Stereological methods in cell biology: where are we--where are we going?

The current state of the art in morphometric cell biology is reviewed by looking at the developmental state of stereological methods, and at the approaches used to arrive at quantitative structure-function correlation. Stereological methods have reached a fairly advanced level of sophistication since mathematical stereology has been developed as a branch of geometric probability theory. The application of these methods in cell biology lags behind, both quantitatively and qualitatively. Among the strategies used in exploiting stereological methods in cell biology the physiological approach (where a change is induced experimentally and its effect on the cells is followed by biochemical and morphometric methods) ranks highest and is still valid. More analytical approaches, such as combining stereology and biochemistry in cell fraction studies, are fraught with difficulties. In considering future developments of stereological methods, the emphasis will have to be 1) on developing procedures for eliminating biases such as section thickness or resolution effects, and 2) on increasing the efficiency of the methods by better sampling rules and improved instrumentation. The future trends in morphometric cell biology might best be served by exploiting the potentials of histochemistry and stereology by combining them with a view to 1) establishing procedures for cell-specific sampling and 2) developing methods towards "molecular morphometry" on the basis of immunocytochemical labeling.