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1.
Bone marrow-derived cells contribute to epithelial engraftment during wound healing 总被引:9,自引:0,他引:9
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Borue X Lee S Grove J Herzog EL Harris R Diflo T Glusac E Hyman K Theise ND Krause DS 《The American journal of pathology》2004,165(5):1767-1772
Recent findings suggest that bone marrow-derived cells (BMDC) may contribute to tissue maintenance throughout the body. However, it is not yet known whether marrow-derived epithelial cells are capable of undergoing proliferation. Our laboratory has shown that BMDC engraft as keratinocytes in the skin at low levels (= 1%) in the absence of injury. Here we show that skin damage affects the degree of engraftment of BMDC as keratinocytes and that the keratinocytes are actively cycling. Female mice reconstituted with sex-mismatched BM were wounded by punch biopsy and incision. At the wound site, engraftment of BMDC as epidermal cells increased within 1 day, and continued to increase to approximately 4% by 3 weeks after injury. Using a Cre-lox system, fusion of BMDC with epithelial cells was ruled out. BMDC-derived epithelial cells at the wound edges expressed Ki67, a marker for actively cycling cells, and this proliferation correlated with an increase in the number of donor-derived cells within the wound. Donor-derived cytokeratin 5-expressing cells were rare, suggesting that BMDC do not engraft as epidermal stem cells, and the level of engraftment peaked and then decreased over time, further suggesting that BMDC may assist in early wound healing by engrafting as transit-amplifying cells, which then differentiate into keratinocytes. 相似文献
2.
IL-33 is a newly discovered member of the IL-1 family and has been identified as a potent inducer of Th2 type immunity. Emerging evidence imply that IL-33 may also act as an alarm to alert the immune system when released by epithelial barrier tissues during trauma or infection. In this study, we further investigate the potential efficacy of IL-33 on dermal wound healing in streptozotocin–induced diabetic mice. A full-thickness skin wound was generated on the back of diabetic mice and treated with IL-33 or vehicle topically. Our data showed that IL-33 delivery contributed to diabetic wound closure with wounds gaping narrower and exhibiting elevated re-epithelialization. IL-33 promoted the new extracellular matrix (ECM) deposition and angiogenesis formation, which indicates an important role of IL-33 on matrix synthesis and neovascularization. Meanwhile, IL-33 accelerated the development of M2 macrophages in wound sites in vivo, and amplified IL-13-induced polarization of bone marrow-derived macrophages toward a M2 phenotype in vitro. Furthermore, IL-33-amplified M2 macrophages augmented the proliferation of fibroblasts and ECM deposition. All together, these results strongly suggest manipulation of IL-33-mediated signal might be a potential therapeutic approach for diabetic skin wounds. 相似文献
3.
Olerud JE 《Journal of biomaterials science. Polymer edition》2008,19(8):1007-1020
Delayed healing of chronic ulcers in patients with diabetes and infections resulting from percutaneous medical devices (e.g., vascular access catheters) not only plays a major role in morbidity and mortality, but is a major burden to our healthcare system. In this paper, we review models to study diabetic wound healing and the wound-healing response associated with implanted percutaneous implants. 相似文献
4.
Shuichi Yoneda Shichiro Abe Isao Taguchi Nobuhide Masawa Katsumi Inoue Teruo Inoue 《Cardiovascular pathology》2012,21(6):511-514
An 86-year-old man died suddenly 5 months after implantation of a zotarolimus-eluting stent. Two zotarolimus-eluting stents were placed to treat a highly calcified diffuse lesion in the proximal-to-mid right coronary artery. The lesion was fully covered by the two stents, and intravascular ultrasound showed complete stent apposition. However, an X-ray at autopsy showed that the proximal stent was fractured. Although we thought that thrombotic occlusion at the fracture site might have caused his sudden death, no thrombus was present. In addition, in the other sites where the stents were optimally dilated, there was stent malapposition and peri-strut inflammation including macrophage infiltration, giant cells, polymer phagocytosis, and neovascularization in the neointima. Even with a second-generation drug-eluting stent, such as the zotarolimus-eluting stent, wound healing may be impaired at the stent-injured vessel site. 相似文献
5.
