Dedifferentiation and in vivo reprogramming of committed cells in wound repair (Review)

Abstract

Accumulating evidence has shown that cell dedifferentiation or reprogramming is a pivotal procedure for animals to deal with injury and promote endogenous tissue repair. Tissue damage is a critical factor that triggers cell dedifferentiation or reprogramming in vivo. By contrast, microenvironmental changes, including the loss of stem cells, hypoxia, cell senescence, inflammation and immunity, caused by tissue damage can return cells to an unstable state. If the wound persists in the long-term due to chronic damage, then dedifferentiation or reprogramming of the surrounding cells may lead to carcinogenesis. In recent years, extensive research has been performed investigating cell dedifferentiation or reprogramming in vivo, which can have significant implications for wound repair, treatment and prevention of cancer in the future. The current review summarizes the molecular events that are known to drive cell dedifferentiation directly following tissue injury and the effects of epigenetic modification on dedifferentiation or reprogramming in vivo. In addition, the present review explores the intracellular mechanism of endogenous tissue repair and its relationship with cancer, which is essential for balancing the risk between tissue repair and malignant transformation after injury.

The Goldilocks Zone of Healing An unexploited resource for advanced healing

“…Investigations on cell reprogramming have shown cell dedifferentiation or reprogramming as a key method for tissue repair after injury, where adequate control of the local microenvironment undoubtedly serves a crucial role. Even in mature tissues, the characteristics of differentiated cells are not irreversible and maintain a certain degree of plasticity, demonstrating that the ectopic expression of key transcription factors, microRNAs (miRNAs), or even treatment using suitable compounds, can be used to induce intercellular conversion (Guo, Wu, & Yang 2022). Following injury, when it is critical to quickly regenerate and restore tissue integrity and function, other types of cellular plasticity may become crucial for organismal survival.…”

Homeostasis and evolution in relation to regeneration and repair

“…After the start of regeneration or repair, acute hypoxia, glycolysis, inflammation, senescence and chromatin remodelling must be maintained at appropriate levels and withdrawn at appropriate times; otherwise, these conditions become cancer‐inducing factors, despite creating a relaxed environment for cells that promotes reprogramming and facilitates cell type conversion (Calcinotto et al., 2019; Guo et al., 2022).…”