4.8 Article

Combination of a peptide-modified gellan gum hydrogel with cell therapy in a lumbar spinal cord injury animal model

Journal

BIOMATERIALS
Volume 105, Issue -, Pages 38-51

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2016.07.019

Keywords

Spinal cord injury; Regenerative medicine; Adipose tissue-derived Stromal/Stem Cells; Olfactory Ensheathing Cells; Extracellular matrix like hydrogels

Funding

  1. Premios Santa Casa Neurociencias - Prize Melo e Castro for Spinal Cord Injury Research
  2. Portuguese Foundation for Science and Technology [SFRH/BD/103075/2014, SFRH/BPD/97701/2013]
  3. Northern Portugal Regional Operational Programme (NORTE), under the Portugal Partnership Agreement, through the European Regional Development Fund (FEDER) [NORTE-01-0145-FEDER-000013]
  4. FEDER funds, through the Competitiveness Factors Operational Programme (COMPETE)
  5. National funds, through the Foundation for Science and Technology (FCT) [POCI-01-0145-FEDER-007038]
  6. Fundação para a Ciência e a Tecnologia [SFRH/BD/103075/2014] Funding Source: FCT

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Spinal Cord Injury (SCI) is a highly incapacitating condition for which there is still no cure. Current clinical approaches are mainly based on palliative care, so there is a need to find possible treatments to SCI. Cellular transplantation is regarded with great expectation due to the therapeutic potential of cells such as Adipose tissue-derived Stromal/Stem Cells (ASCs) or Olfactory Ensheathing Cells (OECs). Both are accessible sources and present positive paracrine and cell-to-cell interactions, previously reported by our group. Additionally, biomaterials such as hydrogels have been applied in SCI repair with promising results. We propose to combine a GRGDS-modified gellan gum hydrogel with ASCs and OECs in order to promote SCI regeneration. In vitro, ASCs and OECs could be co-cultured within GG-GRGDS hydrogels inducing a more robust neurite outgrowth when compared to controls. In vivo experiments in a hemisection SCI rat model revealed that the administration of ASCs and OECs encapsulated in a GG-GRGDS hydrogel led to significant motor improvements when compared to both control (SCI) and hydrogel alone (GG-GRGDS) groups. This was accompanied by a decreased infiltration of inflammatory cells and astrocytes, and by an increased intensity of neurofilament. These results suggest evident gains induced by the encapsulation of ASCs and OECs in GG-GRGDS based hydrogels. (C) 2016 Elsevier Ltd. All rights reserved.

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