Genome Editing of Mouse Fibroblasts by Homologous Recombination for Sustained Secretion of PDGF-B and Augmentation of Wound Healing

Barker, Jenny C.; Barker, A. D.; Bills, Jessica D.; Huang, Jingjing; Wight-Carter, Mary; Delgado, Imelda; Noble, Debby L.; Huang, Lily; Porteus, Matthew H.; Davis, Katie Ellen

doi:10.1097/prs.0000000000000427

Cited by 14 publications

(14 citation statements)

References 52 publications

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“…11,12 PDGF-B has been widely used for injury healing augmentation as a result of its biological effect. 13 During the current study, PDGF-B overexpression was demonstrated to accentuate the positive effect exerted by BMSCs on TB healing in a rotator cuff repair rat model.…”

mentioning

confidence: 67%

Retracted: Platelet‐derived growth factor subunit B is required for tendon‐bone healing using bone marrow–derived mesenchymal stem cells after rotator cuff repair in rats

Wang

Yin

Chu

et al. 2017

J of Cellular Biochemistry

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As a common cause of shoulder pain and disability, rotator cuff injury (RCI) represents a debilitating condition affecting an individual's quality of life. Although surgical repair has been shown to be somewhat effective, many patients may still suffer from reduced shoulder function. The aim of the current study was to identify a more effective mode of RCI treatment by investigating the effect of platelet-derived growth factor subunit B (PDGF-B) on tendon-bone healing after RCI repair by modifying bone marrow-derived mesenchymal stem cells (BMSCs). Surface markers of BMSCs were initially detected by means of flow cytometry, followed by establishment of the rat models and construction of the lentiviral vector. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, Thiazolyl Blue Tetrazolium Bromide (MTT) assay, alizarin red staining, and oil red O staining were used to provide verification that PDGF-B was indeed capable of promoting BMSC viability, osteogenic and adipogenic differentiation capability. Furthermore, biomechanical assessment results indicated that PDGF-B could increase the ultimate load and stiffness of the tendon tissue. Real-time reverse-transcription quantitative polymerase chain reaction and Western blot analysis methods provided evidence suggesting that PDGF-B facilitated the expression of tendon-bone healing-related genes and proteins, while contrasting results were obtained after PDGF-B silencing. Taken together, the key findings of the current study provided evidence suggesting that overexpressed PDGF-B could act to enhance tendon-bone healing after RCI repair, thus highlighting the potential of the functional promotion of PDGF-B as a future RCI therapeutic approach.

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mentioning

confidence: 67%

Retracted: Platelet‐derived growth factor subunit B is required for tendon‐bone healing using bone marrow–derived mesenchymal stem cells after rotator cuff repair in rats

Wang

Yin

Chu

et al. 2017

J of Cellular Biochemistry

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“…Previous work has shown that isolated dermal fibroblasts exhibit enhanced proliferation and migration in the presence of PDGF ligands. 8 – 10 After skin injury, application of PDGF accelerates the rate of skin wound closure, 11 – 13 and as such, has been utilized clinically for treatment of ulcerative wounds. 14 – 16 Conventional Pdgfrα null mice exhibit robust skin defects including dermal hypoplasia.…”

Section: Introductionmentioning

confidence: 99%

Platelet-derived growth factor signaling modulates adult hair follicle dermal stem cell maintenance and self-renewal

et al. 2017

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Hair follicle regeneration is dependent on reciprocal signaling between epithelial cells and underlying mesenchymal cells within the dermal papilla. Hair follicle dermal stem cells reside within the hair follicle mesenchyme, self-renew in vivo, and function to repopulate the dermal papilla and regenerate the connective tissue sheath with each hair cycle. The identity and temporal pattern of signals that regulate hair follicle dermal stem cell function are not known. Here, we show that platelet-derived growth factor signaling is crucial for hair follicle dermal stem cell function and platelet-derived growth factor deficiency results in a progressive depletion of the hair follicle dermal stem cell pool and their progeny. Using αSMACreER T2 :Rosa YFP :Pdgfrα flox mice, we ablated Pdgfrα specifically within the adult hair follicle dermal stem cell lineage. This led to significant loss of hair follicle dermal stem cell progeny in connective tissue sheath and dermal papilla of individual follicles, and a progressive reduction in total number of anagen hair follicles containing YFP+ve cells. As well, over successive hair cycles, fewer hair follicle dermal stem cells were retained within each telogen hair follicle suggesting an impact on hair follicle dermal stem cell self-renewal. To further assess this, we grew prospectively isolated hair follicle dermal stem cells (Sox2GFP+ve αSMAdsRed+ve) in the presence or absence of platelet-derived growth factor ligands. Platelet-derived growth factor-BB enhanced proliferation, increased the frequency of Sox2+ve hair follicle dermal stem cell progeny and improved inductive capacity of hair follicle dermal stem cells in an ex vivo hair follicle formation assay. Similar effects on proliferation were observed in adult human SKPs. Our findings impart novel insights into the signals that comprise the adult hair follicle dermal stem cell niche and suggest that platelet-derived growth factor signaling promotes self renewal, is essential to maintain the hair follicle dermal stem cell pool and ultimately their regenerative capacity within the hair follicle.

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“…The double-strand break was repaired by the mammalian cells' native DNA repair mechanism, viz., homologous recombination. These edited fibroblasts persisted in the wound bed for up to 5 months (106).…”

Section: Viral Vector-based Gene Delivery Systemsmentioning

confidence: 99%

Treating Polymicrobial Infections in Chronic Diabetic Wounds

2019

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SUMMARY This review provides a comprehensive summary of issues associated with treating polyclonal bacterial biofilms in chronic diabetic wounds. We use this as a foundation and discuss the alternatives to conventional antibiotics and the emerging need for suitable drug delivery systems. In recent years, extraordinary advances have been made in the field of nanoparticle synthesis and packaging. However, these systems have not been incorporated into the clinic for treatments other than for cancer or severe genetic diseases. We present a unifying perspective on how the field is evolving and the need for an early amalgamation of engineering principles and a biological understanding of underlying phenomena in order to develop a therapy that is translatable to the clinic in a shorter time.

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Genome Editing of Mouse Fibroblasts by Homologous Recombination for Sustained Secretion of PDGF-B and Augmentation of Wound Healing

Abstract: These data support that site-specific genome editing allows for sustained cell-based cytokine delivery. Furthermore, sustained release of PDGF-B increases the speed and quality of wound healing after a single application.

Cited by 14 publications

References 52 publications

Retracted: Platelet‐derived growth factor subunit B is required for tendon‐bone healing using bone marrow–derived mesenchymal stem cells after rotator cuff repair in rats

Retracted: Platelet‐derived growth factor subunit B is required for tendon‐bone healing using bone marrow–derived mesenchymal stem cells after rotator cuff repair in rats

Platelet-derived growth factor signaling modulates adult hair follicle dermal stem cell maintenance and self-renewal

Treating Polymicrobial Infections in Chronic Diabetic Wounds

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