MIDKINE THAT PROMOTES SURVIVAL OF FETAL HUMAN NEURONS IS PRODUCED BY FETAL HUMAN ASTROCYTES IN CULTURE

Midkine (MK), a retinoic acid responsive gene product, is a novel heparin-binding growth factor with an apparent molecular weight of 14-kDa. In fetal human neuron cultures, addition of recombinant human MK (10-100 ng/ml) resulted in a 3-fold increase in the number of surviving neurons under the serum-free culture condition. Production of MK was identified in the conditioned medium of astrocyte-enriched cultures by imunoblotting but not in the medium of neuron-enriched cultures. The level of MK production was not affected by treatment with retinoic acid. These results indicate that in the developing human central nervous system, astrocytes secrete MK that exhibits potent trophic activity to neurons.