Abstract
Tendon disorders represent a very common pathology in today’s population, and tendinopathies that account 30% of tendon-related injuries, affect yearly millions of people which in turn cause huge socioeconomic and health repercussions worldwide. Inflammation plays a prominent role in the development of tendon pathologies, and advances in understanding the underlying mechanisms during the inflammatory state have provided additional insights into its potential role in tendon disorders. Different cell compartments, in combination with secreted immune modulators, have shown to control and modulate the inflammatory response during tendinopathies. Stromal compartment represented by tenocytes has shown to display an important role in orchestrating the inflammatory response during tendon injuries due to the interplay they exhibit with the immune-sensing and infiltrating compartments, which belong to resident and recruited immune cells. The use of stem cells or their derived secretomes within the regenerative medicine field might represent synergic new therapeutical approaches that can be used to tune the reaction of immune cells within the damaged tissues. To this end, promising opportunities are headed to the stimulation of macrophages polarization towards anti-inflammatory phenotype together with the recruitment of stem cells, that possess immunomodulatory properties, able to infiltrate within the damaged tissues and improve tendinopathies resolution. Indeed, the comprehension of the interactions between tenocytes or stem cells with the immune cells might considerably modulate the immune reaction solving hence the inflammatory response and preventing fibrotic tissue formation. The purpose of this review is to compare the roles of distinct cell compartments during tendon homeostasis and injury. Furthermore, the role of immune cells in this field, as well as their interactions with stem cells and tenocytes during tendon regeneration, will be discussed to gain insights into new ways for dealing with tendinopathies.
Highlights
Tendons are strands of fibrous connective tissues with a great tensile strength that connect muscles to bones and allow force transfer [1]
Advances in understanding the inflammation’s underlying the cellular mechanisms and the molecular pathways involved have given more insights into tendon illness, as well as the circumstances that may aggravate it, but this information could lead to the development of new therapeutical approaches to be applied for tendinopathies
The application of stem cells or their derived secretomes has shown a great potential in improving tendon regeneration allowing to hypothesize the development of cell-based and cell-free strategies to modulate the immune response in tendon injuries
Summary
Tendons are strands of fibrous connective tissues with a great tensile strength that connect muscles to bones and allow force transfer [1]. Spontaneous adult tendon repair leads to scar tissue and fibrosis affecting the functionality of a tendon in terms of movement and strength [7] Adhesion process represents another frequent complication that might occur in tendon lesions. To efficaciously reach this target, it is crucial to understand how the interactions between immune cells and stem cells would impact subsequent host responses According to these premises, this review aims to compare the role of different tendon cell compartments in tendon homeostasis and during tendon injuries. Tendon Structure and Homeostasis Tendon by its nature is exposed to many mechanical loads throughout the whole life It is characterized by a hierarchical and anisotropic structure, which allows the tendon to perform its mechanical function without breaking down. Immune-sensing, and infiltrating compartments represent three different cell compartments that contribute each to a complex milieu of tendon homeostasis (Figure 1A) [3]
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