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Adipose tissue-derived stromal cells (ADSC) express oligodendrocyte and myelin markers, but they do not function as oligodendrocytes

Histochemistry and Cell Biology volume 148, pages 503–515 (2017)Cite this article

Abstract

Mesenchymal cells cultured from the vasculo-stromal fraction of adipose tissue (ADSC) show adult stem cell characteristics and several groups have claimed generating neural cells from them. However, we have observed that many markers commonly used for the identification of neural cells are spontaneously expressed by ADSC in culture. In the present study, we have examined the expression of characteristic oligodendrocyte molecules in cultured ADSC, aiming to test if myelinating cells could be generated from accessible non-neural adult tissues. In basal growth conditions, rat ADSC spontaneously expressed CNPase, MBP, MOG, protein zero, GAP43, Sox10, and Olig2, as shown by immunocytrochemistry and western blot. A small population of cultured ADSC expressed membrane galactocerebroside (O1 antibody), but no cell stained with O4 antibody. RT-PCR analyses showed the expression of CNPase, MBP, DM20, and low levels of Olig2, Sox10, and Sox2 mRNA by rat ADSC. When rat ADSC were treated with combinations of factors commonly used in neural-inducing media (retinoic acid, dbcAMP, EGF, basic FGF, NT3, and/or PDGF), the number of O1-positive cells changed, but in no case, mRNA expression of Sox10 and Olig2 transcription factors approached CNS oligodendrocyte levels. In co-culture with rat dorsal root ganglion neurons, no sign of axonal myelination by rat ADSC was observed. These studies show that the expression of oligodendrocyte traits by cultured ADSC is not a proof of functional competence as oligodendroglia and suggest that in culture conditions, ADSC acquire intermediate, uncommitted phenotypes.

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Fig. 1
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Fig. 4

Abbreviations

ADSC:

Adipose tissue-derived stromal cells

CNPase:

2′,3′-Cyclic-nucleotide 3′-phosphodiesterase

DRG:

Dorsal root ganglion

GalC:

Galactocerebroside, galactosylceramide

GAP43:

Growth-associated protein

MSC:

Mesenchymal stem cells

MBP:

Myelin basic protein

MOG:

Myelin oligodendrocyte glycoprotein

NG2:

Neural/glial antigen 2 (chondroitin sulfate proteoglycan 4)

p75NTR:

Low-affinity NGF receptor, p75

P0:

Myelin protein zero

PLP1:

Myelin proteolipid protein

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Acknowledgements

We thank the help of Prof. M.V. Toledo-Lobo in various parts of the study and in S.M. Fig. 6, of Dr. E. Rodríguez-Martín in cytometry included in S.M. Fig. 8 and of Drs. M.L. Hernández-Bule and M.A. Martínez in ADSC multipotentiality tests. This work was supported by the Agencia Laín Entralgo, Comunidad de Madrid NDG09/14 and Project VEXEM 2014/0023.

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  1. Servicio de Neurobiología-Investigación, IRYCIS, Hospital Universitario Ramón y Cajal, Carretera de Colmenar km 9, 28034, Madrid, Spain

    Lara Vellosillo, Maria Paz Muñoz & Carlos Luis Paíno

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  1. Lara Vellosillo
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  2. Maria Paz Muñoz
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  3. Carlos Luis Paíno
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Contributions

LV designed and performed experiments and data analysis and contributed with manuscript writing. MPM performed experiments. CLP coordinated the study, designed and performed experiments and data analysis, and wrote the manuscript.

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Correspondence to Carlos Luis Paíno.

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Vellosillo, L., Muñoz, M.P. & Paíno, C.L. Adipose tissue-derived stromal cells (ADSC) express oligodendrocyte and myelin markers, but they do not function as oligodendrocytes. Histochem Cell Biol 148, 503–515 (2017). https://doi.org/10.1007/s00418-017-1588-y

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  • DOI: https://doi.org/10.1007/s00418-017-1588-y

Keywords

  • Mesenchymal stem cells
  • Oligodendrocyte
  • Galactocerebroside
  • Myelin proteins
  • Myelination in culture