Human pericytes adopt myofibroblast properties in the microenvironment of the IPF lung

Sava, Paul; Ramanathan, Anand; Dobronyi, Amelia; Peng, Xueyan; Sun, Huanxing; Ledesma-Mendoza, Adrian; Herzog, Erica L.; Gonzalez, Anjelica L.

doi:10.1172/jci.insight.96352

Cited by 110 publications

(86 citation statements)

References 41 publications

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“…Arthrofibrosis is a pathologic inflammatory condition characterized by an increase in connective tissue proliferation around a synovial joint resulting in debilitating loss of motion . The suspected key effector cell in arthrofibrosis is the myofibroblast, which contributes to pathologic endothelial tissue remodeling via its contractile properties, stimulation of extracellular matrix (ECM) production, and amplified response to transforming growth factor‐β (TGF‐β) . Activation of the arthrofibrotic process is thought to occur secondary to enhanced myofibroblast expression of α‐smooth muscle actin (α‐SMA) which contributes to increased collagen production and abnormally stiffened ECM surrounding the joint capsule .…”

mentioning

confidence: 99%

Inhibition of COX‐2 Pathway as a Potential Prophylaxis Against Arthrofibrogenesis in a Rabbit Model of Joint Contracture

Salib

Reina

Trousdale

et al. 2019

Journal Orthopaedic Research

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Arthrofibrosis is a common complication following total knee arthroplasty caused by pathologic fibroblast activation and excessive collagen deposition around a synovial joint leading to debilitating loss of motion. Treatment options are limited because the pathologic mechanisms remain to be characterized. Dysregulation of the inflammatory cascade may lead to communication between myofibroblasts and immune cells triggering tissue metaplasia, and excessive collagen deposition described clinically as arthrofibrosis. We explored the novel use of celecoxib (selective cyclooxygenase-2 [COX-2] inhibitor) to disrupt the downstream effects of the post-traumatic inflammatory cascade and inhibit scar tissue formation in a validated rabbit model of arthrofibrosis combined with new parameters for quantifying the stiffness of the posterior capsule. Biomechanical and molecular analyses, of contracted rabbit knee posterior capsule tissue after COX-2 inhibition revealed increased maximal passive extension and down-regulation of collagen messenger RNA compared with controls. Histopathologic examination suggested a trend of decreased quantities of dense fibrous connective tissue with COX-2 inhibition. These data may suggest that inhibiting the inflammatory cascade could potentially reduce pathologic myofibroblast activation, thereby reducing scar tissue formation and increasing the range of motion in arthrofibrotic joints. Implementing a multi-modal pharmacologic approach may simultaneously target numerous cellular components contributing to the complex process of arthrofibrogenesis.

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mentioning

confidence: 99%

Inhibition of COX‐2 Pathway as a Potential Prophylaxis Against Arthrofibrogenesis in a Rabbit Model of Joint Contracture

Salib

Reina

Trousdale

et al. 2019

Journal Orthopaedic Research

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“…This proposed mechanism may also keep pericytes from detaching and migrating into the interstitium away from a growing vessel. While more studies will be necessary to better understand the existence of these and potentially other pericyte‐retention mechanisms, pericyte loss by detachment and interstitial migration has been described for numerous disease conditions . It will therefore be important to further elucidate this phenomenon in healthy and pathological conditions.…”

Section: Pericyte Involvement In Angiogenic Sproutingmentioning

confidence: 99%

“…Laminins, which can integrate within the Col‐IV scaffold, are also important elements of the vBM . In addition, both pericytes and endothelial cells can secrete distinct isoforms of these ECM proteins . Pericytes must also utilize a corresponding set of integrins such as the α2, αV, β1, and β3 subunits to facilitate their interaction with this pro‐migration vBM .…”