M. S. Bitar 《The American journal of pathology》1998,152(2):547-554
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Inflammation Research - The failure in timely healing of wounds is a central feature in chronic wounds that leads to physiological, psychological and economic burdens. Macrophages have been... 相似文献
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微小核糖核酸(microRNA/miRNA)作为一类进化上保守的非编码小分子RNA,参与基因转录后的表达与
调控,其表达模式有一定的时间性和空间性,体现在不同的miRNAs在不同组织、不同发育阶段的表达水平差异。
某些miRNAs能够促进创面愈合,在创面愈合的炎症期抑制炎性介质的表达;某些miRNAs能够促进增生期创面
细胞的增殖、迁移,有利于创面的快速修复;在创面重塑期,某些miRNAs又能够通过抑制无痕愈合信号通路的
相关蛋白质来促使瘢痕修复。糖尿病创面通常伴随糖尿病周围神经病变、糖尿病血管病变和感染。部分miRNAs
通过调控特定基因的表达水平,激活或抑制不同且特定的信号通路,一定程度上促进了糖尿病创面的愈合。本文
主要综述了miRNA在创面愈合过程不同阶段的调控研究进展,以及miRNAs促进、抑制糖尿病创面愈合的机制,
以期为后续研究开拓新的思路。 相似文献
11.
Nicotine accelerates angiogenesis and wound healing in genetically diabetic mice 总被引:19,自引:0,他引:19
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Jacobi J Jang JJ Sundram U Dayoub H Fajardo LF Cooke JP 《The American journal of pathology》2002,161(1):97-104
Recently, we have discovered an endogenous cholinergic pathway for angiogenesis mediated by endothelial nicotinic acetylcholine receptors (nAChRs). Since angiogenesis plays a major role in wound repair, we hypothesized that activation of nAChRs with nicotine would accelerate wound healing in a murine excisional wound model. In genetically diabetic and control mice full-thickness skin wounds (0.8 cm) were created on the dorsum and topically treated over 7 days with either vehicle (phosphate-buffered saline, PBS) or nicotine (10(-8) mol/L, 10(-9) mol/L; each, n = 5). Wound size was measured over 14 days followed by resection, histological analysis, and quantitation of vascularity. In diabetic animals an agonist (epibatidine, 10(-10) mol/L) or antagonist (hexamethonium, 10(-4) mol/L) of nAChRs as well as the positive control basic fibroblast growth factor (bFGF, 25 microg/kg) were also tested. To further study the role of endothelial nAChRs in angiogenesis, we used an ex vivo vascular explant model. In diabetic mice wound healing was markedly impaired. Nicotine significantly accelerated wound healing as assessed by closure rate and histological score. The effects of nicotine were equal to bFGF and were mimicked by epibatidine and blocked by hexamethonium. Histomorphometry revealed increased neovascularization in animals treated with nicotine. Furthermore, capillary-like sprouting from vascular explants was significantly enhanced by nicotine. In conclusion, agonist-induced stimulation of nAChRs accelerates wound healing in diabetic mice by promoting angiogenesis. We have discovered a cholinergic pathway for angiogenesis that is involved in wound healing, and which is a potential target for therapeutic angiogenesis. 相似文献
12.
Diabetic foot disease is a major health problem, which affects 15% of the 200 million patients with diabetes worldwide. Diminished peripheral blood flow and decreased local neovascularization are critical factors that contribute to the delayed or nonhealing wounds in these patients. The correction of impaired local angiogenesis may be a key component in developing therapeutic protocols for treating chronic wounds of the lower extremity and diabetic foot ulcers. Endothelial progenitor cells (EPCs) are the key cellular effectors of postnatal neovascularization and play a central role in wound healing, but their circulating and wound-level numbers are decreased in diabetes, implicating an abnormality in EPC mobilization and homing mechanisms. The deficiency in EPC mobilization is presumably due to impairment of eNOS-NO cascade in bone marrow (BM). Hyperoxia, induced by a clinically relevant hyperbaric oxygen therapy (HBO) protocol, can significantly enhance the mobilization of EPCs from the BM into peripheral blood. However, increased circulating EPCs failed to reach to wound tissues. This is partly a result of downregulated production of SDF-1alpha in local wound lesions with diabetes. Administration of exogenous SDF-1alpha into wounds reversed the EPC homing impairment and, with hyperoxia, synergistically enhanced EPC mobilization, homing, neovascularization, and wound healing. 相似文献
13.
Dermal accumulation of advanced glycation end products (AGEs) has increasingly been implicated as the underlying cause of delayed diabetic wound healing. Devising an in vitro model to adequately mimic glycated tissues will facilitate investigation into the mechanism of glycation in conjunction with exploration of new approaches or improvement of current therapies for treating diabetic chronic wounds. Collagen matrices were artificially glycated and the presence of AGEs was demonstrated by immunostaining. Both the mechanical properties of the collagen matrices and their interactions with fibroblasts (morphology, attachment, proliferation, and migration) were altered after glycation, moreover, there was evidence of impairment on extracellular matrix (ECM) remodeling as well as inhibition of cell-induced material contraction. The actin cytoskeletons of the fibroblasts residing in the glycated collagen matrices were reorganized. In vivo mice full-thickness dermal wound models implanted with glycated collagen matrices showed delayed wound healing response. Thus, the glycated collagen matrix is an adequate in vitro model to mimic glycated tissues and could serve as a facile experimental tool to investigate the mechanism of glycation in conjunction with exploration of new approaches or improvement of current therapies for treating diabetic wounds. 相似文献
14.
