Topical application of laminin-332 to diabetic mouse wounds

Sullivan, Stephen R.; Underwood, Robert; Sigle, Randall O.; Fukano, Yuko; Muffley, Lara A.; Usui, Marcia L.; Gibran, Nicole S.; Antezana, Marcos A.; Carter, William G.; Olerud, John E.

doi:10.1016/j.jdermsci.2007.07.002

Cited by 14 publications

(12 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Both phenomena contributed to protracted re-epithelialization of COL7A1-deficient skin wounds, but aberrant laminin-332 organization is likely to be the main cause. Laminin-332 is commonly believed to be a promoter of epithelialization during wound healing (30)(31)(32), despite some controversy in the literature (33,34). Here, we found that irregular deposition of laminin-332 was associated with delayed migration of the epidermal tongues in the absence of COL7A1 in vivo, which indicates that not the sheer presence of laminin-332, but its assembly and deposition, play a functional role.…”

Section: Discussionmentioning

confidence: 57%

Collagen VII plays a dual role in wound healing

Nyström¹,

Velati²,

Mittapalli³

et al. 2013

J. Clin. Invest.

181

168

View full text Add to dashboard Cite

Although a host of intracellular signals is known to contribute to wound healing, the role of the cell microenvironment in tissue repair remains elusive. Here we employed 2 different mouse models of genetic skin fragility to assess the role of the basement membrane protein collagen VII (COL7A1) in wound healing. COL7A1 secures the attachment of the epidermis to the dermis, and its mutations cause a human skin fragility disorder coined recessive dystrophic epidermolysis bullosa (RDEB) that is associated with a constant wound burden. We show that COL7A1 is instrumental for skin wound closure by 2 interconnected mechanisms. First, COL7A1 was required for re-epithelialization through organization of laminin-332 at the dermal-epidermal junction. Its loss perturbs laminin-332 organization during wound healing, which in turn abrogates strictly polarized expression of integrin α6β4 in basal keratinocytes and negatively impacts the laminin-332/integrin α6β4 signaling axis guiding keratinocyte migration. Second, COL7A1 supported dermal fibroblast migration and regulates their cytokine production in the granulation tissue. These findings, which were validated in human wounds, identify COL7A1 as a critical player in physiological wound healing in humans and mice and may facilitate development of therapeutic strategies not only for RDEB, but also for other chronic wounds.

show abstract

Section: Discussionmentioning

confidence: 57%

Collagen VII plays a dual role in wound healing

Nyström¹,

Velati²,

Mittapalli³

et al. 2013

J. Clin. Invest.

181

168

View full text Add to dashboard Cite

show abstract

“…Wounds from individual mice were digitally photographed daily for 7 d. All photographs were taken from an angle perpendicular to the wound with a sterile ruler placed adjacent to the wounds for standardization (7). The wound area was quantified using NIH ImageJ software (NIH, Bethesda, MD, USA); and wound closure was expressed as the ratio of actual wound area to initial wound size.…”

Section: Quantification Of Wound Closurementioning

confidence: 99%

Activation of Poly(ADP-Ribose) Polymerase-1 Delays Wound Healing by Regulating Keratinocyte Migration and Production of Inflammatory Mediators

El-Hamoly

Hegedűs

Lakatos

et al. 2014

Mol Med

View full text Add to dashboard Cite

Poly(ADP-ribosyl)ation (PARylation) is a protein modification reaction regulating various diverse cellular functions ranging from metabolism, DNA repair and transcription to cell death. We set out to investigate the role of PARylation in wound healing, a highly complex process involving various cellular and humoral factors. We found that topically applied poly[ADP-ribose] polymerase (PARP) inhibitors 3-aminobenzamide and PJ-34 accelerated wound closure in a mouse model of excision wounding. Moreover, wounds also closed faster in PARP-1 knockout mice as compared with wild-type littermates. Immunofluorescent staining for poly(ADP-ribose) (PAR) indicated increased PAR synthesis in scattered cells of the wound bed. Expression of interleukin (IL)-6, tumor necrosis factor (TNF)-α, inducible nitric oxide synthase and matrix metalloproteinase-9 was lower in the wounds of PARP-1 knockout mice as compared with control, and expression of IL-1β, cyclooxygenase-2, TIMP-1 and -2 also were affected. The level of nitrotyrosine (a marker of nitrating stress) was lower in the wounds of PARP-1 knockout animals as compared with controls. In vitro scratch assays revealed significantly faster migration of keratinocytes treated with 3-aminobenzamide or PJ34 as compared with control cells. These data suggest that PARylation by PARP-1 slows down the wound healing process by increasing the production of inflammatory mediators and nitrating stress and by slowing the migration of keratinocytes.

show abstract

“…Extracellular matrix (ECM) is known to play a critical role in tissue repair, serving as a scaffold and as a modulator of cell function and growth factor functionality. 21,22 Cells cultured in adherent monolayers ultimately need to be lifted into suspension for further handling=manipulation, but this process disrupts any ECM milieu that may have been established. Therefore, we also hypothesize that ASCs prepared and delivered as 3D multicellular aggregates (MAs) will exhibit enhanced biological and therapeutic properties compared to cells prepared using traditional monolayer techniques and delivered as cell suspensions.…”

Section: Introductionmentioning

confidence: 99%

Human Adipose-Derived Stromal Cells Accelerate Diabetic Wound Healing: Impact of Cell Formulation and Delivery

Amos

Kapur

Stapor

et al. 2010

Tissue Engineering Part A

179

150

View full text Add to dashboard Cite

Human adipose-derived stromal cells (ASCs) have been shown to possess therapeutic potential in a variety of settings, including cutaneous wound healing; however, it is unknown whether the regenerative properties of this cell type can be applied to diabetic ulcers. ASCs collected from elective surgical procedures were used to treat fullthickness dermal wounds in leptin receptor-deficient (db=db) mice. Cells were delivered either as multicellular aggregates or as cell suspensions to determine the impact of cell formulation and delivery methods on biological activity and in vivo therapeutic effect. After treatment with ASCs that were formulated as multicellular aggregates, diabetic wounds experienced a significant increase in the rate of wound closure compared to wounds treated with an equal number of ASCs delivered in suspension. Analysis of culture supernatant and gene arrays indicated that ASCs formulated as three-dimensional aggregates produce significantly more extracellular matrix proteins (e.g., tenascin C, collagen VI a3, and fibronectin) and secreted soluble factors (e.g., hepatocyte growth factor, matrix metalloproteinase-2, and matrix metalloproteinase-14) compared to monolayer culture. From these results, it is clear that cell culture, formulation, and delivery method have a large impact on the in vitro and in vivo biology of ASCs.

show abstract

Topical application of laminin-332 to diabetic mouse wounds

Cited by 14 publications

References 47 publications

Collagen VII plays a dual role in wound healing

Collagen VII plays a dual role in wound healing

Activation of Poly(ADP-Ribose) Polymerase-1 Delays Wound Healing by Regulating Keratinocyte Migration and Production of Inflammatory Mediators

Human Adipose-Derived Stromal Cells Accelerate Diabetic Wound Healing: Impact of Cell Formulation and Delivery

Contact Info

Product

Resources

About