scholarly journals A dynamic spectrum of monocytes arising from the in situ reprogramming of CCR2+ monocytes at a site of sterile injury

2015 ◽  
Vol 212 (4) ◽  
pp. 447-456 ◽  
Author(s):  
Daniela Dal-Secco ◽  
Jing Wang ◽  
Zhutian Zeng ◽  
Elzbieta Kolaczkowska ◽  
Connie H.Y. Wong ◽  
...  
Keyword(s):  
Wound Healing ◽  
Tissue Repair ◽  
Hepatic Injury ◽  
Dynamic Spectrum ◽  
Fluorescent Reporters ◽  
Injured Area ◽  
A Site ◽  
Local Cytokine

Monocytes are recruited from the blood to sites of inflammation, where they contribute to wound healing and tissue repair. There are at least two subsets of monocytes: classical or proinflammatory (CCR2hiCX3CR1low) and nonclassical, patrolling, or alternative (CCR2lowCX3CR1hi) monocytes. Using spinning-disk confocal intravital microscopy and mice with fluorescent reporters for each of these subsets, we were able to track the dynamic spectrum of monocytes that enter a site of sterile hepatic injury in vivo. We observed that the CCR2hiCX3CR1low monocytes were recruited early and persisted for at least 48 h, forming a ringlike structure around the injured area. These monocytes transitioned, in situ, from CCR2hiCx3CR1low to CX3CR1hiCCR2low within the ringlike structure and then entered the injury site. This phenotypic conversion was essential for optimal repair. These results demonstrate a local, cytokine driven reprogramming of classic, proinflammatory monocytes into nonclassical or alternative monocytes to facilitate proper wound-healing.

CHANGES OF PER2 GENE KNOCKOUT ON TISSUE REPAIR: EPIDERMAL WOUND HEALING ASSAY IN VIVO

2020 ◽  
Vol 130 (3) ◽  
pp. e254
Author(s):  
VERONICA QUISPE YUJRA ◽  
ERICKA JANINE D. DA SILVEIRA ◽  
DANIEL ARAKI RIBEIRO ◽  
ROGERIO CASTILHOS ◽  
CRISTIANE SQUARIZE
Keyword(s):  
Wound Healing ◽  
Tissue Repair ◽  
Gene Knockout ◽  
Wound Healing Assay

scholarly journals Comparison of healing patterns of different side-cut angulations after FS-LASIK

2021 ◽  
Vol 14 (3) ◽  
pp. 430-435
Author(s):  
Wei Wei ◽  
◽  
Di Shen ◽  
Xiao-Rui Wang ◽  
Yu-Qiang Ji ◽  
...  
Keyword(s):  
Wound Healing ◽  
Femtosecond Laser ◽  
Nerve Regeneration ◽  
Anterior Segment ◽  
Higher Order ◽  
Laser In Situ Keratomileusis ◽  
Higher Order Aberrations ◽  
Corneal Confocal Microscopy

AIM: To investigate and evaluate healing patterns around flaps made with different side-cut angulations after femtosecond laser in situ keratomileusis (FS-LASIK). METHODS: Thirty-four patients (68 eyes) received a 90° side-cut (n=34) or a 120° side-cut flaps (n=34) made with a femtosecond laser. One day, 1wk, 1 and 3mo postoperatively, side-cut scar was evaluated under slit-lamp photography according to a new grading system (Grade 0=transparent scar, 1=faint healing opacity, and 2=evident healing opacity). In vivo corneal confocal microscopy and anterior segment optical coherence tomography (AS-OCT) were used to observe wound-healing patterns around flap margin in the two groups. Sirius Scheimpflug Analyzer was also used to analyze higher order aberrations 3mo after surgery. RESULTS: There were no significant differences in flap wound-healing patterns at each follow up between the two groups (P>0.05). Three months after surgery, the flap edge scar classified as Grade 0 had excellent apposition and rapid nerve regeneration. At 3 mm and 5 mm pupil diameters, there were significant differences in trefoil aberrations between the two groups (P<0.05), but no statistically significant differences were found in total higher order aberrations (HOAs), spherical aberrations or coma in any of the pupil size conditions (P>0.05). CONCLUSION: Flap edge scars classified as Grade 0 have excellent apposition and rapid nerve regeneration, and 120° side-cut angle flaps induce less trefoil aberrations after FS-LASIK.

