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Phenotypic Modulation and Neuroprotective Effects of Olfactory Ensheathing Cells: a Promising Tool for Cell Therapy

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Abstract

Olfactory Ensheathing Cells (OECs), exhibiting phenotypic characteristics of both astrocytes and Schwann Cells, show peculiar plasticity. In vitro, OECs promote axonal growth, while in vivo they promote remyelination of damaged axons. We decided to further investigate OEC potential for regeneration and functional recovery of the damaged Central Nervous System (CNS). To study OEC antigen modulation, OECs prepared from postnatal mouse olfactory bulbs were grown in different culture conditions: standard or serum-free media with/without Growth Factors (GFs) and analyzed for different neural specific markers. OEC functional characterizations were also achieved. Resistance of OECs to the neurotoxin 6-hydroxydopamine (6-OHDA) was analyzed by evaluating apoptosis and death. OEC neuroprotective properties were investigated by in vitro co-cultures or by addition of OEC conditioned medium to the neuroblastoma SH-SY5Y cells exposed to 6-OHDA. We observed: 1) modification of OEC morphology, reduced cell survival and marker expression in serum-free medium; 2) GF addition to serum-free medium condition influenced positively survival and restored basal marker expression; 3) no OEC apoptosis after a prolonged exposition to 6-OHDA; 4) a clear OEC neuroprotective tendency, albeit non statistically significant, on 6-OHDA treated SH-SY5Y cells. These peculiar properties of OECs might render them potential clinical agents able to support injured CNS.

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Acknowledgments

We would like to thank Dr. Luigi Castoro for his useful technical help in the laboratory.

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Authors and Affiliations

  1. Institute of Neurological Sciences, CNR, Section of Catania, via Paolo Gaifami 18, 95126, Catania, Italy

    Rosalia Pellitteri

  2. Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, via Zucchi 18, 20095, Cusano Milanino, Milan, Italy

    Lidia Cova, Vincenzo Silani & Patrizia Bossolasco

  3. Department of Experimental Medicine, Section of Human Anatomy, University of Genoa, via De Toni 14, 16132, Genoa, Italy

    Damiano Zaccheo

  4. Department of Pathophysiology and Transplantation - “Dino Ferrari” Center, Università degli Studi di Milano, via Francesco Sforza 35, 20122, Milan, Italy

    Vincenzo Silani

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  1. Rosalia Pellitteri
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  2. Lidia Cova
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Correspondence to Rosalia Pellitteri.

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Electronic supplementary material

Suppl. Table 1

(DOC 38 kb)

Suppl. Table 2

(DOC 39 kb)

Suppl. Figure 1

Images by phase-contrast microscopy of representative fields of OECs grown in different conditions. On the left the figure shows OECs in serum (DMEM/FBS) and with GFs (bFGF or GDNF); on the right the figure shows OECs without serum (FBS-free DMEM) and with GFs (bFGF or GDNF). Scale bar 50 μm (GIF 1769 kb)

High Resolution Image (TIFF 21431 kb)

Suppl. Figure 2

Representative flow cytometry analysis of markers expression by OECs. (GIF 53 kb)

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Suppl. Figure 3

Effect of serum depletion on cell proliferation. (A): Number of OECs recovered after one week of culture with or without 10 % serum addition in the medium by Trypan blue exclusion. (B): Proliferation of the OECs after one week of culture with or without 10 % serum addition in the medium evaluated by MTS assay. (GIF 131 kb)

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Pellitteri, R., Cova, L., Zaccheo, D. et al. Phenotypic Modulation and Neuroprotective Effects of Olfactory Ensheathing Cells: a Promising Tool for Cell Therapy. Stem Cell Rev and Rep 12, 224–234 (2016). https://doi.org/10.1007/s12015-015-9635-3

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