Stimulation of Skin Repair Is Dependent on Fibroblast Source and Presence of Extracellular Matrix

Wang, Hongjun; Pieper, Jeroen; Schotel, Roka; Blitterswijk, Clemens A. van; Lamme, Evert N.

doi:10.1089/ten.2004.10.1054

Cited by 49 publications

(35 citation statements)

References 44 publications

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“…Macrophages play a vital role during wound healing, and during L. major infection, they serve as both the host cell and the destroying effector cell for L. major (15,23). Moreover, during wound healing, macrophages secrete factors important for wound closure, fibroblast recruitment and activation, and collagen deposition/organization (11,33,36). Thus, to identify candidate genes involved in the differential wound healing and L. major disease phenotype observed between congenic and parental mice, we performed a microarray analysis of in vitro-infected and uninfected bone marrow-derived macrophages from Bc, B6, and C.B6-(lmr1, lmr2) mice (GEO accession number GSE17550).…”

Section: Resultsmentioning

confidence: 99%

Fine Mapping of Leishmania major Susceptibility Locus lmr2 and Evidence of a Role for Fli1 in Disease and Wound Healing

et al. 2010

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Genetic linkage studies of the host response to Leishmania major, the causative agent of cutaneous leishmaniasis, have identified significant genetic complexity in humans and mice. In the mouse model, multiple loci have been implicated in susceptibility to infection, but to date, the genes underlying these loci have not been identified. We now describe the contribution of a novel candidate gene, Fli1, to both L. major resistance and enhanced wound healing. We have previously mapped the L. major response locus, lmr2, to proximal chromosome 9 in a genetic cross between the resistant C57BL/6 strain and the susceptible BALB/c strain. We now show that the presence of the resistant C57BL/6 lmr2 allele in susceptible BALB/c mice confers an enhanced L. major resistance and wound healing phenotype. Fine mapping of the lmr2 locus permitted the localization of the lmr2 quantitative trait locus to a 5-Mb interval comprising 21 genes, of which microarray analysis was able to identify differential expression in 1 geneFli1. Analysis of Fli1 expression in wounded and L. major-infected skin and naïve and infected lymph nodes validated the importance of Fli1 in lesion resolution and wound healing and identified 3 polymorphisms in the Fli1 promoter, among which a GA repeat element may be the important contributor.Cutaneous leishmaniasis (CL) caused by the intracellular protozoan Leishmania major is a parasitic disease transmitted by blood-sucking sandflies. Skin macrophages are infected, and a skin lesion or granuloma develops at the site of infection (31). The severity of human CL varies, with phenotypes ranging from self-healing lesions to persistent lesions lasting years and leading to systemic disease (1). The severity of disease depends on the host's ability to form protective granulomas; in their absence, the parasites spread, resulting in diffuse cutaneous leishmaniasis. Studies of CL in mice have been of immense interest because they allow extensive experimental manipulation and reproduce many of the features of the human disease. To identify factors that modulate lesion resolution in infected individuals, we conducted genetic studies on two inbred mouse strains, C57BL/6 (B6) and BALB/c (Bc), that differ in their susceptibility to L. major. Resistance to L. major, epitomized by B6 mice, is characterized by the rapid healing of skin lesions, while the susceptibility in Bc mice is characterized by lesion chronicity and progression and systemic spread of the parasites.We previously identified three loci (lmr1, lmr2, and lmr3) mediating lesion resolution during L. major infection (28, 29). Mice congenic for all three resistant lmr alleles [strain C.B6-(lmr1, lmr2)] were generated on the susceptible Bc background and were shown to be more resistant to L. major and more able to heal noninfectious wounds than Bc mice, exhibiting a statistically significant tendency toward the phenotype of the donor strain B6. Furthermore, resistance to L. major was independent of T helper cell responses (12,13,30). The conclusions from these stud...

