Non–fibro-adipogenic pericytes from human embryonic stem cells attenuate degeneration of the chronically injured mouse muscle

Mosich, Gina M.; Husman, Regina; Shah, Paras; Sharma, Abhinav K.; Rezzadeh, Kevin; Aderibigbe, Temidayo; Hu, Vivian; McClintick, Daniel J; Wu, Guangjie; Gatto, Jonathan D; Xi, Haibin; Péault, Bruno; Petrigliano, Frank A.; Dar, Ayelet

doi:10.1172/jci.insight.125334

Cited by 13 publications

(26 citation statements)

References 49 publications

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“…Infraspinatus and supraspinatus muscles were separately fixed in 4% formalin, embedded in paraffin and sectioned axially. Sections were stained with hematoxylin and eosin (H&E) for general tissue structure analysis, measurement of myofiber cross-section 20…”

Section: Histologymentioning

confidence: 99%

“…Experimental RC tears in rats and mice involving the transection of supraspinatus and infraspinatus tendons (TT) along with the suprascapular nerve (DN) have replicated the marked degenerative fibrosis and fat accumulation found in these patients 11–13 . The rodent model of massive RC tears has been used by researchers to study the pathological progression of the disease and to improve their understanding of the cellular response 13–15 to injury, the molecular pathways that are responsible for it 16–18 and test therapeutic approaches to attenuate the progression of muscle degeneration 19–23 …”

Section: Introductionmentioning

confidence: 99%

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Lateral to medial fibro‐adipogenic degeneration are greater in infraspinatus than supraspinatus following nerve and tendon injury of murine rotator cuff

McClintick

et al. 2020

Journal Orthopaedic Research

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Section: Histologymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Lateral to medial fibro‐adipogenic degeneration are greater in infraspinatus than supraspinatus following nerve and tendon injury of murine rotator cuff

McClintick

et al. 2020

Journal Orthopaedic Research

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“…Recent studies have implicated PDGFRα + FAPs in fibroadipogenesis following massive rotator cuff tears (20,(26)(27)(28)(29)(30)(31). Liu et al demonstrated significant co-localization of immunofluorescence signals from transgenic murine PDGFRα + cells and adipogenic markers including peroxisome proliferatoractivated receptor γ (PPARγ), adiponectin, and perilipin A following tendon transection plus denervation in a murine rotator cuff tear (RCT) model (20).…”

Section: Contribution Of Rc Faps To Fibro-adipogenesismentioning

confidence: 99%

Fibro-adipogenesis in Injured Rotator Cuff Muscle

Subhash

Davies

Gatto

et al. 2022

Curr. Tissue Microenviron. Rep.

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Purpose of Review Fibro-adipogenic progenitors were first characterized in 2010 and later found to contribute significantly to muscle regeneration and mediate degenerative changes in muscle following injury. These progenitors were also found to have an influence on the rotator cuff muscle’s response to chronic injury which is defined by fibrosis accompanied by massive fatty degeneration. The purpose of this review is to highlight progenitor cells, their contribution to fibro-adipogenesis in rotator cuff tissue, and the factors influencing fibro-adipogenesis in this tissue. Recent Findings Fibro-adipogenic progenitors are a key mediator of the fatty infiltration notably prevalent in rotator cuff injury. Relative to other muscle groups, the rotator cuff has relatively high rates of fibro-adipogenesis following massive chronic rotator cuff tears. This may be linked to the pre-injury density of fibro-adipogenic progenitors in muscle tissue affecting post-injury levels of fibro-adipogenesis. In addition, suprascapular nerve injury in rat models of rotator cuff tears has demonstrated worse, histologic, and biomechanical properties and lower healing rates of rotator cuff repairs. However, fatty infiltration in the rotator cuff following suprascapular nerve compression has been shown to be reversible following release of the nerve compression. Summary The fibro-adipogenic response to acute and chronic injury in rotator cuff tissue is determined by a complex array of factors including progenitor cell influence, transcriptional pathways, chronicity of the injury, anatomic location of injury, microenvironmental influences, and the severity of nerve involvement. Elucidating the complex interactions of these factors will provide potential targets for therapeutic intervention in vivo.

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“…130 Injection of human MSC-like pericytes into degenerating murine RC muscles (tenotomy and neurectomy) also attenuates the level of degeneration. 131 Furthermore, beneficial effects of MSC delivery through paracrine signaling have been documented in other types of skeletal muscle injuries, including crush trauma and volumetric muscle loss, [132][133][134][135][136][137] suggesting the clinical potential of MSC therapy in promoting muscle regeneration in multiple muscle-associated injury and disease contexts.…”

Section: Cell Therapymentioning

confidence: 99%

Cellular and molecular modulation of rotator cuff muscle pathophysiology

Huang

Galatz

et al. 2021

Journal Orthopaedic Research

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Rotator cuff (RC) tendon tears are common shoulder injuries that result in irreversible and persistent degeneration of the associated muscles, which is characterized by severe inflammation, atrophy, fibrosis, and fatty infiltration. Although RC muscle degeneration strongly dictates the overall clinical outcomes, strategies to stimulate RC muscle regeneration have largely been overlooked to date. In this review, we highlight the current understanding of the cellular processes that coordinate muscle regeneration, and the roles of muscle resident cells, including immune cells, fibroadipogenic progenitors, and muscle satellite cells in the pathophysiologic regulation of RC muscles following injury. This review also provides perspectives for potential therapies to alleviate the hallmarks of RC muscle degeneration to address current limitations in postsurgical recovery.

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Non–fibro-adipogenic pericytes from human embryonic stem cells attenuate degeneration of the chronically injured mouse muscle

Abstract: Conflict of interest: A patent application (30435.354-US-P2) has been filed by BP, FAP, and AD on a method for generation of therapeutic pericytes from human pluripotent stem cells.

Cited by 13 publications

References 49 publications

Lateral to medial fibro‐adipogenic degeneration are greater in infraspinatus than supraspinatus following nerve and tendon injury of murine rotator cuff

Lateral to medial fibro‐adipogenic degeneration are greater in infraspinatus than supraspinatus following nerve and tendon injury of murine rotator cuff

Fibro-adipogenesis in Injured Rotator Cuff Muscle

Cellular and molecular modulation of rotator cuff muscle pathophysiology

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