A Three-Dimensional Micro-Organ Culture System for Microtumor Spheroids from Human Malignant Glioma Specimens

Abstract

Tumor.tissue obtained from seven human malignant gliomas was minced and explanted into agarose-coated culture plates. After five to seven days, these microtumor fragments emerged as spheroids in four tumors and were maintained as multicellular organotypic spheroids for more than eight weeks. The morphological features and growth characteristics of different spheroids were studied and compared with the histology of the original tumor specimens. Light microscopic and ultrastructural studies of the spheroids demonstrated that morphological structures were similar to those of the original tumor tissue in vivo. The microtumor spheroids contained connective tissue, blood vessels, and macrophages, maintaining a three dimensional-architectural resemblance to the original tumors. Volumetric measurement of the spheroids showed that the size decreased initially and did not change thereafter over a period of time. This growth pattern of the spheroids was consistent with that of tumors in vivo, suggesting the linkage of cell proliferation and loss. This in vitro culture system for surgically removed brain tumor specimens may serve as an alternative to the in vivo xenograft model for the research of brain tumor biology, invasion and immunology and provide a valuable technique for the evaluation of new therapies, such as biologic response modifiers

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