(2) Reconstructed Glycosaminoglycans (GAG)
Glycosaminoglycans (GAG) such as heparin and chondroitin sulfate are polysaccharides having sulfate groups with homogeneous configuration. They are one of the important constituents of extracellular matrix. NeTech has successfully reconstructed GAG by chemically cleaving GAG followed by polymer formation with vinyl monomers. The reconstructed GAG can effectively control cell binding, cell growth and the like. For example, reconstructed GAG with heparin (R-Hep) inhibits angiogenesis due to the fact that heparin binds to growth factor and suppresses cell proliferation. This may be illustrated by cultivation of human vascular endothelial cells (HUVEC) in medium containing R-Hep. Photo below clearly demonstrates inhibition of HUVEC tubular formation by R-Hep.
　
Anti-tumor activity of R-Hep is confirmed with mice cutaneously injected B-16 melanoma (Fig. 2).
　
HUVEC tubular formation
(Untreated)
Inhibited HUVEC tubular formation
(R-Hep treated)
　
Tumor with melanoma disappeared from mice treated by R-Hep during 8 days, while control mice without treatment remained apparent tumor within 8 days after tumor formation.
　
(Untreated) (R-Hep treated)

Fig. 2 Anti-tumor activity of R-Hep
　
PTCA (percutaneous transluminal coronary angioplasty) is widely used for treatment of ischemic heart diseases but this treatment induces restenosis through growth stimulation of vascular smooth muscle cells. R-Hep specifically inhibits smooth muscle cell growth to lead inhibition of restenosis. Fig. 3 shows restenosis of balloon-injured rat carotid artery with control animal (left), but restenosis is not seen with rat having received R-Hep using infusion pump (right).
　
Untreated
R-Hep treated

Fig. 3 Effect of R-Hep on restenosis inhibition
On the other hand, reconstructed GAG such as R-Hep and R-Con (containing chondroitin sulfate) stimulate other cells like fibroblasts, cartilage cells, and embryonic stem (ES) cells. Culture substrate complex of these GAG derivatives with collagen offers model of functional extracellular matrix.