Suppressive effects of induced pluripotent stem cell-conditioned medium on in vitro hypertrophic scarring fibroblast activation.

Hypertrophic scarring (HS) is a type of fibrosis that occurs in the skin, and is characterized by fibroblast activation and excessive collagen production. However, at present, therapeutic strategies for this condition are ineffective. Previous studies have identified that the mutual regulation of chronic inflammation, mechanical force and fibroblast activation leads to the formation of HS. Induced pluripotent stem cells (iPSCs) are novel bioengineered embryonic­like stem cells, initially created from mouse adult fibroblasts. The current study demonstrated that iPSC­conditioned medium (iPSC­CM) may significantly suppress hypertrophic scar fibroblast activation. It was observed that in the presence of iPSC­CM, the level of collagen I was markedly reduced and α­smooth muscle actin, a marker for myofibroblasts (activated fibroblasts that mediate mechanical force­induced HS formation), exhibited a significantly lower level of expression in human dermal fibroblasts (HDFs) activated with transforming growth factor­ß1. Additionally, iPSC­CM attenuated the local inflammatory cell response by blocking the adhesion of human acute monocytic leukemia cell monocytes and fibroblasts in vitro. In addition, the contractile ability of HDFs may be reduced by iPSC­CM. These observations suggest that iPSC­CM may protect against processes leading to hypertrophic scarring by attenuating fibroblast activation, blocking inflammatory cell recruitment and adhesion and reducing the contractile ability of fibroblasts.

Lumican Accelerates Wound Healing by Enhancing α2ß1 Integrin-Mediated Fibroblast Contractility.

Lumican is a dermatan sulfate proteoglycan highly expressed in connective tissue and has the ability to regulate collagen fibril assembly. Previous studies have shown that lumican is involved in wound healing, but the precise effects of lumican on reepithelialization and wound contraction, the two pivotal aspects of skin wound healing, have not been investigated. Here we explored the roles of lumican in fibroblast contractility, a main aspect of skin wound healing, by adopting mice skin wound healing model and the corresponding in vitro cellular experiments. Our results showed that lumican can promote skin wound healing by facilitating wound fibroblast activation and contraction but not by promoting keratinocyte proliferation and migration. Silencing of integrin α2 completely abolished the pro-contractility of lumican, indicating lumican enhances fibroblast contractility via integrin α2. Our study for the first time demonstrated that lumican can affect fibroblast's mechanical property, which is pivotal for many important pathological processes, such as wound healing, fibrosis, and tumor development, suggesting that lumican might have a potential to be used to modulate these processes.

Combined fascial flap and expanded skin flap for enveloping Medpor framework in microtia reconstruction.

The Medpor implant is another choice for a new auricular framework besides autogenous costal cartilage. However, its relatively frequent exposure and less-matching skin coverage discourage surgeons from using it. In this article, we present a new two-flap method, a combination of the temporoparietal fascial flap and the expanded skin flap, for wrapping the Medpor implant in microtia reconstruction. A staged surgical procedure was performed, including soft tissue expansion in the mastoid region, soft tissue expander removal, expanded skin flap and temporoparietal fascial flap formation, Medpor framework implantation, and the combined two-flap envelopment. Conventional lobule transposition and tragus reconstruction were accomplished for selected patients. In this study, a total of 22 microtias were reconstructed consecutively using this method. Eighteen patients were followed since the first surgery. The postoperative follow-up time ranged from 3 to 12 months. The draped soft tissue covering was thin enough to show the reconstructed ear with excellent, subtle contour when edema gradually vanished 3-6 months postoperatively. The new ear had a stable shape, and its skin color and texture matched the normal surrounding skin very well. No exposure or extrusion of the framework was observed in the series. The Medpor implant enveloped by both a temporoparietal fascial flap and an expanded cutaneous flap appears to be a promising alternative for the auricular framework in microtia reconstruction. Because of the wrapping tissues, auricular construction using a Medpor implant can be a safe, steady, and easily acceptable choice for both microtia patients and their physicians.

Etiology and management of axillary bromidrosis: a brief review.

BACKGROUND: Axillary bromidrosis is a distressing condition that poses significant social embarrassment in almost all the countries over the world. However, its definite etiology has not been generalized yet. There have been a lot of treatments for bromidrosis, which can be roughly divided into two types: conservative management and radical surgical therapy. In order to summarize the possible causes of axillary bromidrosis, a brief review of the literatures regarding bromidrosis was performed. METHODS: An English literature search from 1975 to June 2007 was completed with references to treatments for bromidrosis. A total of 29 papers about the treatment were selected to review. After a close reading, all the extracted information was imported into Microsoft Excel. RESULTS: Many therapies were carried out to treat bromidrosis, including nonoperative and operative ones. Almost all the authors thought that the nonoperative management, such as topical antiperspirants, systemic agents, and iontophoresis, did not have a permanent effect. Most surgeons (90%) chose surgical methods to remove axillary sweat glands for bromidrosis and 90.69% of the axillae had good results. CONCLUSION: Axillary sweat glands may play the most important role in the etiology of bromidrosis. In addition, axillary microorganism, hormone, and inherent also contribute to bromidrosis.

Aesthetic rhinoplasty of the Asian nasal tip: a brief review.