Section: Pericyte Involvement In Angiogenic Sproutingmentioning

confidence: 99%

“…While more studies will be necessary to better understand the existence of these and potentially other pericyte-retention mechanisms, pericyte loss by detachment and interstitial migration has been described for numerous disease conditions. 24,25,94,[115][116][117][118][119][120][121][122][123] It will therefore be (Figure 2 and Movie S1), it must adhere to and migrate along a permissive substrate, which might be the endothelial cell surface itself. Alternatively, pericytes may engage an intermediate form of the vBM that is being jointly produced by the endothelium and associated pericytes.…”

Section: Peric Y Te Involvement In Ang Iog Enic S Proutingmentioning

confidence: 99%

“…91,95,132 In addition, both pericytes and endothelial cells can secrete distinct isoforms of these ECM proteins. 50,94,120 Pericytes must also utilize a corresponding set of integrins such as the α2, αV, β1, and β3 subunits to facilitate their interaction with this pro-migration vBM. 50,[133][134][135] As vessel formation progresses, pericytes synthesize and deposit an additional, and likely molecularly distinct, "outer layer" of the vBM that contributes to the eventual stabilization of nascent vessels (Figure 3).…”

Section: Peric Y Te Involvement In Ang Iog Enic S Proutingmentioning

confidence: 99%

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The pericyte microenvironment during vascular development

et al. 2019

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Vascular pericytes provide critical contributions to the formation and integrity of the blood vessel wall within the microcirculation. Pericytes maintain vascular stability and homeostasis by promoting endothelial cell junctions and depositing extracellular matrix (ECM) components within the vascular basement membrane, among other vital functions. As their importance in sustaining microvessel health within various tissues and organs continues to emerge, so does their role in a number of pathological conditions including cancer, diabetic retinopathy, and neurological disorders. Here, we review vascular pericyte contributions to the development and remodeling of the microcirculation, with a focus on the local microenvironment during these processes. We discuss observations of their earliest involvement in vascular development and essential cues for their recruitment to the remodeling endothelium. Pericyte involvement in the angiogenic sprouting context is also considered with specific attention to crosstalk with endothelial cells such as through signaling regulation and ECM deposition. We also address specific aspects of the collective cell migration and dynamic interactions between pericytes and endothelial cells during angiogenic sprouting. Lastly, we discuss pericyte contributions to mechanisms underlying the transition from active vessel remodeling to the maturation and quiescence phase of vascular development.

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Bioengineering and Clinical Translation of Human Lung and its Components

et al. 2023

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Clinical lung transplantation has rapidly established itself as the gold standard of treatment for end‐stage lung diseases in a restricted group of patients since the first successful lung transplant occurred. Although significant progress has been made in lung transplantation, there are still numerous obstacles on the path to clinical success. The development of bioartificial lung grafts using patient‐derived cells may serve as an alternative treatment modality; however, challenges include developing appropriate scaffold materials, advanced culture strategies for lung‐specific multiple cell populations, and fully matured constructs to ensure increased transplant lifetime following implantation. This review highlights the development of tissue‐engineered tracheal and lung equivalents over the past two decades, key problems in lung transplantation in a clinical environment, the advancements made in scaffolds, bioprinting technologies, bioreactors, organoids, and organ‐on‐a‐chip technologies. The review aims to fill the lacuna in existing literature toward a holistic bioartificial lung tissue, including trachea, capillaries, airways, bifurcating bronchioles, lung disease models, and their clinical translation. Herein, the efforts are on bridging the application of lung tissue engineering methods in a clinical environment as it is thought that tissue engineering holds enormous promise for overcoming the challenges associated with the clinical translation of bioengineered human lung and its components.

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Human pericytes adopt myofibroblast properties in the microenvironment of the IPF lung

Cited by 110 publications

References 41 publications

Inhibition of COX‐2 Pathway as a Potential Prophylaxis Against Arthrofibrogenesis in a Rabbit Model of Joint Contracture

Inhibition of COX‐2 Pathway as a Potential Prophylaxis Against Arthrofibrogenesis in a Rabbit Model of Joint Contracture

The pericyte microenvironment during vascular development

Bioengineering and Clinical Translation of Human Lung and its Components

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