Delivery of monocyte lineage cells in a biomimetic scaffold enhances tissue repair

Hu, Michael S.; Walmsley, Graham G.; Barnes, Leandra A.; Weiskopf, Kipp; Rennert, Robert C.; Duscher, Dominik; Januszyk, Michael; Maan, Zeshaan N.; Hong, Wan Xing; Cheung, Alexander; Leavitt, Tripp; Marshall, Clement D.; Ransom, Ryan C.; Malhotra, Samir; Moore, Alessandra L.; Jayakumar, R.; Lorenz, H. Peter; Weissman, Irving L.; Gurtner, Geoffrey C.; Longaker, Michael T.

doi:10.1172/jci.insight.96260

Cited by 56 publications

(49 citation statements)

References 19 publications

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“…Boosting the signals that stimulate healing within the local microenvironment has been explored by using topical administration of certain growth factors and chemokines alone or coupled to different biomaterials ( 18 , 27 – 30 ). In preclinical models, local overexpression or administration of chemokine-loaded hydrogels (CXCL12 or CCL2) have been reported to improve wound healing ( 18 , 28 , 30 , 31 ), and CXCR2 −/− mice were shown to exhibit impaired healing ( 32 ). Despite promising experimental effects, clinical translation is hampered at least in part by high levels of proteolytic enzymes within the wound ( 33 ), which limits protein bioavailability.…”

Section: Discussionmentioning

confidence: 99%

Accelerated wound healing in mice by on-site production and delivery of CXCL12 by transformed lactic acid bacteria

Vågesjö

Öhnstedt

Mortier

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

110

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SignificanceChronic wounds comprise a growing clinical problem that represents >3% of the health care budget in industrialized countries. Drug development is hampered by the proteolytic nature of the wounds, which greatly limits drug bioavailability. Here, we present a technology that circumvents this by on-site production and reduced chemokine degradation. Lactobacilli bacteria were transformed into CXCL12-producing vectors to bioengineer the wound microenvironment after topical application. Consequently, the immune cells driving the healing process were reinforced, which greatly accelerated wound closure in healthy mice, in mouse models of hyperglycemia and peripheral ischemia, and in a wound model using human skin disks. Initial safety studies demonstrated that neither bacteria nor the chemokine produced was detected in systemic circulation following application to open wounds.

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Section: Discussionmentioning

confidence: 99%

Accelerated wound healing in mice by on-site production and delivery of CXCL12 by transformed lactic acid bacteria

Vågesjö

Öhnstedt

Mortier

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

110

View full text Add to dashboard Cite

show abstract

“…Chronic wounds in diabetic models show an attenuated recruitment of anti-inflammatory macrophages, diminished levels of TGF-b1, and a distinct cytokine and chemokine profile compared with normal wounds (Bekeschus et al, 2017;Okizaki et al, 2015). A recent study showed that injecting supraphysiologic levels of murine macrophages accelerated wound healing in diabetic mice (Hu et al, 2017). Monocytes derived from diabetic patients initiated a similar response.…”

Section: Discussionmentioning

confidence: 99%

Macrophages Promote Wound-Induced Hair Follicle Regeneration in a CX3CR1- and TGF-β1–Dependent Manner

Rahmani

Liu

Rosin

et al. 2018

Journal of Investigative Dermatology

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Hair follicle stem cells are regulated by intrafollicular and extrafollicular niche signals. Appropriate hair follicle regeneration relies on the coordinated release and integration of these signals. How immune cells, particularly cutaneous macrophages, influence the hair follicle stem cell niche and regeneration is not well understood. We took advantage of wound-induced hair growth (WIHG) to explore the relationship between wound macrophages and hair follicle regeneration. First, we showed that WIHG is dependent on CD11bF4/80 macrophages at 7-11 days after injury. Next, using CXCR1:CCR2 mice to capture the dynamic spectrum of macrophage phenotypes during wound healing, we showed that wound macrophages transition from a CXCR1 to a CXCR1 phenotype at the onset of WIHG. Finally, WIHG is abolished in mice deficient for CXCR1, delayed with pharmacological inhibition of transforming growth factor-β receptor type 1, and rescued with exogenous transforming growth factor-β1. Overall, we propose a model in which transforming growth factor-β1 and CXCR1 are critical for recruiting and maintaining the CCR2CXCR1Ly6CTNFα macrophages critical for stimulating WIHG.

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“…Inflammatory phase is essential during the first days. A study has been shown that administration of monocyte/macrophage could promote wound healing . In contrast, prolonged inflammatory phase delays proliferative process.…”

Section: Discussionmentioning

confidence: 99%

Topical application of Cinnamon verum essential oil accelerates infected wound healing process by increasing tissue antioxidant capacity and keratin biosynthesis

Ahmadi

Farahpour

Hamishehkar

2019

The Kaohsiung J of Med Scie

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Cinnamon essential oil is known to have antioxidant and antibacterial properties, which may accelerate, wound healing. This study was conducted to evaluate the effects of an ointment prepared from Cinnamon verum essential oil (C verum) in infected wound model. An experimentally excisional infected wound model was induced in mice. Circular excisional wound model of 5 mm surface area was surgically created and inoculated with 10 7 CFU of each of two bacterial strains of Staphylococcus aureus and Pseudomonas aeruginosa. The animals were divided into three groups and topically treated with soft yellow paraffin (control) and ointments containing 2% and 4% C verum. The mRNA levels of insulin-like growth factor I (IGF-1), fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF), epidermal keratin, fibroblasts, fibrocytes, immune cells, and vascular distribution as well as epithelialization ratio were investigated in order to evaluate the effects of C verum on wound healing. Tissue total antioxidant capacity and malondialdehyde levels (MDA) were also evaluated. Topical administration of C verum remarkably shortened the inflammatory phase, increased fibroblast distribution, collagen deposition, and accelerated the cellular proliferation, reepithelialization and keratin synthesis. The mRNA levels of IGF-1, FGF-2 and VEGF were remarkably higher in C verum-treated groups (especially 2%) in comparison control group. Topical administration of C verum increased antioxidant power and reduced MDA content in comparison to control animals. C verum accelerates wound healing by upregulating the IGF-1, FGF-2, and VEGF expression and increasing cell proliferation, collagen synthesis, and reepithelialization ratio.

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Delivery of monocyte lineage cells in a biomimetic scaffold enhances tissue repair

Cited by 56 publications

References 19 publications

Accelerated wound healing in mice by on-site production and delivery of CXCL12 by transformed lactic acid bacteria

Accelerated wound healing in mice by on-site production and delivery of CXCL12 by transformed lactic acid bacteria

Macrophages Promote Wound-Induced Hair Follicle Regeneration in a CX3CR1- and TGF-β1–Dependent Manner

Topical application of Cinnamon verum essential oil accelerates infected wound healing process by increasing tissue antioxidant capacity and keratin biosynthesis

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