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Stem Cell Reviews and Reports

, Volume 14, Issue 2, pp 200–212 | Cite as

Dual Contribution of Mesenchymal Stem Cells Employed for Tissue Engineering of Peripheral Nerves: Trophic Activity and Differentiation into Connective-Tissue Cells

  • F. Evaristo-Mendonça
  • A. Carrier-Ruiz
  • R. de Siqueira-Santos
  • R. M. P. Campos
  • B. Rangel
  • T. H. Kasai-Brunswick
  • V. T. Ribeiro-Resende
Article

Abstract

Adult peripheral nerves in vertebrates can regrow their axons and re-establish function after crush lesion. However, when there is extensive loss of a nerve segment, due to an accident or compressive damage caused by tumors, regeneration is strongly impaired. In order to overcome this problem, bioengineering strategies have been employed, using biomaterials formed by key cell types combined with biodegradable polymers. Many of these strategies are successful, and regenerated nerve tissue can be observed 12 weeks after the implantation. Mesenchymal stem cells (MSCs) are one of the key cell types and the main stem-cell population experimentally employed for cell therapy and tissue engineering of peripheral nerves. The ability of these cells to release a range of different small molecules, such as neurotrophins, growth factors and interleukins, has been widely described and is a feasible explanation for the improvement of nerve regeneration. Moreover, the multipotent capacity of MSCs has been very often challenged with demonstrations of pluripotency, which includes differentiation into any neural cell type. In this study, we generated a biomaterial formed by EGFP-MSCs, constitutively covering microstructured filaments made of poly-ε-caprolactone. This biomaterial was implanted in the sciatic nerve of adult rats, replacing a 12-mm segment, inside a silicon tube. Our results showed that six weeks after implantation, the MSCs had differentiated into connective-tissue cells, but not into neural crest-derived cells such as Schwann cells. Together, present findings demonstrated that MSCs can contribute to nerve-tissue regeneration, producing trophic factors and differentiating into fibroblasts, endothelial and smooth-muscle cells, which compose the connective tissue.

Keywords

Mesenchymal stem cells PCL filaments Tissue engineering Nerve regeneration Peripheral nervous system 

Abbreviations

α-SMA

alpha smooth muscle actin

ANOVA

analysis of variance

BDNF

brain-derived neurotrophic factor, CD-90, 45, 34, 29 and 31, cluster of differentiation 90, 45, 34, 29 and 31

DMEM

Dulbecco’s modified Eagle medium

DRG

dorsal root ganglia;

EC

endothelial cells

EDTA

ethylenediaminetetraacetic acid

EGFP

enhanced green fluorescent protein

hADSC

human adipose-derived stromal cells

MSCs

mesenchymal stem cells

NF-200

neurofilament-200

NGF

nerve growth factor

PBS

phosphate buffered saline

PCL

polycaprolactone

PF

paraformaldehyde

PNS

peripheral nervous system

SC

Schwann cells

VEGF

vascular endothelial growth factor

Notes

Acknowledgements

We thank Dr. Burkhard Schlosshauer from the NMI Reutlingen at Tübingen University for kindly donating the PCL filaments. This study was supported by grants and fellowships from the Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ) to V.T.R.R., F.E.M., and A.C.R.; and the Instituto Nacional de Neurociências Translacional (INNT) and the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) to V.T.R.R.

Authors’ contributions.

FEM: performed cell and embryonic cultures, generation of in-vivo experimental model, histology procedures, fluorescent imaging, statistical analysis, interpretation of experimental results, and manuscript development and writing. ACR: Performed histology, confocal microscopy, culture procedures, interpretation of experimental results and development and writing of the manuscript. RSS: Established DRG explants culture system, contributed to the interpretation of experimental results, and manuscript development and writing. VTRR: Director of the project. Contributed to the general administration, cell culture, generation of in-vivo experimental model, histology and staining procedures, fluorescence and electron microscopy, statistical analysis, interpretation of experimental results, and manuscript development and writing. All authors read and approved the manuscript.

Compliance with Ethical Standards

Competing Interests

The authors declare that they have no competing interests.

Supplementary material

12015_2017_9786_MOESM1_ESM.tif (6.2 mb)
Supplementary material 1 (TIF 6307 KB)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Instituto de Biofísica Carlos Chagas Filho, Laboratório de NeuroquímicaUniversidade Federal do Rio de JaneiroRio de JaneiroBrazil
  2. 2.Department of Neurophysiology, Graduate School of MedicineThe University of TokyoTokyoJapan
  3. 3.Centro Nacional de Biologia Estrutural e Bioimagem- CENABIOCidade UniversitáriaRio de JaneiroBrazil
  4. 4.Núcleo Multidisciplinar de Pesquisa em Biologia - Numpex-BioUniversidade Federal do Rio de JaneiroDuque de CaxiasBrazil
  5. 5.Programa de Neurobiologia, Instituto de Biofísica Carlos Chagas FilhoUFRJRio de JaneiroBrazil

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