Skip to main content

Advertisement

Log in

Effect of Leukemia Inhibitory Factor on the Myelinogenic Ability of Schwann-Like Cells Induced from Human Adipose-Derived Stem Cells

  • Original Research
  • Published:
Cellular and Molecular Neurobiology Aims and scope Submit manuscript

Abstract

The Schwann cells (SCs) may be obtain from nerve biopsies for autologous transplantation. However, it is difficult to obtain sufficient amount of SCs for clinical applications. Human adipose-derived stem cells (ADSCs) can be induced to differentiate into Schwann-like cells (S-like cells) and used for autologous transplantation. However, effect of leukemia inhibitory factor (LIF) on the myelinogenic ability of SC-like cells induced from human ADSC is not investigated yet. The aim of this study was to evaluate of the effect of exogenous LIF on myelinogenic potential of differentiated cells in vitro. ADSCs were harvested from human fat tissue and characterized using flow cytometry. Human ADSCs were treated for sphere formation and LIF was added to terminal differentiation medium. GFAP/S100β and MBP markers were used to confirm differentiation of human ADSCs, and myelinogenic ability of SC-like cells, respectively, using both immunostaining and real-time RT-PCR analysis. The analysis for GFAP+/S100β+ revealed that LIF can increase both differentiated cells rates and the percentage of myelinating SC-like cells (p < 0.05). Our data showed that SC-like cells induced from human ADSCs were able to generate myelin when exposed to LIF and these cells could be a potential source for the treatment of peripheral and central axonal injuries.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Ahmadi N, Razavi S, Kazemi M, Oryan S (2011) Stability of neural differentiation in human adipose derived stem cells by two induction protocols. Tissue Cell 44:87–94

    Article  PubMed  Google Scholar 

  • Azari MF, Profyris C, Karnezis T, Bernard CC, Small DH, Cheema SS, Ozturk E, Hatzinisiriou I, Petratos S (2006) Leukemia inhibitory factor arrests oligodendrocyte death and demyelination in spinal cord injury. J Neuropathol Exp Neurol 65:914–929

    Article  PubMed  CAS  Google Scholar 

  • Barres BA, Schmid R, Sendnter M, Raff MC (1993) Multiple extracellular signals are required for long-term oligodendrocyte survival. Development 118:283–295

    PubMed  CAS  Google Scholar 

  • Black IB, Woodbury D (2000) Adult rat and human bone marrow stromal cells differentiate into neurons. J Neurosci Res 61:364–370

    Article  PubMed  Google Scholar 

  • Bunge RP (1993) Expanding roles for the Schwann cell: ensheathment, myelination, trophism and regeneration. Curr Opin Neurobiol 3:805–809

    Article  PubMed  CAS  Google Scholar 

  • Bunge RP (1994) The role of the Schwann cell in trophic support and regeneration. J Neurol 242:19–21

    Article  Google Scholar 

  • Butzkueven H, Zhang JG, Soilu-Hanninen M, Hochrein H, Chionh F, Shipham KA, Emery B, Turnley AM, Petratos S, Ernst M, Bartlett PF, Kilpatrick TJ (2002) LIF receptor signaling limits immune mediated demyelination by enhancing oligodendrocyte survival. Nat Med 8:613–619

    Article  PubMed  CAS  Google Scholar 

  • Cheema SS, Richards LJ, Murphy M, Bartlett PF (1994) Leukemia inhibitory factor rescues motoneurones from axotomy induced cell death. Neuroreport 5:989–992

    Article  PubMed  CAS  Google Scholar 

  • Chi GF, Kim MR, Kim DW, Jiang MH, Son Y (2010) Schwann cells differentiated from spheroid-forming cells of rat subcutaneous fat tissue myelinate axons in the spinal cord injury. Exp Neurol 222:304–317

    Article  PubMed  CAS  Google Scholar 

  • Chu G (2003) Embryonic stem-cell research and the moral status of embryos. Intern Med J 33:530–531

