The development of heparan sulfate sugars as therapeutics: Versatility that couples stem cells, tissue engineering, and wound repair

The extracellular matrix (ECM) is a dynamically complex component of all tissues, especially during phases of growth and development. Although historically thought of as “ground substance” or “glycocalyx,” it actually functions as a scaffold for tissue morphogenesis, provides cues for cell proliferation and differentiation, promotes the maintenance of differentiated tissues, and both triggers and enhances the repair response after injury. Although various types of collagens, adhesion glycoproteins, growth factors, and chemokines are present in the extracellular matrices in tissue- and temporal-specific manners, a large fraction of the bioactivity is carried by its sugar component, and especially the heparan sulfate glycosaminoglycans. Because tissue morphogenesis is mediated by multiple ECM influences and by multiple active sites on these components, it is now becoming clear that heparan sulfates play major roles in orchestrating these complex arrangements, particularly during growth and repair processes. Because of their extractability, robustness, and resistance to chemical treatment, biologically active, ECM-derived sugars seem to be well placed for use in tissue repair, regeneration, and engineering. They also seem to have a promising future in “programming” stem cells for tissue replacement. Drug Dev. Res. 62:303–316, 2004. © 2004 Wiley-Liss, Inc.