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Transplantation of Human Skin-Derived Mesenchymal Stromal Cells Improves Locomotor Recovery After Spinal Cord Injury in Rats

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Abstract

Spinal cord injury (SCI) is a devastating neurologic disorder with significant impacts on quality of life, life expectancy, and economic burden. Although there are no fully restorative treatments yet available, several animal and small-scale clinical studies have highlighted the therapeutic potential of cellular interventions for SCI. Mesenchymal stem cells (MSCs)—which are conventionally isolated from the bone marrow—recently emerged as promising candidates for treating SCI and have been shown to provide trophic support, ameliorate inflammatory responses, and reduce cell death following the mechanical trauma. Here we evaluated the human skin as an alternative source of adult MSCs suitable for autologous cell transplantation strategies for SCI. We showed that human skin-derived MSCs (hSD-MSCs) express a range of neural markers under standard culture conditions and are able to survive and respond to neurogenic stimulation in vitro. In addition, using histological analysis and behavioral assessment, we demonstrated as a proof-of-principle that hSD-MSC transplantation reduces the severity of tissue loss and facilitates locomotor recovery in a rat model of SCI. Altogether, the study provides further characterization of skin-derived MSC cultures and indicates that the human skin may represent an attractive source for cell-based therapies for SCI and other neurological disorders. Further investigation is needed to elucidate the mechanisms by which hSD-MSCs elicit tissue repair and/or locomotor recovery.

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Acknowledgments

This work was supported by the Ministério da Saúde (MS-SCTIE-DECIT), Ministério da Ciência, Tecnologia e Inovação/Conselho Nacional de Desenvolvimento Científico e Tecnológico (MCTI/CNPq/Brazil), CNPq/PIBIC/PIBIT (Brazil), Coordenação de Aperfeiçamento de Pessoal de Nível Superior (CAPES, Brazil), Instituto Nacional de Neurociência Translacional (MCTI/INNT), and Fundação de Amparo à Pesquisa do Estado de Santa Catarina (FAPESC, Brazil). RBB is supported by a fellowship from the Science Without Borders Program (CAPES, Brazil).

Author Contributions

Conceived and designed the experiments: FRM, RBB, SF, GAR, AGT. Performed the experiments: FRM, SF, ACM, MR, PBD. Analyzed the data: FRM, SF, ACM, RBB, CPF. Wrote the manuscript: RBB, CPF, AGT.

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    Authors and Affiliations

    1. Departamento de Biologia Celular, Embriologia e Genética, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, Florianópolis, SC, 88040-900, Brazil

      Fernanda Rosene Melo, Michele Rode, Priscilla Barros Delben & Andrea Gonçalves Trentin

    2. Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, Florianópolis, SC, Brazil

      Stefânia Forner, Alessandra Cadete Martini & Giles Alexander Rae

    3. MRC Centre for Regenerative Medicine, The University of Edinburgh, Edinburgh, UK

      Raul Bardini Bressan

    4. Faculdade de Farmácia, Centro de Ciências Da Saúde, Universidade Federal Do Rio de Janeiro, Campus Universitário, Ilha do Fundão, Rio de Janeiro, RJ, Brazil

      Claudia Pinto Figueiredo

    Authors
    1. Fernanda Rosene Melo
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    2. Raul Bardini Bressan
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    3. Stefânia Forner
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    8. Claudia Pinto Figueiredo
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    9. Andrea Gonçalves Trentin
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    Correspondence to Andrea Gonçalves Trentin.

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    Additional information

    Fernanda Rosene Melo, Raul Bardini Bressan, Stefânia Forner have contributed equally to this work.

    Electronic Supplementary Material

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    Supplementary material 1 (DOCX 18 kb)

    10571_2016_414_MOESM2_ESM.pdf

    Supplementary Fig S1 Percentage of ßIII-tubulin- and GFAP-positive in the different cultures conditions tested. Values represent the percentage of posive cells in relation to total cell number are expressed as mean ± S.E.M of 20 random fields in three independent experiments. Differences were not statistically significant by one-way ANOVA. (PDF 61 kb)

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    Melo, F.R., Bressan, R.B., Forner, S. et al. Transplantation of Human Skin-Derived Mesenchymal Stromal Cells Improves Locomotor Recovery After Spinal Cord Injury in Rats. Cell Mol Neurobiol 37, 941–947 (2017). https://doi.org/10.1007/s10571-016-0414-8

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    • DOI: https://doi.org/10.1007/s10571-016-0414-8

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