INJECTION OF A HEPARAN-SULFATE LIKE SUBST ANCE IN A CRUSHED MUSCLE ACCELERATES ITS REGENERATION

Dextran derivatives were obtained by controlled successive substitutio ns of carboxymethyl, carbomethyl-benzylamide and carboxymethyl-benzyla mide sulfonate groups on glucose residues. Among these derivatives, RG T11 was selected since it mimicked same properties of heparin or hepar an sulfate to stabilise and protect heparin binding growth factors suc h as FGFs and TGF-beta. Furthermore RGT11 inhibited plasmine and leuko cyte elastase. In previous works, we have explained the healing effect s of RGT obtained in skin or bone repair models by these protecting an d inhibiting properties. We now present the results obtained after a s ingle injection of RGT11 in a regenerating crushed extensor digitorum longus (EDL) muscle. After 8 days, RGT11 injected muscles contained 10 times the number of fibers than controlled injected muscles. Fibers w ere organized in bundles of normal size. Histological analysis indicat ed that regeneration was comparable to that observed after 3 weeks wit hout RGT. Hence in vivo, RGT11 could act by protecting the heparin bin ding growth factors involved in the natural process of muscle regenera tion and therefore favour their actions. This family of polymers shoul d offer a new pharmaceutical potential for treating muscle atrophy and destruction and is worth studying further.