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Olfactory Ensheathing Cells Promote Differentiation of Neural Stem Cells and Robust Neurite Extension

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Abstract

Aims

The goal of this study was to gain insight into the signaling between olfactory ensheathing cells (OECs) and neural stem cells (NSCs). We sought to understand the impact of OECs on NSC differentiation and neurite extension and to begin to elucidate the factors involved in these interactions to provide new targets for therapeutic interventions.

Materials and Methods

We utilized lines of OECs that have been extremely well characterized in vitro and in vivo along with well studied NSCs in gels to determine the impact of the coculture in three dimensions. To further elucidate the signaling, we used conditioned media from the OECs as well as fractioned components on NSCs to determine the molecular weight range of the soluble factors that was most responsible for the NSC behavior.

Results

We found that the coculture of NSCs and OECs led to robust NSC differentiation and extremely long neural processes not usually seen with NSCs in three dimensional gels in vitro. Through culture of NSCs with fractioned OEC media, we determined that molecules larger than 30 kDa have the greatest impact on the NSC behavior.

Conclusions

Overall, our findings suggest that cocultures of NSCs and OECs may be a novel combination therapy for neural injuries including spinal cord injury (SCI). Furthermore, we have identified a class of molecules which plays a substantial role in the behavior that provides new targets for investigating pharmacological therapies.

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Acknowledgments

The authors have no conflicts of interest. The authors would like to acknowledge NIH Director’s New Innovator Award Grant, DP20D007338. The authors would also like to acknowledge J. Silver for the generous gift of the OEC cell lines.

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Authors and Affiliations

  1. Harvard Medical School, 25 Shattuck Street, Boston, MA, 02115, USA

    Rosh Sethi & Roshan Sethi

  2. Precision Spine Care, 1814 Roseland Blvd, Suite 200, Tyler, TX, 75701, USA

    Andy Redmond

  3. Biomedical Engineering, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH, 44106, USA

    Erin Lavik

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  1. Rosh Sethi
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Correspondence to Erin Lavik.

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Rosh Sethi and Roshan Sethi contributed equally

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Sethi, R., Sethi, R., Redmond, A. et al. Olfactory Ensheathing Cells Promote Differentiation of Neural Stem Cells and Robust Neurite Extension. Stem Cell Rev and Rep 10, 772–785 (2014). https://doi.org/10.1007/s12015-014-9539-7

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