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Section: Resultsmentioning

confidence: 99%

Fine Mapping of Leishmania major Susceptibility Locus lmr2 and Evidence of a Role for Fli1 in Disease and Wound Healing

et al. 2010

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“…Although the inhibition of ECM synthesis is desired in the treatment of fibrotic diseases, there are also numerous situations in which drugs capable of increasing ECM production are useful. These situations include degenerative diseases of intervertebral disc and articular cartilage, impaired wound healing, and nerve basement membrane regeneration (Wang et al, 2004;Roughley et al, 2006;Armstrong et al, 2007). Nutraceuticals, in particular glucosamine, have been used as a treatment option in degenerative diseases of cartilage.…”

Section: A Targeting the Synthesis Of The Extracellular Matrixmentioning

confidence: 99%

Extracellular Matrix Molecules: Potential Targets in Pharmacotherapy

et al. 2009

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“…Both cell types possess multipotentiality [28,29,30], as they differentiate in culture or after implantation in vivo into osteoblasts [31,32], chondrocytes [33,34], adipocytes [35], myotubes [36,37], and neuronal cells [38,39]. Several reports indicate that the transplantation of ADSC-cultured constructs into athymic mice stimulates angiogenesis, wound repair, and re-epithelialization significantly better, when compared with fibroblast-cultured constructs [9,40,41]. Thus, the use of ADSCs and BMSCs is a promising tissue engineering strategy.…”

Section: Biomedical Applications Of Low Molecular Weight Heparin/pmentioning

confidence: 99%

Biomedical Application of Low Molecular Weight Heparin/Protamine Nano/Micro Particles as Cell- and Growth Factor-Carriers and Coating Matrix

Kishimoto

Takikawa

Hattori

et al. 2015

IJMS

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Low molecular weight heparin (LMWH)/protamine (P) nano/micro particles (N/MPs) (LMWH/P N/MPs) were applied as carriers for heparin-binding growth factors (GFs) and for adhesive cells including adipose-derived stromal cells (ADSCs) and bone marrow-derived mesenchymal stem cells (BMSCs). A mixture of LMWH and P yields a dispersion of N/MPs (100 nm–3 μm in diameter). LMWH/P N/MPs can be immobilized onto cell surfaces or extracellular matrix, control the release, activate GFs and protect various GFs. Furthermore, LMWH/P N/MPs can also bind to adhesive cell surfaces, inducing cells and LMWH/P N/MPs-aggregate formation. Those aggregates substantially promoted cellular viability, and induced vascularization and fibrous tissue formation in vivo. The LMWH/P N/MPs, in combination with ADSCs or BMSCs, are effective cell-carriers and are potential promising novel therapeutic agents for inducing vascularization and fibrous tissue formation in ischemic disease by transplantation of the ADSCs and LMWH/P N/MPs-aggregates. LMWH/P N/MPs can also bind to tissue culture plates and adsorb exogenous GFs or GFs from those cells. The LMWH/P N/MPs-coated matrix in the presence of GFs may provide novel biomaterials that can control cellular activity such as growth and differentiation. Furthermore, three-dimensional (3D) cultures of cells including ADSCs and BMSCs using plasma-medium gel with LMWH/P N/MPs exhibited efficient cell proliferation. Thus, LMWH/P N/MPs are an adequate carrier both for GFs and for stromal cells such as ADSCs and BMSCs, and are a functional coating matrix for their cultures.

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Stimulation of Skin Repair Is Dependent on Fibroblast Source and Presence of Extracellular Matrix

Cited by 49 publications

References 44 publications

Fine Mapping of Leishmania major Susceptibility Locus lmr2 and Evidence of a Role for Fli1 in Disease and Wound Healing

Fine Mapping of Leishmania major Susceptibility Locus lmr2 and Evidence of a Role for Fli1 in Disease and Wound Healing

Extracellular Matrix Molecules: Potential Targets in Pharmacotherapy

Biomedical Application of Low Molecular Weight Heparin/Protamine Nano/Micro Particles as Cell- and Growth Factor-Carriers and Coating Matrix

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