Evolution and new frontiers of histology in bio‐medical research

Histology refers to the study of the morphology of cells within their natural tissue environment. As a bio‐medical discipline, it dates back to the development of first microscopes which allowed to override the physical visual limitation of the human eye. Since the first observations, it was understood that cell shape predicts function and, therefore, shape alterations can identify and explain dysfunction and diseases. The advancements in morphological investigation techniques have allowed to extend our understanding of the shape–function relationships close to the molecular level of organization of tissues, as well as to derive reliable data not only from fixed, and hence static, biological samples but also living cells and tissues and even for extended time periods. These modern approaches, which encompass quantitative microscopy, precision microscopy, and dynamic microscopy, represent the new frontier of morphology. This article summarizes how the microscopy techniques have evolved to properly face the challenges of biomedical sciences, thus transforming histology from a merely qualitative discipline, which played an ancillary role to traditional “major” sciences such as anatomy, to a modern experimental science capable of driving knowledge progress in biology and medicine. Since its origin, histology has evolved from a merely qualitative morphological discipline to a modern experimental science capable of yielding reliable morpho‐functional information extending close to the molecular level. The major advances of histology are parallel to those of digital imaging and computer technology, which allowed to obtain digitized images suitable for quantitative, precision, and time‐course analyses. After a historical excursus, this review describes the modern histological methodologies, such as quantitative, precision, and dynamic microscopy, and provides key examples of their use in bio‐medical research.