Macrophages and fibroblasts in foreign body reactions: How mechanical cues drive cell functions?

Li, Rihan; Feng, Dongdong; Han, Siyuan; Zhai, Xiaoyue; Yu, Xinmiao; Fu, Yuanyuan; Jin, Feng

doi:10.1016/j.mtbio.2023.100783

Cited by 7 publications

(1 citation statement)

References 158 publications

(197 reference statements)

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“…In contradistinction to several of these observations, it is interesting to note that a number of other studies have observed that stiff substrates appear to prime macrophages toward the M2 phenotype (summarized in [ 64 ]). It has been speculated that, in addition to contributions of the matrix proper, additional interfering factors, such as culture conditions and source, likely cause these conflicting results.…”

Section: Inflammation Phasementioning

confidence: 94%

Roles of Mechanosensitive Channel Piezo1 in Wound Healing and Scar Formation

Rennekampff,

Tenenhaus,

Rennekampff

et al. 2024

Life

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The ability to heal one’s wounds is perhaps one of the most fundamental and critical of physiologic processes. This coordinated and closely regulated sequential biological process involves a variety of migratory and resident cells. The activation, modulation, balance, and control of these functions depend upon soluble mediators that activate cells and modulate their diverse functions. Recent advances have identified mechanotransduction as functionally integral in many different cell types and physiologic processes. The mechanically sensitive ion channel Pieoz1 is expressed on platelets, neutrophils, macrophages, endothelial cells, keratinocytes, and fibroblasts, all of which are principally involved in wound healing. On a cellular level, there have been great advances in our understanding of the functional role of Piezo1 mechanotransduction in cutaneous wounding. The blocking of Piezo1 has recently been shown to reduce scarring in vivo and yet, thus far, a comprehensive understanding of the roles that Piezo1 plays in in vivo wound healing remains lacking. Recognizing the ever-present and critical importance of optimal and reparative wound healing, and with the availability of new physical mechanomodulating devices, the time is ripe for gaining deeper insights into optimizing wound healing. In this review, we describe the current knowledge of Piezo1 related to wound healing.

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Section: Inflammation Phasementioning

confidence: 94%

Roles of Mechanosensitive Channel Piezo1 in Wound Healing and Scar Formation

Rennekampff,

Tenenhaus,

Rennekampff

et al. 2024

Life

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Differential effects of macrophage subtype‐specific cytokines on fibroblast proliferation and endothelial cell function in co‐culture system

Isali,

McClellan,

Wong

et al. 2024

J Biomedical Materials Res

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Macrophages are involved in several critical activities associated with tissue repair and regeneration. Current approaches in regenerative medicine are focusing on leveraging the innate immune response to accelerate tissue regeneration and improve long‐term healing outcomes. Of particular interest in this regard are the currently known, four main M2 macrophage subtypes: M2interleukin (IL)‐4,IL‐13, M2IC, M2IL‐10, M2non‐selective adenosine receptor agonists (NECA) (M2IL‐4,IL‐13 → M2NECA). In this study, rat bone marrow‐derived macrophages (M0) were polarized to each of the four subtypes M2IL‐4,IL‐13 → M2NECA and cultured for 72 h in vitro. Luminex assay results highlighted increased production of tissue inhibitor of metalloproteinases‐1 (TIMP‐1) for M2IL‐4,IL‐13, higher amounts of transforming growth factor‐beta 1 (TGF‐β1) for M2IL‐10, and elevated vascular endothelial growth factor A (VEGF‐A) from M2NECA. Co‐culture experiments performed with M2IL‐10 macrophages and L929 fibroblasts highlighted the increased production of soluble collagen within the media as well as higher amounts of collagen in the extracellular matrix. Human umbilical vein endothelial cells (HUVECs) were co‐cultured with M2NECA macrophages, which demonstrated an increase in intercellular adhesion molecule (ICAM) and platelet endothelial cell adhesion molecule (PECAM), as well as increased formation of endothelial tubes. The findings of this study emphasize a critical demand for further characterization and analyses of distinct M2 subtypes and careful selection of specific macrophage populations for regeneration of specific tissue types. The current, broad classification of “M2” may be sufficient in many general tissue engineering applications, but, as conditions are constantly in flux within the microenvironment in vivo, a higher degree of specificity and control over the initial M2 subtype could result in more consistent long‐term outcomes where macrophages are utilized as part of an overall regenerative strategy.

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Pharmacological antagonism of Ccr2+ cell recruitment to facilitate regenerative tendon healing

Smolyak,

Rodenhouse,

Nichols

et al. 2024

Journal Orthopaedic Research

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Successful tendon healing requires sufficient deposition and remodeling of new extracellular matrix at the site of injury, with this process mediating in part through fibroblast activation via communication with macrophages. Moreover, resolution of healing requires clearance or reversion of activated cells, with chronic interactions with persistent macrophages impairing resolution and facilitating the conversion to fibrotic healing. As such, modulation of the macrophage environment represents an important translational target to improve the tendon healing process. Circulating monocytes are recruited to sites of tissue injury, including the tendon, via upregulation of cytokines including Ccl2, which facilitates recruitment of Ccr2+ macrophages to the healing tendon. Our prior work has demonstrated that Ccr2−/− can modulate fibroblast activation and myofibroblast differentiation. However, this approach lacked temporal control and resulted in healing impairments. Thus, in the current study we have leveraged a Ccr2 antagonist to blunt macrophage recruitment to the healing tendon in a time‐dependent manner. We first tested the effects of Ccr2 antagonism during the acute inflammatory phase and found that this had no effect on the healing process. In contrast, Ccr2 antagonism during the early proliferative/granulation tissue period resulted in significant improvements in mechanical properties of the healing tendon. Collectively, these data demonstrate the temporally distinct impacts of modulating Ccr2+ cell recruitment and Ccr2 antagonism during tendon healing and highlight the translational potential of transient Ccr2 antagonism to improve the tendon healing process.

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Macrophages and fibroblasts in foreign body reactions: How mechanical cues drive cell functions?

Cited by 7 publications

References 158 publications

Roles of Mechanosensitive Channel Piezo1 in Wound Healing and Scar Formation

Roles of Mechanosensitive Channel Piezo1 in Wound Healing and Scar Formation

Differential effects of macrophage subtype‐specific cytokines on fibroblast proliferation and endothelial cell function in co‐culture system

Pharmacological antagonism of Ccr2+ cell recruitment to facilitate regenerative tendon healing

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