Journal of Molecular Neuroscience

, Volume 55, Issue 1, pp 91–98 | Cite as

Glial-Like Differentiation Potential of Human Mature Adipocytes

  • Antonella Poloni
  • Giulia Maurizi
  • Federica Foia
  • Eleonora Mondini
  • Domenico Mattiucci
  • Patrizia Ambrogini
  • Davide Lattanzi
  • Stefania Mancini
  • Massimo Falconi
  • Saverio Cinti
  • Attilio Olivieri
  • Pietro Leoni
Article

Abstract

The potential ability to differentiate dedifferentiated adipocytes into a neural lineage is attracting strong interest as an emerging method of producing model cells for the treatment of a variety of neurological diseases. Here, we describe the efficient conversion of dedifferentiated adipocytes into a neural-like cell population. These cells grew in neurosphere-like structures and expressed a high level of the early neuroectodermal marker Nestin. These neurospheres could proliferate and express stemness genes, suggesting that these cells could be committed to the neural lineage. After neural induction, NeuroD1, Sox1, Double Cortin, and Eno2 were not expressed. Patch clamp data did not reveal different electrophysiological properties, indicating the inability of these cells to differentiate into mature neurons. In contrast, the differentiated cells expressed a high level of CLDN11, as demonstrated using molecular method, and stained positively for the glial cell markers CLDN11 and GFAP, as demonstrated using immunocytochemistry. These data were confirmed by quantitative results for glial cell line-derived neurotrophic factor production, which showed a higher secretion level in neurospheres and the differentiated cells compared with the untreated cells. In conclusion, our data demonstrate morphological, molecular, and immunocytochemical evidence of initial neural differentiation of mature adipocytes, committing to a glial lineage.

