Abstract
In a worldwide effort to generate clinically useful therapeutic or preventive interventions, harnessing biophysical stimuli for directing cell fate is a powerful strategy. With the vision to control cell function through engineering cell shape, better understanding, measuring, and controlling cell shape for ultimately utilizing cell shape-instructive materials is an emerging “hot” topic in regenerative medicine. This review highlights how quantitation of cellular morphology is useful not only for understanding the effects of different microenvironmental or biophysical stimuli on cells, but also how it could be used as a predictive marker of biological responses, e.g., by predicting future mesenchymal stromal cell differentiation. We introduce how high throughput image analysis, combined with computational tools, are increasingly being used to efficiently and accurately recognize cells. Moreover, we discuss how a panel of quantitative shape descriptors may be useful for measuring specific aspects of cellular and nuclear morphology in cell culture and tissues. This review focuses on the mechano-biological principle(s) through which biophysical cues can affect cellular shape, and recent insights on how specific cellular “baseline shapes” can intentionally be engineered, using biophysical cues. Hence, this review hopes to reveal how measuring and controlling cellular shape may aid in future regenerative medicine applications.
Highlights
Worldwide, regenerative medicine works toward improving practical methods and experimental strategies to generate clinically useful therapeutic or preventive interventions
As this invited review was given the task to summarize topic-related advancements presented in the Tissue Engineering and Regenerative Medicine International Society (TERMIS) European Chapter Meeting 2017, this review focuses on cellular morphology as a novel assessment of biological responses and discusses broadly how biophysical cues affect cellular shape, how cellular shape can be measured quantitatively, and introduces the computational tools and approaches necessary for this task
As this review is in included in the TERMIS special issue: selected papers from TERMIS European Chapter Meeting 2017 on “Biomechanics, Morphology and Imaging”, we are highlighting some selected studies that were presented at this meeting that demonstrated the importance of measuring cell morphological features and their implications on tissue engineering
Summary
Regenerative medicine works toward improving practical methods and experimental strategies to generate clinically useful therapeutic or preventive interventions. After 16 h, the different g-levels led to cell and cytoskeleton morphology changes (an increase in cell area, actin stress fiber formation and intracellular anisotropy) that correlated with tenogenic differentiation markers, highlighting the importance of measuring cell shape and suggesting that exposure of musculoskeletal tissues to hypergravity may simulate loading and rescue the phenotype of degenerated tendon cells after exposure to near-weightlessness conditions The latter group’s work demonstrated that 3D printed scaffolds with different mechanical properties (compressive moduli), but with the same 3D microstructure resulted in elongated vs round and short cell morphologies [15]. A TERMIS 2017 keynote talk highlighted how spatially restricting macrophage spreading through micro-patterning, can prevent the activation of M0 macrophages into pro-inflammatory M1 macrophages and suggested that control of cell shape may be used to regulate the immune response [17] These recent results demonstrate the importance of measuring cell morphology in assessment of biological responses and in tissue engineering. Long-term phenotypic changes can transpire in the cell through comparable mechanisms
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