Heparan Sulfate: A Potential Candidate for the Development of Biomimetic Immunomodulatory Membranes

Abstract

Clinical trials have demonstrated that heparan sulfate (HS) could be used as a therapeutic agent for the treatment of inflammatory diseases. Its anti-inflammatory effect makes it suitable for the development of biomimetic innovative strategies aiming at modulating stem cells behavior toward a pro-regenerative phenotype in case of injury or inflammation. Here, we propose collagen type I meshes fabricated by solvent casting and further crosslinked with HS (HS-Col) to create a biomimetic environment resembling the extracellular matrix of soft tissue. HS-Col meshes were tested for their capability to provide physical support to stem cells’ growth, maintain their phenotypes and immunosuppressive potential following inflammation. HS-Col effect on stem cells was investigated in standard conditions as well as in an inflammatory environment recapitulated in vitro through a mix of pro-inflammatory cytokines (tumor necrosis factor-α and interferon-gamma; 20 ng/ml). A significant increase in the production of molecules associated with immunosuppression was demonstrated in response to the material and when cells were grown in presence of pro-inflammatory stimuli, compared to bare collagen membranes (Col), leading to a greater inhibitory potential when mesenchymal stem cells were exposed to stimulated peripheral blood mononuclear cells. Our data suggest that the presence of HS is able to activate the molecular machinery responsible for the release of anti-inflammatory cytokines, potentially leading to a faster resolution of inflammation.

Improving the immunosuppressive potential of articular chondroprogenitors in a three-dimensional culture setting

“…We have previously demonstrated an increased immunosuppressive capacity of stem cells when cultured in a 3D setting using a biomimetic collagen-made scaffold 28 , 38 . Thus, we hypothesized that a porous scaffold would enhance the immunomodulatory properties of human BMMSC and CPSC.…”

Amphibian regeneration and mammalian cancer: Similarities and contrasts from an evolutionary biology perspective

“…[45] Our group, among many others, has been successful in monitoring the molecular and cellular cascades activated by the implant of biomimetic and immunomodulatory materials. [46,47] With the admixture of the bioactive macromolecule chondroitin sulfate and the architectural complexity and mechanical properties of the scaffold material, we have developed a pro-regenerative environment able to localize macrophages at the site of implantation. Analysis of macrophages colonizing our developed scaffold material shows the presence of alternatively-activated cells (anti-inflammatory macrophages, or M2 macrophages), which we tentatively believe are responsible for activating the biological processes associated with the extracellular matrix (ECM) formation, collagen fibril reorganization, angiogenesis, and tissue morphogenesis, ultimately leading to the complete integration of the scaffold within the tissue.…”

<i>FAM20A</i> is Dispensable for Dentinogenesis and Osteogenesis

“…Fam20c has been proved the causative gene for human Raine Syndrome manifested by lethal sclerosis bone dyspalsia or hypophosphetamia rickets [10][11][12] . Inactivation of Fam20c in ectoderm leads to Amelogenesis Imperfecta 13,14) , while abrogation of Fam20c in mesenchyme results in Dentinogenesis Imperfecta and osteoporosis 14,15) . Fam20c deficiency in mice not only reduces the expression and phosphorylation of the extracellular matrices in enamel, dentin and bone [16][17][18] , but also elongates the half-time of serum FGF23 19,20) , which enhances phosphorus excretion and decreases serum phosphorus.…”