**1. Introduction**

Originally described as *time-lapse cinemicrography (microphotography)* [1], the modern *time-lapse microscopy* (TLM) emerged as a powerful and continuously improving tool for studying the cellular processes and cell-cell interactions with the applications ranging from fundamental aspects of molecular and cell biology to medical practice. The related *time-lapse photography* is more relevant to observing non-microscopic objects, such as plants and landscapes. TLM is the technique of capturing the sequence of microscopic images at regular intervals. TLM allows scientists to observe cellular dynamics and behavior of the population of living cells as well as of the single living cell within the population [2, 3]. Live cell imaging and the first nonsophisticated TLM techniques were pioneered at the very beginning of the twentieth century [4]. However, to be visible in the light microscope, the cells are to be subjected to fixation and staining, the processes that kill the cells. Introduction of phase-contrast microscopy in 1940s, development of fluorescent and multidimensional microscopy, flow cytometry and computational tools made live cell imaging a widespread approach and prompted scientists to consider TLM as an essential technique that carries an enormous promise for basic biological

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

science and medicine. For this review, we focused on mammalian cell cultures, although TLM can also be efficiently employed to study prokaryotic cells and unicellular microorganisms. In the absence of up-to-date comprehensive review on TLM advances, our aim was to familiarize the readers with the current advances of TLM methodology and provide for the reference guide to the most interesting reports where TLM has been utilized both for biological research and clinical purposes.

motility in fibroblastoid L929 cells [51]; human osteosarcoma MG-63 cells [52]; B35 neuroblastoma cells transiently expressing GFP and C6 glioma cells after staining with Hoechst 33258 [16] and motility of L5222 leukemia cells within the mesentery and migration of induced pluripotent cells during their early reprograming [53]. Of note, most studies are devoted to

Time-Lapse Microscopy

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TLM allows investigators to visualize and characterize *cell-cell contacts* [46, 52, 64–71]. The most interesting reports are concerned with the contacts between the various types of stem/ progenitor cells as well as the tumor-environment cell interactions: the importance of proper cell-cell contacts level for their correct positioning and cell polarity during organogenesis [39], glial-neuronal interactions [72–74], interactions between microglia and brain tumors [75], between astrocytes and neural progenitor cells [42], between mesenchymal stem cells and human myoblasts [76], dendritic cells [77], endothelial cells [78], cancer cells [79], extracellular matrix molecules [80], between erythroblastic islands in bone marrow [81], between neural progenitor cells [62, 82–84], between neural cells and hematopoietic stem cells that migrate to the central nervous system [85], hematopoietic stem cells and stromal cells [20], endothelial progenitor cells and cardiac myocytes [86], between induced pluripotent cells during the early reprogramming phase [53], vesicle traffic through intercellular bridges

*Cell division* and *cell death* can be well investigated with TLM [50, 52, 95–97]. Division and growth of both labeled [96, 98–100] and non-labeled [101, 102] cells in culture [52, 95, 98, 103–105] and tissue slices [106], including monitoring of a single cell [95, 99, 107–112], can be observed and assessed with TLM. The fluorescent ubiquitination-based cell cycle indicator (FUCCI) system can effectively label individual G1, S/G2/M and G1/S-transition phase nuclei as red, green and yellow, respectively, to visualize the real-time cell cycle transitions in living mammalian cells [113–116]. Microinjection of complementary RNA to cyclin B1 was reported as a tool for TLM studying meiosis [117]. Real-time imaging was employed to monitor nuclear envelope breakdown, which is one of the major morphological changes during mitosis [118] and apoptosis [119]; nucleolar assembly after mitosis [120]; tracking of template DNA strands during mitosis [121, 122]; preferred mitotic orientation of daughter cells, which is important for their following self-organization and tissue formation [123, 124]; interkinetic nuclear migration toward the apical surface in epithelial cells [125, 126]; multinucleation of skeletal muscle cells [12]; asymmetric division of stem cells [127–129]; identification and characterization of cell division genes by combining RNA interference, time-lapse microscopy and computational image processing [130]; cytokinesis [131, 132]; cleavage furrow [133]; abscission by using TLM in combination with electron microscopy [134, 135] and mitotic synchronization in the cell population [136]. The observations related to *cellular senescence* and various forms of *cell death* include re-entry into the cell cycle [10, 124, 137–139] and variable frequency of divisions [140]; changes in mitotic and interphase duration [141–147]; short G1 phase, which is a distinctive feature of mouse embryonic stem cells [148]; delayed G2 phase [149]; *neosis*, the term used for karyokinesis via nuclear budding followed by asymmetric, intracellular cytokinesis [150]; secretion of exosomes with anti-apoptotic microRNAs [151]; apoptosis [119, 152–156]; phagocytosis of apoptotic cells [157]; necrosis [158]; autophagy [159]; mitotic catastrophe [52, 143] and phototoxicity [160].

neural stem cells [18, 19, 54–63] due to growing clinical importance.

between prostate cancer cells [87] and synaptic contacts [88–94].
