Long-Term Tissue Culture of Neuroblastomas. II. Morphologic Evidence for Differentiation and Maturation2

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Abstract
Neuroblastoma cells were obtained from 13 young children and cultured in vitro for periods of 1 week to over a year. All but one of the biopsies contained undifferentiated masses of immature neuroblasts resembling small lymphocytes. Culture in vitro of the neuroblastoma cells resulted in differentiation and maturation into more mature neural elements within 5 months. The morphologic evidence for maturation of the neuroblastoma cells included an increase in nuclear size, development of a single large nucleolus, accumulation of Nissl ribonucleic acid substance, the formation of neurofibrils, and hypertrophy of axons. Explantation of a more mature-appearing neuroblastoma resulted in the transformation of all the nerve cells into mature ganglion cells within 20 days. The studies in vitro suggest that neuroblastoma may be the result of a biochemical defect which would prevent maturation of the nerve cells or a tumor population whose progeny have the potentialities to differentiate and mature. The factors responsible for these phenomena in vitro are under investigation.