Evolution and new frontiers of histology in bio‐medical research

Abstract

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.

Microscopic examination of spatial transcriptome using Seq-Scope

“…The development of light and electron microscopes profoundly contributed to the development of modern histology (Mazzarini et al, 2021). Protein and mRNA detection techniques, such as immunohistochemistry and RNA in situ hybridization, further allowed for examining specific biomolecules in histological slides (Callea et al, 1992).…”

Neurons: The Interplay between Cytoskeleton, Ion Channels/Transporters and Mitochondria

“…However, light microscopy did not allow an in-depth analysis of the cytoskeleton due to the intrinsic physical limitation related to the diffraction limit (200 nm). A fundamental turning point in the description and comprehension of cytoskeleton structures was represented by the availability of transmission electron microscopy (TEM) [ 76 ]. Since it uses electrons, rather than light, TEM can overcome the diffraction limit, thus allowing the actual description of neurofilaments and microtubules.…”

‘A picture is worth a thousand words’: The use of microscopy for imaging neuroinflammation

“…Despite the ease of use and wide applications of histological stains, their specificity is limited. The ability to target a protein of interest with a labeled antibody allowed the development of new techniques such as IHC and IF and opened up the neuroscience field [117]. The main techniques used for imaging neuroinflammation will be elucidated below, from immunohistochemical to in vivo approaches (Table 2 describes the advantages and limitations of basic types of preparation used to view specimens with a light microscope).…”