    Article  PubMed  CAS  Google Scholar 

  • di Summa PG, Kalbermatten DF, Pralong E, Raffoul W, Kingham PJ, Terenghi G (2011) Long-term in vivo regeneration of peripheral nerves through bioengineered nerve grafts. Neuroscience 181:278–291

    Article  PubMed  Google Scholar 

  • Dowsing BJ, Morrison WA, Nicola NA, Starkey GP, Bucci T, Kilpatrick TJ (1999) Leukemia inhibitory factor is an autocrine survival factor for Schwann cells. J Neurochem 73:96–104

    Article  PubMed  CAS  Google Scholar 

  • Esmaeili A, Zaker SR (2011) Differential expression of glycine receptor subunit messenger RNA in the rat following spinal cord injury. Spinal cord 49:280–284

    Article  PubMed  CAS  Google Scholar 

  • Hall SM (1978) The Schwann cell: a reappraisal of its role in the peripheral nervous system. Neuropathol Appl Neurobiol 4:165–176

    Article  PubMed  CAS  Google Scholar 

  • Hilton DJ, Gough NM (1991) Leukemia inhibitory factor: a biological perspective. J Cell Biochem 46:21–26

    Article  PubMed  CAS  Google Scholar 

  • Ishibashi T, Dakin KA, Stevens B, Lee PR, Kozlov SV, Stewart CL, Fields RD (2006) Astrocytes promote myelinationin response to electrical impulses. Neuron 49:823–832

    Article  PubMed  CAS  Google Scholar 

  • Kaewkhaw R, Scutt AM, Haycock JW (2011) Anatomical site influences the differentiation of adipose-derived stem cells for Schwann-cell phenotype and function. Glia 59:734–749

    Article  PubMed  Google Scholar 

  • Kalbermatten DF, Schaakxs D, Kingham PJ, Wiberg M (2011) Neurotrophic activity of human adipose stem cells isolated from deep and superficial layers of abdominal fat. Cell Tissue Res 344:251–260

    Article  PubMed  CAS  Google Scholar 

  • Kang SK, Lee DH, Bae YC, Kim HK, Baik SY, Jung JS (2003) Improvement of neurological de3 cits by intracerebral transplant of human adipose-derived stem cells after ischemia in rats. Exp Neurol 83:355–366

    Article  Google Scholar 

  • Kang SK, Shin MJ, Jung JS, Kim YG, Kim CH (2006) Autologous adipose tissue-derived stromal cells for treatment of spinal cord injury. Stem Cells Dev 15:583–594

    Article  PubMed  CAS  Google Scholar 

  • Keilhoff G, Goihl A, Langnäse K, Fansa H, Wolf G (2006) Transdifferentiation of mesenchymal stem cells into Schwann cell-like myelinating cells. Eur J Cell Biol 85:11–24

    Article  PubMed  CAS  Google Scholar 

  • Kern S, Eichler H, Stoeve J, Klüter H, Bieback K (2006) Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood or adipose tissue. Stem Cells 24:1294–1301

    Article  PubMed  CAS  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  PubMed  CAS  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  PubMed  CAS  Google Scholar 

  • Mayer M, Bhakoo K, Noble M (1994) Ciliary neurotrophic factor and leukemia inhibitory factor promote the generation, maturation and survival of oligodendrocytes in vitro. Development 120:143–153

    PubMed  CAS  Google Scholar 

  • Metcalf D (2003) The unsolved enigmas of leukemia inhibitory factor. Stem Cells 21:5–14

    Article  PubMed  CAS  Google Scholar 

  • Mimura T, Dezawa M, Kanno H, Sawada H, Yamamoto I (2004) Peripheral nerve regeneration by transplantation of bone marrow stromal cell-derived Schwann cells in adult rats. J Neurosurg 101:806–812

    Article  PubMed  Google Scholar 

  • Mosahebi A, Woodward B, Wiberg M, Martin R, Terenghi G (2001) Retroviral labeling of Schwann cells: in vitro characterization and in vivo transplantation to improve peripheral nerve regeneration. Glia 34:8–17