scholarly journals In vivo sequestration of innate small molecules to promote bone healing

2019 ◽  
Author(s):  
Yuze Zeng ◽  
Yu-Ru V. Shih ◽  
Gurpreet S. Baht ◽  
Shyni Varghese
Keyword(s):  
Small Molecules ◽  
Human Body ◽  
Tissue Repair ◽  
Physiological Level ◽  
Extracellular Adenosine ◽  
Injury Site ◽  
Synthetic Biomaterial ◽  
Repair Mechanisms

AbstractApproaches that enable innate repair mechanisms hold great potential for tissue repair. Herein, we describe biomaterial-assisted sequestration of small molecules to localize pro-regenerative signaling at the injury site. Specifically, we designed a synthetic biomaterial containing boronate molecules to sequester adenosine, a small molecule ubiquitously present in the human body. The biomaterial-assisted sequestration of adenosine leverages the transient surge of extracellular adenosine following injury to prolong local adenosine signaling. We demonstrated that implantation of the biomaterial patch following injury establishes an in-situ stockpile of adenosine, resulting in accelerated healing by promoting both osteoblastogenesis and angiogenesis. The adenosine content within the patch recedes to the physiological level as the tissue regenerates. In addition to sequestering endogenous adenosine, the biomaterial is also able to deliver exogenous adenosine to the site of injury, offering a versatile solution to utilizing adenosine as a potential therapeutic for tissue repair.

scholarly journals Impact of MMP-2 and MMP-9 activation on wound healing, tumor growth and RACPP cleavage

2018 ◽  
Author(s):  
Dina V. Hingorani ◽  
Csilla N. Lippert ◽  
Jessica L. Crisp ◽  
Elamprakash N. Savariar ◽  
Jonathan P.C. Hasselmann ◽  
...  
Keyword(s):  
Wound Healing ◽  
Tumor Progression ◽  
Tumor Cells ◽  
Mammary Tumorigenesis ◽  
Cell Penetrating Peptides ◽  
Double Knockout ◽  
Mendelian Genetics ◽  
A Site

AbstractMatrix metalloproteinases-2 and -9 (MMP-2/-9) are key tissue remodeling enzymes that have multiple overlapping activities critical for wound healing and tumor progression in vivo. To overcome issues of redundancy, we created MMP-2/-9 double knockout (DKO) mice in the C57BL/6 background to examine wound healing. We then bred the DKO mice into the polyomavirus middle T (PyVmT) model of breast cancer to analyze the role of these enzymes in tumorigenesis. Breeding analyses indicated that significantly fewer DKO mice were born than predicted by Mendelian genetics and weaned DKO mice were growth compromised compared with wild type (WT) cohorts. Epithelial wound healing was dramatically delayed in adult DKO mice and when the DKO was combined with the PyVmT oncogene, we found that the biologically related process of mammary tumorigenesis was inhibited in a site-specific manner. To further examine the role of MMP-2/-9 in tumor progression, tumor cells derived from WT or DKO PyVmT transgenic tumors were grown in WT or DKO mice. Ratiometric activatable cell penetrating peptides (RACPPs) previously used to image cancer based on MMP-2/-9 activity were used to understand differences in MMP activity in WT or knockout syngeneic tumors in WT and KO animals. Analysis of an MMP-2 selective RACPP in WT or DKO mice bearing WT and DKO PyVmT tumor cells indicated that the genotype of the tumor cells was more important than the host stromal genotype in promoting MMP-2/-9 activity in the tumors in this model system. Additional complexities were revealed as the recruitment of host macrophages by the tumor cells was found to be the source of the tumor MMP-2/-9 activity and it is evident that MMP-2/-9 from both host and tumor is required for maximum signal using RACPP imaging for detection. We conclude that in the PyVmT model, the majority of MMP-2/-9 activity in mammary tumors is associated with host macrophages recruited into the tumor rather than that produced by the tumor cells themselves. Thus therapies that target tumor-associated macrophage functions have the potential to slow tumor progression.

