Review of optical methods for noninvasive imaging of skin fibroblasts-From in vitro to ex vivo and in vivo visualization

Fibroblasts are among the most common cell types in the stroma responsible for creating and maintaining the structural organization of the extracellular matrix in the dermis, skin regeneration, and a range of immune responses. Until now, the processes of fibroblast adaptation and functioning in a varying environment have not been fully understood. Modern laser microscopes are capable of studying fibroblasts in vitro and ex vivo. One-photon- and two-photon-excited fluorescence microscopy, Raman spectroscopy/microspectroscopy are well-suited noninvasive optical methods for fibroblast imaging in vitro and ex vivo. In vivo staining-free fibroblast imaging is not still implemented. The exception is fibroblast imaging in tattooed skin. Although in vivo noninvasive staining-free imaging of fibroblasts in the skin has not yet been implemented, it is expected in the future. This review summarizes the state-of-the-art in fibroblast visualization using optical methods and discusses the advantages, limitations, and prospects for future noninvasive imaging. Currently, non-invasive imaging of dermal fibroblasts in vivo is only possible with TPE-FM and FLIM in tattooed skin. Other noninvasive optical methods have the potentialto visualize fibroblasts in vivo, but no relevant results have been presented sofar-only in vitro and ex vivo visualization using external staining dyes hasbeen reported.image