    Article  PubMed  CAS  Google Scholar 

  • Murphy M, Reid K, Brown MA, Bartlett PF (1993) Involvement of leukemia inhibitory factor and nerve growth factor in the development of dorsal root ganglion neurones. Development 117:1173–1182

    PubMed  CAS  Google Scholar 

  • Nichols CM, Brenner MJ, Fox IK, Tung TH, Hunter DA, Rickman SR, Mackinnon SE (2004) Effects of motor versus sensory nerve grafts on peripheral nerve regeneration. Exp Neurol 190:347–355

    Article  PubMed  Google Scholar 

  • Panseri S, Cunha C, Lowery J, Del Carro U, Taraballi F, Amadio S, Vescovi A, Gelain F (2008) Electrospun micro- and nanofiber tubes for functional nervous regeneration in sciatic nerve transaction. BMC Biotechnol 8:39

    Article  PubMed  Google Scholar 

  • Park SK, Solomon D, Vartanian T (2001) Growth factor control of CNS myelination. Dev Neurosci 23:327–337

    Article  PubMed  CAS  Google Scholar 

  • Razavi S, Ahmadi N, Kazemi M, Mardani M, Esfandiari E (2012) Efficient transdifferentiation of human adipose-derived stem cells into Schwann-like cells: a promise for treatment of demyelinating diseases. Adv Biomed Res 1:12

    Article  PubMed  Google Scholar 

  • Smith AG, Heath JK, Donaldson DD, Wong GG, Moreau J, Stahl M, Rogers D (1988) Inhibition of pluripotential embryonic stem cell differentiation by purified polypeptides. Nature 336:688–690

    Article  PubMed  CAS  Google Scholar 

  • Stankoff B, Aigrot MS, Noel F, Wattilliaux A, Zalc B, Lubetzki C (2002) Ciliary neurotrophic factor (CNTF) enhances myelin formation: a novel role for CNTF and CNTF-related molecules. J Neurosci 22:9221–9227

    PubMed  CAS  Google Scholar 

  • Stoll G, Muller HW (1999) Nerve injury, axonal degeneration and neural regeneration: basic insights. Brain Pathol 9:313–325

    Article  PubMed  CAS  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 25:7–15

    Article  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Xu Y, Liu Z, Liu L, Zhao C, Xiong F, Zhou C, Li Y, Shan Y, Peng F, Zhang C (2008b) Neurospheres from rat adipose-derived stem cells could be induced into functional Schwann cell-like cells in vitro. BMC Neurosci 12(9):21

    Article  Google Scholar 

  • Zang DW, Cheema SS (2003) Leukemia inhibitory factor promotes recovery of locomotor function following spinal cord injury in the mouse. J Neurotrauma 20:1215–1222

    Article  PubMed  Google Scholar 

  • Ziegler L, Grigoryan S, Yang IH, Thakor NV, Goldstein RS (2011) Efficient generation of Schwann cells from human embryonic stem cell-derived neurospheres. Stem Cell Rev 7:394–403

    Article  PubMed  Google Scholar 

  • Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, Alfonso ZC, Fraser JK, Benhaim P, Hedrick MH (2002) Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 13:4279–4295

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors are grateful to Iranian Council of Stem Cell Technology, Isfahan University of Medical Sciences for financial support (Grant No. 188055); and Dr. Freshteh Haghighat for providing human adipose tissue.

Conflict of interest

None

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Shahnaz Razavi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Razavi, S., Mardani, M., Kazemi, M. et al. Effect of Leukemia Inhibitory Factor on the Myelinogenic Ability of Schwann-Like Cells Induced from Human Adipose-Derived Stem Cells. Cell Mol Neurobiol 33, 283–289 (2013). https://doi.org/10.1007/s10571-012-9895-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10571-012-9895-2

Keywords

Navigation