Storr SJ Safuan S Mitra A Elliott F Walker C Vasko MJ Ho B Cook M Mohammed RA Patel PM Ellis IO Newton-Bishop JA Martin SG 《Modern pathology》2012,25(4):493-504
The aims of this study were to investigate the role of vascular invasion (blood and lymphatic), vessel density and the presence of tumour-associated macrophages as prognostic markers in 202 cutaneous melanoma patients. Sections of primary melanoma were stained with lymphatic-specific antibody D2-40 to assess lymphatic vessel invasion and density in intratumoural and peritumoural areas; an antibody against endothelial marker CD34 was used to determine blood vessel invasion and density, and an antibody against CD68 was used to determine macrophage counts. Immunohistochemically determined vascular invasion (combined blood and lymphatic) was compared with that determined using haematoxylin and eosin (H&E) staining. The use of immunohistochemistry increased detection of vascular invasion from 8-30% of patients, and histological exam of H&E-stained tissue was associated with a false positive rate of 64%. Lymphatic vessel invasion occurred at a much higher frequency than blood vessel invasion (27 and 4% of patients, respectively). Although immunohistochemically detected vessel invasion was significantly associated with histological markers of adverse prognosis, such as increased Breslow thickness, ulceration and mitotic rate (all P<0.001), no associations with relapse-free or overall survival were observed. High macrophage counts were significantly associated with markers of aggressive disease, such as Breslow thickness, ulceration and mitotic rate (P<0.001, P<0.001, P=0.005, respectively), and lymphatic vessel invasion and high microvessel density (P=0.002 and P=0.003, respectively). These results suggest that vascular invasion is more accurately detected using immunohistochemistry and occurs predominantly via lymphatic vessels. The association of vessel characteristics with histological characteristics of the primary melanoma provides evidence for their biological importance in melanoma, but that they were not associated with clinical outcome attests to the value of existing histological prognostic biomarkers. We note that a high macrophage count may be associated with neovascularisation and primary tumour growth, and may also promote invasion through lymphatic vessels. 相似文献
15.
Effects of epicatechin gallate on wound healing and scar formation in a full thickness incisional wound healing model in rats
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Catechins are naturally occurring polyphenolic compounds with putative anti-inflammatory, antioxidant and free radical scavenging effects in vitro. However, their potential effects in vivo have not been established. Therefore we have investigated the effects of the catechin epicatechin gallate (ECG), on scar formation in a full thickness incisional model of wound healing in rats. ECG showed a significant improvement in the quality of scar formation both in terms of maturity and orientation of the collagen fibers. An increase in inducible nitric oxide synthase and cyclooxygenase-2 and a decrease in arginase-I activity and protein levels were observed at earlier time points. In addition, an increase in the number of new blood vessels was observed in the ECG-treated group. This correlated with the protein levels of vascular endothelial growth factor, the most potent angiogenic protein known. This study has therefore demonstrated, for the first time, that catechins, namely ECG, can significantly improve the quality of wound healing and scar formation. These effects may in part be due to an acceleration of the angiogenic response and an up-regulation of the enzymes nitric oxide synthase and cyclooxygenase. 相似文献
16.
Rita E Mirza Milie M Fang Margaret L Novak Norifumi Urao Audrey Sui William J Ennis Timothy J Koh 《The Journal of pathology》2015,236(4):433-444
Macrophages undergo a transition from pro‐inflammatory to healing‐associated phenotypes that is critical for efficient wound healing. However, the regulation of this transition during normal and impaired healing remains to be elucidated. In our studies, the switch in macrophage phenotypes during skin wound healing was associated with up‐regulation of the peroxisome proliferator‐activated receptor (PPAR)γ and its downstream targets, along with increased mitochondrial content. In the setting of diabetes, up‐regulation of PPARγ activity was impaired by sustained expression of IL‐1β in both mouse and human wounds. In addition, experiments with myeloid‐specific PPARγ knockout mice indicated that loss of PPARγ in macrophages is sufficient to prolong wound inflammation and delay healing. Furthermore, PPARγ agonists promoted a healing‐associated macrophage phenotype both in vitro and in vivo, even in the diabetic wound environment. Importantly, topical administration of PPARγ agonists improved healing in diabetic mice, suggesting an appealing strategy for down‐regulating inflammation and improving the healing of chronic wounds. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. 相似文献
17.
