CXCR4 Antagonist AMD3100 Accelerates Impaired Wound Healing in Diabetic Mice

Nishimura, Yukihide; Ii, Masaaki; Qin, Gangjian; Hamada, Hiromichi; Asai, Jun; Takenaka, Hideya; Sekiguchi, Hiroyuki; Renault, Marie-Ange; Jujo, Kentaro; Katoh, Norito; Kishimoto, Saburo; Ito, Aiko; Kamide, Christine; Kenny, John; Millay, Meredith; Misener, Sol; Thorne, Tina; Losordo, Douglas W.

doi:10.1038/jid.2011.356

Cited by 88 publications

(83 citation statements)

References 48 publications

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“…In the past, AMD3100, either by itself or in combination with platelet-derived growth factor or tacrolimus (Allen et al 2014;Lin et al 2014), improved wound healing and scar formation in diabetic mice (Nishimura et al 2011) and mice receiving thermal burns (Avniel et al 2005). Here we show that AMD3100 treatment promotes tissue regeneration and restores normal tissue structure and function after injury in a scarless manner.…”

Section: Discussionmentioning

confidence: 99%

A cellular, molecular, and pharmacological basis for appendage regeneration in mice

et al. 2015

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Regenerative medicine aims to restore normal tissue architecture and function. However, the basis of tissue regeneration in mammalian solid organs remains undefined. Remarkably, mice lacking p21 fully regenerate injured ears without discernable scarring. Here we show that, in wild-type mice following tissue injury, stromal-derived factor-1 (Sdf1) is up-regulated in the wound epidermis and recruits Cxcr4-expressing leukocytes to the injury site. In p21-deficient mice, Sdf1 up-regulation and the subsequent recruitment of Cxcr4-expressing leukocytes are significantly diminished, thereby permitting scarless appendage regeneration. Lineage tracing demonstrates that this regeneration derives from fate-restricted progenitor cells. Pharmacological or genetic disruption of Sdf1-Cxcr4 signaling enhances tissue repair, including full reconstitution of tissue architecture and all cell types. Our findings identify signaling and cellular mechanisms underlying appendage regeneration in mice and suggest new therapeutic approaches for regenerative medicine.

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Section: Discussionmentioning

confidence: 99%

A cellular, molecular, and pharmacological basis for appendage regeneration in mice

et al. 2015

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“…We review here the studies that have identified the molecular pathways regulating the translocation of c-kit-positive CPCs in view of the critical role that cell movement has in stem cell aging and the development of the cardiac senescent dysfunctional phenotype. Stromal cell-derived factor 1 (SDF-1), also known as C-X-C motif chemokine 12 (CXCL12), is a ubiquitously expressed cytokine, critically involved in the trafficking of hematopoietic (5,85,86,188,189) and nonhematopoietic (1,52,60,68,212,219,227,243,350) stem cells. Mice deficient for SDF-1 or its G-protein coupled receptor CXCR4 die perinatally due to defects in hematopoiesis, neurogenesis, vasculogenesis, and cardiogenesis (17,211,237,316,360).…”

Section: Cpc Mobilization In Response To Myocardial Injurymentioning

confidence: 99%

Aging Effects on Cardiac Progenitor Cell Physiology

Rota

Goichberg

Anversa

et al. 2015

Comprehensive Physiology

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Cardiac aging has been confounded by the concept that the heart is a postmitotic organ characterized by a predetermined number of myocytes, which is established at birth and largely preserved throughout life until death of the organ and organism. Based on this premise, the age of cardiac cells should coincide with that of the organism; at any given time, the heart would be composed of a homogeneous population of myocytes of identical age. The discovery that stem cells reside in the heart and generate cardiac cell lineages has imposed a reconsideration of the mechanisms implicated in the manifestations of the aging myopathy. The progressive alterations of terminally differentiated myocytes, and vascular smooth muscle cells and endothelial cells may represent an epiphenomenon dictated by aging effects on cardiac progenitor cells (CPCs). Changes in the properties of CPCs with time may involve loss of self-renewing capacity, increased symmetric division with formation of daughter committed cells, partial depletion of the primitive pool, biased differentiation to the fibroblast fate, impaired ability to migrate, and forced entry into an irreversible quiescent state. Telomere shortening is a major variable of cellular senescence and organ aging, and support the notion that CPCs with critically shortened or dysfunctional telomeres contribute to myocardial aging and chronic heart failure. These defects constitute the critical variables that define the aging myopathy in humans. Importantly, a compartment of functionally competent human CPCs persists in the decompensated heart pointing to stem cell therapy as a novel form of treatment for the aging myopathy.

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“…Another study found SDF-1 expression was increased in fibroblasts and blister fluid in burn wounds (Avniel et al, 2006). However, the role of SDF-1 in wound healing is not yet clear, and its role in keloids has not yet been investigated (Avniel et al, 2006;Gallagher et al, 2007;Nishimura et al, 2012;Sarkar et al, 2011).…”

Section: Introductionmentioning

confidence: 96%

TSLP Is a Potential Initiator of Collagen Synthesis and an Activator of CXCR4/SDF-1 Axis in Keloid Pathogenesis

Shin

Kim

et al. 2016

Journal of Investigative Dermatology

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Recently, thymic stromal lymphopoietin (TSLP), which is well studied in allergic diseases, has been reported in fibrotic diseases, including idiopathic pulmonary fibrosis and atopic dermatitis fibrosis. However, the role of TSLP in keloid is obscure. In this study, we assessed the expression of TSLP in keloid tissue and investigated the possible role of TSLP in keloid pathogenesis. We observed that TSLP expression was increased in keloid tissue compared to normal tissue. Furthermore, TSLP treatment induced increased collagen I and collagen III expression in fibroblasts via transforming growth factor-?; however, there was higher expression in keloid fibroblasts compared to normal fibroblasts. Stromal cell-derived factor-1?, which was recently reported to enhance wound healing through recruiting bone marrow-derived mesenchymal stem cells to the wound area, increased after TSLP treatment in fibroblasts and was primarily expressed in ?-smooth muscle action-positive myofibroblasts in keloid tissue. Furthermore, fibrocytes expressing CXCR4, a stromal cell-derived factor-1? receptor, were significantly increased in keloid tissue compared to normal tissue. Finally, intradermal TSLP injection on BALB/c mice increased stromal cell-derived factor-1? expression and CXCR4(+) fibrocytes infiltration. Our data suggest that TSLP is a potent inducer of collagen and transforming growth factor-? production in keloid fibroblasts. In addition, it might activate the CXCR4/stromal cell-derived factor-1 axis to increase fibrocyte infiltration into the keloid tissue.

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CXCR4 Antagonist AMD3100 Accelerates Impaired Wound Healing in Diabetic Mice

Cited by 88 publications

References 48 publications

A cellular, molecular, and pharmacological basis for appendage regeneration in mice

A cellular, molecular, and pharmacological basis for appendage regeneration in mice

Aging Effects on Cardiac Progenitor Cell Physiology

TSLP Is a Potential Initiator of Collagen Synthesis and an Activator of CXCR4/SDF-1 Axis in Keloid Pathogenesis

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