Expression of integrin receptors and their role in adhesion, spreading and migration of normal human melanocytes

1993 ◽  
Vol 105 (1) ◽  
pp. 179-190 ◽  
Author(s):  
G. Zambruno ◽  
P.C. Marchisio ◽  
A. Melchiori ◽  
S. Bondanza ◽  
R. Cancedda ◽  
...  
Keyword(s):  
Wound Healing ◽  
Membrane Surface ◽  
Integrin Receptors ◽  
Human Melanocytes ◽  
Normal Human ◽  
And Migration ◽  
Alpha V Beta 3

Integrin receptors of human melanocytes in vivo and of melanocytes isolated and cultured from in vitro reconstituted normal human epidermis were investigated. Melanocytes were studied by high-resolution immunocytochemistry of in situ epidermis and were found to expose only the integrin subunits alpha 3, alpha 6, alpha v and beta 1 on their plasma membrane surface. Instead, cultured normal melanocytes expressed alpha 3 beta 1, alpha 5 beta 1, alpha 6 beta 1 and alpha v beta 3, which were immunoprecipitated from both metabolically and surface-labeled cells. Beta 1 integrins were diffused on the adhesion surface, while alpha v beta 3 was clustered in focal contacts both in control cells and upon dendrite induction with phorbol 12-myristate 13-acetate (PMA). The functional roles of integrins were studied in vitro by cell adhesion, spreading and migration assays. The sum of the data indicated that, in normal human melanocytes: (i) adhesion to defined substrata is mainly mediated by specific beta 1 integrins; (ii) spreading is mainly modulated by alpha v beta 3; (iii) the beta 1 and beta 3 heterodimers cooperate in regulating migration. The in vitro expression of two integrins (alpha v beta 3 and alpha 5 beta 1) that are not exposed in situ, and their role in the spreading and migratory properties of melanocytes, strongly suggest that they are involved in regenerating a normally pigmented epidermis during wound healing by controlling melanocyte spreading and migration over a provisional matrix. Tumor promoters, such as PMA, selectively increased the expression of alpha 3 beta 1. We suggest that this integrin might be involved in melanocyte migration on the newly formed basement membrane during wound healing as well as in intercellular recognition of adjacent keratinocytes.

Expression of the beta 6 integrin subunit in development, neoplasia and tissue repair suggests a role in epithelial remodeling

1995 ◽  
Vol 108 (6) ◽  
pp. 2241-2251 ◽  
Author(s):  
J.M. Breuss ◽  
J. Gallo ◽  
H.M. DeLisser ◽  
I.V. Klimanskaya ◽  
H.G. Folkesson ◽  
...  
Keyword(s):  
Wound Healing ◽  
Epithelial Cells ◽  
Lung Injury ◽  
Tissue Repair ◽  
Expression Patterns ◽  
Alveolar Epithelial Cells ◽  
Integrin Subunit ◽  
Fibronectin Receptor ◽  
High Level

The alpha v beta 6 integrin was identified in cultured epithelial cells and functions as a fibronectin receptor. We have now used monoclonal antibodies to determine in vivo expression patterns of the beta 6 subunit in normal and pathological human or primate tissues, and during experimental wound healing or induced lung injury. The results indicate that beta 6 expression is restricted to epithelia and is up-regulated in parallel with morphogenetic events, tumorigenesis, and epithelial repair. During development of the kidney, lung, and skin, we found that beta 6 is expressed by specific types of epithelial cells, whereas it is mostly undetectable in normal adult kidney, lung and skin. In contrast, we detected high-level expression in several types of carcinoma. For example, beta 6 is almost invariably neo-expressed in squamous cell carcinomas derived from the oral mucosa, often focally localized at the infiltrating edges of tumor islands. Expression of beta 6 is also upregulated in migrating keratinocytes at the wound edge during experimental epidermal wound healing. Similarly, beta 6 expression is induced in type II alveolar epithelial cells during lung injury caused by injection of live bacteria. We also observed beta 6 expression in adult lungs and kidneys at focal sites of subclinical inflammation, as well as in a variety of clinical specimens from patients with chronic or acute inflammation of the lungs or kidneys. From these findings and earlier results, we hypothesize that alpha v beta 6 affects cell spreading, migration and growth during reorganization of epithelia in development, tissue repair, and neoplasia.

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