Glial cells metabolically cooperate: a potential requirement for gene replacement therapy.

Immunofluorescently labeled glial cells are shown by radioautography to metabolically cooperate with hypoxanthine phosphoribosyltransferase-deficient fibroblasts. The observations of cooperation without cell contact and of incorporation gradients around the glial cells suggest that cooperation occurs through extracellular transport of radiolabeled purine compounds. The transfer of radiolabeled adenine, adenosine, or methylthioadeninosine is supported by the quantitative loss of cooperation when the recipient cell is also deficient in enzymes required for adenine or adenosine salvage. The demonstration of glial cell cooperation provides impetus for current research toward gene replacement therapy for the neurologic symptoms of the Lesch-Nyhan syndrome.