[Acceleration of the regeneration of skeletal muscles in adult rats by dextran derivatives].
Dextran derivatives were obtained by controlled successive substitutions of carboxymethyl, carbomethyl-benzylamide and carboxymethyl-benzylamide sulfonate groups on glucose residues. Among these derivatives, RGT11 was selected since it mimicked some properties of heparin or heparan sulfate to stabilise and protect heparin binding growth factors such as FGFs and TGF-beta. Furthermore RGT11 inhibited plasmine and leukocyte elastase. In previous works, we have explained the healing effects of RGT obtained in skin or bone repair models by these protecting and inhibiting properties. We now present the results obtained after a single 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 were organized in bundles of normal size. Histological analysis indicated that regeneration was comparable to that observed after 3 weeks without RGT. Hence in vivo, RGT11 could act by protecting the heparin binding growth factors involved in the natural process of muscle regeneration and therefore favour their actions. This family of polymers should offer a new pharmaceutical potential for treating muscle atrophy and destruction and is worth studying further.
Gautron
J
J
Laboratoires CRRET, URA-CNRS, Université de Paris-XII, Créteil, France.
Kedzia
C
C
Husmann
I
I
Barritault
D
D
D000818:Animals; D016264:Dextran Sulfate / Q000494:pharmacology; D003911:Dextrans / Q000494:pharmacology*; D008297:Male; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology*; D010952:Plasma Substitutes / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration / Q000187:drug effects*
D003911:Dextrans; D010952:Plasma Substitutes; D016264:Dextran Sulfate