of Biochemical Engineering, University of Applied Science Technikum Wien, Höchstädtplatz 6, 1200, Vienna, Austria

    Andreas Teuschl

  7. Department of Traumatology, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria

    Sylvia Nürnberger

  8. Bernhard Gottlieb University Clinic of Dentistry, Sensengasse 2a, 1090, Vienna, Austria

    Sylvia Nürnberger

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  1. Asmita Banerjee
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  2. Sylvia Nürnberger
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  3. Simone Hennerbichler
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  4. Sabrina Riedl
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  5. Christina M. A. P. Schuh
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  6. Ara Hacobian
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  7. Andreas Teuschl
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  8. Johann Eibl
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  9. Heinz Redl
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  10. Susanne Wolbank
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Correspondence to Simone Hennerbichler.

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Banerjee, A., Nürnberger, S., Hennerbichler, S. et al. In toto differentiation of human amniotic membrane towards the Schwann cell lineage. Cell Tissue Bank 15, 227–239 (2014). https://doi.org/10.1007/s10561-013-9401-1

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  • DOI: https://doi.org/10.1007/s10561-013-9401-1

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