Stem cells from the dental apical papilla in extracellular matrix hydrogels mitigate inflammation of microglial cells.
Natalija TaticFelicity R A J RoseAnne des RieuxLisa Jane WhitePublished in: Scientific reports (2019)
After spinal cord injury (SCI) chronic inflammation hampers regeneration. Influencing the local microenvironment after SCI may provide a strategy to modulate inflammation and the immune response. The objectives of this work were to determine whether bone or spinal cord derived ECM hydrogels can deliver human mesenchymal stem cells from the apical papilla (SCAP) to reduce local inflammation and provide a regenerative microenvironment. Bone hydrogels (8 and 10 mg/ml, B8 and B10) and spinal cord hydrogels (8 mg/ml, S8) supplemented with fibrin possessed a gelation rate and a storage modulus compatible with spinal cord implantation. S8 and B8 impact on the expression of anti and pro-inflammatory cytokines (Arg1, Nos2, Tnf) in LPS treated microglial cells were assessed using solubilised and solid hydrogel forms. S8 significantly reduced the Nos2/Arg1 ratio and solubilised B8 significantly reduced Tnf and increased Arg1 whereas solid S8 and B8 did not impact inflammation in microglial cells. SCAP incorporation within ECM hydrogels did not impact upon SCAP immunoregulatory properties, with significant downregulation of Nos2/Arg1 ratio observed for all SCAP embedded hydrogels. Tnf expression was reduced with SCAP embedded in B8, reflecting the gene expression observed with the innate hydrogel. Thus, ECM hydrogels are suitable vehicles to deliver SCAP due to their physical properties, preservation of SCAP viability and immunomodulatory capacity.
Keyphrases
- extracellular matrix
- stem cells
- spinal cord
- drug delivery
- hyaluronic acid
- oxidative stress
- induced apoptosis
- tissue engineering
- spinal cord injury
- immune response
- wound healing
- neuropathic pain
- gene expression
- cell cycle arrest
- drug release
- inflammatory response
- rheumatoid arthritis
- dna methylation
- signaling pathway
- lps induced
- endothelial cells
- bone mineral density
- binding protein
- mental health
- bone marrow
- physical activity
- cell death
- soft tissue
- nitric oxide
- dendritic cells
- long non coding rna
- postmenopausal women
- bone loss