PDGF and FGF stimulate wound healing in the genetically diabetic mouse. 总被引:22,自引:11,他引:22
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D. G. Greenhalgh K. H. Sprugel M. J. Murray R. Ross 《The American journal of pathology》1990,136(6):1235-1246
To examine the effects of recombinant growth factors in vivo, impaired wound healing was studied in genetically diabetic C57BL/KsJ-db/db mice. Large full-thickness skin wounds made on the backs of these mice exhibited significant delays in the entry of inflammatory cells into the wound, the formation of granulation tissue, and in wound closure when compared to their nondiabetic littermates. Recombinant human platelet-derived growth factor (rPDGF-BB, 1 or 10 micrograms), recombinant human basic fibroblast growth factor (rbFGF, 1 micrograms), or combinations of both were applied topically to the wounds for 5 to 14 days after wounding. Diabetic mouse wounds treated with rPDGF-BB or rbFGF had many more fibroblasts and capillaries in the wound bed at 10 and 21 days than did wounds treated with the vehicle alone. The animals treated with growth factors also had significantly greater wound closure at 21 days than those treated with the vehicle. Combinations of rPDGF-BB and rbFGF improved all parameters of healing but not to a greater extent than either growth factor alone. The effectiveness of rPDGF-BB and rbFGF suggest that recombinant growth factors may be useful in the treatment of patients with deficient wound repair. 相似文献
18.
Murine macrophage chemokine receptor CCR2 plays a crucial role in macrophage recruitment and regulated inflammation in wound healing
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Anna E. Boniakowski Andrew S. Kimball Amrita Joshi Matt Schaller Frank M. Davis Aaron denDekker Andrea T Obi Bethany B. Moore Steve L. Kunkel Katherine A. Gallagher 《European journal of immunology》2018,48(9):1445-1455
Macrophages play a critical role in the establishment of a regulated inflammatory response following tissue injury. Following injury, CCR2+ monocytes are recruited from peripheral blood to wound tissue, and direct the initiation and resolution of inflammation that is essential for tissue repair. In pathologic states where chronic inflammation prevents healing, macrophages fail to transition to a reparative phenotype. Using a murine model of cutaneous wound healing, we found that CCR2‐deficient mice (CCR2?/?) demonstrate significantly impaired wound healing at all time points postinjury. Flow cytometry analysis of wounds from CCR2?/? and WT mice revealed a significant decrease in inflammatory, Ly6CHi recruited monocyte/macrophages in CCR2?/? wounds. We further show that wound macrophage inflammatory cytokine production is decreased in CCR2?/? wounds. Adoptive transfer of mT/mG monocyte/macrophages into CCR2+/+ and CCR2?/? mice demonstrated that labeled cells on days 2 and 4 traveled to wounds in both CCR2+/+ and CCR2?/? mice. Further, adoptive transfer of monocyte/macrophages from WT mice restored normal healing, likely through a restored inflammatory response in the CCR2‐deficient mice. Taken together, these data suggest that CCR2 plays a critical role in the recruitment and inflammatory response following injury, and that wound repair may be therapeutically manipulated through modulation of CCR2. 相似文献
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目的探讨糖尿病足截肢平面和截肢后切口愈合的影响因素。方法收集1998年1月至2009年12月出院的82例糖尿病足截肢患者临床资料,分别分析糖尿病足截肢平面与病程、外周神经障碍、血管狭窄程度、Wagner分级、创面感染情况的相关性,以及截肢后切口愈合情况与年龄、围手术期血糖控制水平、血管狭窄程度、外周神经障碍、Wagner分级、创面感染情况的相关性。结果糖尿病足截肢平面的选择与病程、外周神经障碍、血管狭窄程度有关(P0.05);截肢后切口愈合情况与年龄、血糖控制水平及血管狭窄程度相关(P0.05)。结论糖尿病足截肢平面的选择应通过病程、外周神经病变和血管狭窄程度量化分析;高龄、围手术期血糖控制不佳及重度血管狭窄是糖尿病足截肢后切口愈合欠佳的主要因素。 相似文献
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糖尿病慢性皮肤伤口的愈合,是临床治疗中的难点和基础研究中的热点。传统治疗方法效果并不理想,而组织工程技术的发展,为其治疗提供了新途径。现今已有将壳寡糖作为伤口敷料的研究,并引起越来越多的关注,但关于壳寡糖用于糖尿病难愈性创面的研究并不多。本篇综述将概述壳寡糖促进伤口愈合的生物学机制及特点,以及糖尿病皮肤创面的病理学改变,总结壳寡糖在糖尿病皮肤伤口愈合中的研究进展。 相似文献