The effects of peptide modified gellan gum and olfactory ensheathing glia cells on neural stem/progenitor cell fate.
The regenerative capacity of injured adult central nervous system (CNS) tissue is very limited. Specifically, traumatic spinal cord injury (SCI) leads to permanent loss of motor and sensory functions below the site of injury, as well as other detrimental complications. A potential regenerative strategy is stem cell transplantation; however, cell survival is typically less than 1%. To improve cell survival, stem cells can be delivered in a biomaterial matrix that provides an environment conducive to survival after transplantation. One major challenge in this approach is to define the biomaterial and cell strategies in vitro. To this end, we investigated both peptide-modification of gellan gum and olfactory ensheathing glia (OEG) on neural stem/progenitor cell (NSPC) fate. To enhance cell adhesion, the gellan gum (GG) was modified using Diels-Alder click chemistry with a fibronectin-derived synthetic peptide (GRGDS). Amino acid analysis demonstrated that approximately 300 nmol of GRGDS was immobilized to each mg of GG. The GG-GRGDS had a profound effect on NSPC morphology and proliferation, distinct from that of NSPCs in GG alone, demonstrating the importance of GRGDS for cell-GG interaction. To further enhance NSPC survival and outgrowth, they were cultured with OEG. Here NSPCs interacted extensively with OEG, demonstrating significantly greater survival and proliferation relative to monocultures of NSPCs. These results suggest that this co-culture strategy of NSPCs with OEG may have therapeutic benefit for SCI repair.
University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Guimarães, Portugal.
Nuno A
NA
Silva
Michael J
MJ
Cooke
Roger Y
RY
Tam
Nuno
N
Sousa
António J
AJ
Salgado
Rui L
RL
Reis
Molly S
MS
Shoichet
D000595:Amino Acid Sequence; D000818:Animals; D002450:Cell Communication / Q000187:drug effects; D019070:Cell Lineage / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D005353:Fibronectins / Q000737:chemistry; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000138:chemical synthesis / Q000737:chemistry; D008297:Male; D008969:Molecular Sequence Data; D058953:Neural Stem Cells / Q000166:cytology* / Q000187:drug effects*; D009457:Neuroglia / Q000166:cytology*; D009830:Olfactory Bulb / Q000166:cytology*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011135:Polysaccharides, Bacterial / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D005353:Fibronectins; D010455:Peptides; D011135:Polysaccharides, Bacterial; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; C048288:gellan gum