Keywords

Dedifferentiated adipocytes Neurosphere Differentiation Glial-like cells 

References

  1. Anghileri E, Marconi S, Pignatelli A et al (2008) Neuronal differentiation potential of human adipose-derived mesenchymal stem cells. Stem Cells Dev 17(5):909–916PubMedCrossRefGoogle Scholar
  2. Colter DC, Class R, Di Girolamo CM, Prockop DJ (2000) Rapid expansion of recycling stem cells in cultures of plastic-adherent cells from human bone marrow. Proc Natl Acad Sci U S A 97:3213–3218PubMedCentralPubMedCrossRefGoogle Scholar
  3. De Matteis R, Zingaretti MC, Murano I et al (2009) In vivo physiological transdifferentiation of adult adipose cells. Stem Cells 27(11):2761–2768PubMedCrossRefGoogle Scholar
  4. Gage FH, Coates PW, Palmer TD (1995a) Survival and differentiation of adult neuronal progenitor cells transplanted to the adult brain. Proc Natl Acad Sci U S A 92:11879–11883PubMedCentralPubMedCrossRefGoogle Scholar
  5. Gage FH, Ray J, Fisher LJ (1995b) Isolation, characterization, and use of stem cells from the CNS. Annu Rev Neurosci 18:159–192PubMedCrossRefGoogle Scholar
  6. Hermann A, Gastl R, Liebau S et al (2004) Efficient generation of neural stem cell-like cells from adult human bone marrow stromal cells. J Cell Sci 117:4411–4422PubMedCrossRefGoogle Scholar
  7. Javazon EH, Colter DC, Schwarz EJ, Prockop DJ (2001) Rat marrow stromal cells are more sensitive to plating density and expand more rapidly from single-cell derived colonies than human marrow stromal cells. Stem Cells 19:219–225PubMedCrossRefGoogle Scholar
  8. Jiang Y, Jahagirdar BN, Reinhardt RL et al (2002) Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 418:41–49PubMedCrossRefGoogle Scholar
  9. Jiang Y, Henderson D, Blackstad M et al (2003) Neuroectodermal differentiation from mouse multipotent adult progenitor cells. Proc Natl Acad Sci U S A 100:11854–11860PubMedCentralPubMedCrossRefGoogle Scholar
  10. Johansson CB, Momma S, Clarke DL et al (1999) Identification of a neural stem cell in the adult mammalian central nervous system. Cell 96:25–34PubMedCrossRefGoogle Scholar
  11. Jumabay M, Abdmaulen R, Ly A et al (2014) Pluripotent stem cells derived from mouse and human white mature adipocytes. Stem Cells Transl Med 3(2):161–171PubMedCentralPubMedCrossRefGoogle Scholar
  12. Liu J, Song L, Jiang C et al (2012) Electrophysiological properties and synaptic function of mesenchymal stem cells during neurogenic differentiation—a mini-review. Int J Artif Organs 35(5):323–337PubMedCrossRefGoogle Scholar
  13. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCt method. Methods 25(4):402–408PubMedCrossRefGoogle Scholar
  14. Lu P, Blesch A, Tuszynski MH (2004) Induction of bone marrow stromal cells to neurons: differentiation, transdifferentiation, or artifact? J Neurosci Res 77(2):174–191PubMedCrossRefGoogle Scholar
  15. Matsumoto T, Kano K, Kondo D et al (2008) Mature adipocyte-derived dedifferentiated fat cells exhibit multilineage potential. J Cell Physiol 215(1):210–222PubMedCrossRefGoogle Scholar
  16. Mizuno H (2009) Adipose-derived stem cells for tissue repair and regeneration: ten years of research and a literature review. J Nihon Med Sch 76(2):56–66CrossRefGoogle Scholar
  17. Neuhuber B, Gallo G, Howard L et al (2004) Reevaluation of in vitro differentiation protocols for bone marrow stromal cells: disruption of actin cytoskeleton induces rapid morphological changes and mimics neuronal phenotype. J Neurosci Res 77(2):192–204PubMedCrossRefGoogle Scholar
  18. Pereira RF, Halford KW, O’Hara MD et al (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147CrossRefGoogle Scholar
  19. Poloni A, Maurizi G, Leoni P et al (2012) Human dedifferentiated adipocytes show similar properties to bone marrow-derived mesenchymal stem cells. Stem Cells 30(5):965–974PubMedCrossRefGoogle Scholar
  20. Renfranz PJ, Cunningham MG, McKay RDG (1991) Region-specific differentiation of hippocampal stem cell line HiB5 upon implantation into the developing mammalian brain. Cell 66:713–729PubMedCrossRefGoogle Scholar
  21. Reynolds BA, Weiss S (1992) Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 255:1707–1710PubMedCrossRefGoogle Scholar
  22. Sanchez-Ramos J, Song S, Cardozo-Pelaez F et al (2000) Adult bone marrow stromal cells differentiate into neural cells in vitro. Exp Neurol 164:247–256PubMedCrossRefGoogle Scholar
  23. Scuteri A, Miloso M, Foudah D et al (2011) Mesenchymal stem cells neuronal differentiation ability: a real perspective for nervous system repair? Curr Stem Cell Res Ther 6(2):82–92PubMedCrossRefGoogle Scholar
  24. Wei S, Zan L, Hausman GJ et al (2013) Dedifferentiated adipocyte-derived progeny cells (DFAT cells): potential stem cells of adipose tissue. Adipocyte 2(3):122–127PubMedCentralPubMedCrossRefGoogle Scholar
  25. Westerlund U, Moe MC, Varghese M et al (2003) Stem cells from the adult human brain develop into functional neurons in culture. Exp Cell Res 289:378–383PubMedCrossRefGoogle Scholar
  26. Wislet-Gendebien S, Hans G, Leprince P et al (2005) Plasticity of cultured mesenchymal stem cells: switch from Nestin -positive to excitable neuron-like phenotype. Stem Cells 23:392–402PubMedCrossRefGoogle Scholar
  27. Woodbury D, Schwarz EJ, Prockop DJ, Black IB (2000) Adult rat and human bone marrow stromal cells differentiate into neurons. J Neurosci Res 61:364–370PubMedCrossRefGoogle Scholar
  28. Yang Q, Mu J, Li Q et al (2008) A simple and efficient method for deriving neurospheres from bone marrow stromal cells. Biochem Biophys Res Commun 372(4):520–524PubMedCrossRefGoogle Scholar
  29. Zhang HH, Kumar S, Barnett AH, Eggo MC (2000) Ceiling culture of mature human adipocytes: use in studies of adipocyte functions. J Endocrinol 164(2):119–128PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Antonella Poloni
    • 1
  • Giulia Maurizi
    • 1
  • Federica Foia
    • 1
  • Eleonora Mondini
    • 2
  • Domenico Mattiucci
    • 1
  • Patrizia Ambrogini
    • 3
  • Davide Lattanzi
    • 3
  • Stefania Mancini
    • 1
  • Massimo Falconi
    • 4
  • Saverio Cinti
    • 2
  • Attilio Olivieri
    • 1
  • Pietro Leoni
    • 1
  1. 1.Clinica di Ematologia, Dipartimento di Scienze Cliniche e MolecolariUniversità Politecnica delle MarcheAnconaItaly
  2. 2.Dipartimento di Medicina Sperimentale e ClinicaUniversità Politecnica delle MarcheAnconaItaly
  3. 3.Dipartimento di Scienze della Terra, della Vita e dell’Ambiente, Sezione di FisiologiaUniversità di Urbino Carlo BoUrbinoItaly
  4. 4.Clinica Chirurgia del PancreasUniversità Politecnica delle Marche, Ospedali RiunitiAnconaItaly

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