Tip surgery, the most important part of the rhinoplasty procedure, has entered a new era in the past few decades. Various treatment protocols have been attempted. To date, however, opinions on the management of the Asian tip have not been solidified. To generalize and provide appropriate guidelines for the treatment of typical Asian tips, an English literature search from 1977 to March 2007 was conducted. Finally, a total of 26 papers were selected for review. The full text of each paper was read carefully, and data were extracted. Then all extracted information was imported into Microsoft Excel. Nine articles treating 11 groups of patients described the suitable techniques for Asian nasal tips, with 81.8% of the groups advocating that the protocol include a grafting technique, 64% reporting use of the grafting technique alone, and 9% applying cartilage reduction and a suturing technique. Of the 11 (18%) groups, 2 attempted more than one technique. Because of the Asian nasal tip's innate qualities, success with nasal tip plasty for Asians depends on the combined application of appropriate suturing, grafting, and defatting, with grafting techniques contributing the most.

Increased expression of CD86 and reduced production of IL-12 and IL-10 by monocyte-derived dendritic cells from allergic asthmatics and their effects on Th1- and Th2-type cytokine balance.

BACKGROUND: In allergic asthma, allergen-specific T cells have a Th2-biased phenotype, and it is thought that dendritic cells (DCs) contribute to the induction of allergic immune responses. Therefore, we hypothesized that DCs from allergic asthmatics and healthy donors differ with regard to their preference to induce Th1 or Th2 immune responses. OBJECTIVES: To investigate differences in DC-expressed costimulatory molecules and DC-secreted cytokines between allergic asthmatics and healthy donors, and their influence on the Th1- and Th2-type cytokine balance. METHODS: Circulating monocytes from patients with allergic asthma and healthy donors were cultured with GM-CSF and IL-4, respectively, for 5 days and subsequently with lipopolysaccharide for 2 days to create mature DCs (mDCs). CD1a, CD83, CD40 and CD86 expression on mDCs was examined using a fluorescence-activated cell sorter. IL-12 and IL-10 secreted by mDCs were measured by ELISA. Naïve cord blood T cells were primed by mDCs from two groups, and IL-4 and IFN-gamma production by polarized T-helper cells (Th) was measured by ELISA. RESULTS: (1) CD86 expression on mDCs from allergic asthmatics was higher than that from healthy donors. (2) IL-12, IL-12p40 and IL-10 production by mDCs from allergic asthmatics was significantly lower than that from healthy donors, respectively. (3) IL-4 production by Th cells primed by mDCs from allergic asthmatics was increased compared with that from healthy donors. CONCLUSIONS: mDCs from allergic asthmatics preferentially priming naïve T cells towards Th2-cell development might be due to increased expression of CD86 and reduced production of IL-12 and IL-10.

[A study of phenotype and function of dendritic cells and secretory cytokine in allergic asthmatic patients].

OBJECTIVE: To investigate the deficiency of the expression of the phenotypes (CD(1a), CD(83), CD(40), CD(86)) and cytokines (IL-12 and IL-10) by human peripheral blood monocyte (PBMC)-derived dendritic cell (DCs) from asthmatic subjects, and their influence on naive T cell polarization. METHODS: Adherent cells were isolated from peripheral blood samples in asthmatic patients and in healthy volunteers, and were cultured with granulocyte-macrophage colony-stimulating factor and IL-4 as immature DC (iDC). iDCs were stimulated with lipopolysaccharide as mature DC (mDCs). Nonadherent cells were obtained from umbilical cord blood by idem methods, and naïve T cells were sorted by adding anti-CD(4) and anti-CD(45RA) in nonadherent cells respectively and magnetic microbeads. Naïve T cells and mDCs from two groups were co-cultured in complete RPMI1640 media respectively, and naive T cells polarized as T helper cells 1 (Th1) and Th2. The expression of the CD(1a), CD(83), CD(40) and CD(86) on mature DCs were examined by fluorescent activated cell sorter. IL-12 and IL-10 released by mDCs and IL-4 and IFNgamma produced by Th cells were measured by ELISA. RESULTS: (1) The expression of CD(86) on dendritic cells from atopic asthmatics was higher than that from healthy control subjects (40.75 +/- 3.99 vs 29.88 +/- 1.25, P < 0.01). (2) The levels of IL-12, IL-12p40 and IL-10 produced by DCs from asthmatic subjects were all significantly lower than those from healthy control group (217.79 +/- 118.65 vs 905.66 +/- 495.32, P < 0.01; 2072.22 +/- 1496.37 vs 5569.43 +/- 2922.75, P < 0.01; 336.89 +/- 261.52 vs 1425.00 +/- 1148.87, P < 0.05, respectively). (3) IL-4 production by Th2 cells which were primed by DCs from asthmatics was significantly increased as compared to that from control group (368.56 +/- 190.72 vs 584.91 +/- 290.13, P < 0.01); On the contrary, IFNgamma in the patient group was reduced as compared to that in the control group (425.33 +/- 164.94 vs 49.86 +/- 18.14, P < 0.05). (4) In the patient group, the level of IL-12 was positively correlated to that of IFNgamma (P < 0.05), negatively correlated to that of IL-4 (P < 0.05); IL-10 was negatively correlated to IL-4 (P < 0.05). (5) There was a positive correlation between IL-12 and IL-10 in the two groups (P < 0.01). CONCLUSION: Because of DC deficiency, naïve T cells preferentially polarize to Th2 which synthesize more Th2-type cytokine (i.e. IL-4) and T cell tolerance cannot be induced, which may be one of the important pathogenic mechanisms for allergic asthma.