Sulfated polysaccharides interact with fibroblast growth factors and protect from denaturation

Abstract

Fibroblast growth factors (FGFs) regulate embryonic development and homeostasis, including tissue and organ repair and specific aspects of metabolism. The basic FGF and acidic FGF, now known as FGF2 and FGF1, are widely used protein drugs for tissue repair. However, they are susceptible to denaturation at ambient temperatures and during long‐time storage, which will reduce their biological activity. The interaction of FGFs with the sulfated domains of heparan sulfate and heparin is essential for their cellular signaling and stability. Therefore, we analyzed the interactions of FGF1 and FGF2 with four sulfated polysaccharides: heparin, dextran sulfate (DXS), λ‐carrageenan, and chondroitin sulfate. The results of thermal stability and cell proliferation assays demonstrate that heparin, DXS, and λ‐carrageenan bound to both FGFs and protected them from denaturation. Our results suggest heparin, DXS, and λ‐carrageenan are potential formulation materials that bind and stabilize FGFs, and which may also potentiate their activity and control their delivery.

Effect of Enzymatically Extracted Fucoidans on Angiogenesis and Osteogenesis in Primary Cell Culture Systems Mimicking Bone Tissue Environment

“…We applied fucoidan as a free molecule in solution to the cell culture systems, whereas a lot of studies investigated the bioactivity of fucoidans incorporated in a delivery system. As reported for other sulfated sugars [ 41 , 42 ], also fucoidans seem to be able to bind growth factors like VEGF and their receptors. Supporting the assumption that fucoidans are able to bind to VEGF, we showed in an ELISA-based competitive binding assay that the tested extracts suppress the binding of VEGF to its antibody in a concentration-dependent manner ( Figure S1 ).…”

Synthetic polymers as xeno-free materials for stabilizing basic fibroblast growth factor in human mesenchymal stem cell cultures

“…In a previous study, heparin and dextran sulfate were reported to protect bFGF from denaturation [ 9 ], and the effective lowest protecting concentration for 5 μM of bFGF was reported as 5–25 μg/mL. In our results, the effective concentration of the dextran sulfate for cell proliferation was 25 ng/mL in a medium containing 60 ng/mL (3.5 nM, FW 17,000) of bFGF.…”

“…It is also recommended that these media should be stored at 4 °C after the addition of supplements to the basal media, and be used within 1 week. Considerable efforts have been made in the delivery and formulation of bFGF and other proteins to stabilize them for therapeutic purposes [ [9] , [10] , [11] ], but there has been limited research on stabilizing bFGF in the cell culture media.…”

Polysaccharide-Based Materials Created by Physical Processes: From Preparation to Biomedical Applications

“…Furthermore, the heparin stabilizes the FGF-2-FGFR-1 complex, promoting receptor dimerization and thereby facilitating GF signal transduction [ 277 ]. The protection afforded by binding to heparin extends to other sulfated polysaccharides as well, including sulfonated dextran, dextran sulfate, lambda -carrageenan, and chondroitin sulfate [ 262 , 278 ]. Heparin has similar effects on other growth factors.…”