Peripheral Blood Fibrocytes Enhancement of Wound Healing by Cell Proliferation, Re-Epithelialization, Contraction, and Angiogenesis

Peripheral Blood Fibrocytes Enhancement of Wound Healing by Cell Proliferation, Re-Epithelialization, Contraction, and Angiogenesis
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DOI:
10.1097/sla.0b013e3182251559
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发表时间:
2011-12-01
期刊:
影响因子:
9
通讯作者:
Guo, Lifei
Guo, Lifei
中科院分区:
医学1区
文献类型:
--
作者:
Kao, Huang-Kai;Chen, Bin;Guo, Lifei

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目的:目的:研究纤维细胞的体外特性和功能特性,并探讨纤维细胞注射促进糖尿病小鼠皮肤愈合的体内作用机制。背景:纤维细胞是造血干细胞,可能作为成纤维细胞或肌成纤维细胞样细胞的前体,在组织修复中发挥作用。在体外,外周血(PB)纤维细胞的时间依赖性表型表达用抗CD 11b、抗CD 45、抗Col-I和抗α-SMA抗体染色。用逆转录聚合酶链反应检测成纤维细胞和真皮成纤维细胞的功能特性。在体内,糖尿病小鼠的全层伤口通过尾静脉注射用纤维细胞、真皮成纤维细胞或磷酸盐缓冲盐水(PBS)处理。研究了伤口愈合动力学,包括伤口收缩、再上皮化和微观指标,如细胞增殖、血管生成和肉芽生长。促炎因子,促纤维化因子,生长因子和细胞外基质成分的表达进行了测量在伤口tissue.Results:纤维细胞逐渐失去其造血细胞标志物,并在体外分化过程中增加间充质细胞标志物。与真皮成纤维细胞和PBS处理的伤口相比,纤维细胞通过真皮细胞增殖、角质形成细胞增殖伴再上皮化和血管生成来刺激伤口愈合。血管生成标志物(VEGF和b-FGF),生长因子(TGF-β,PDGF-A和FGF-7),趋化因子(MCP-1和MIP-1 α),和细胞外基质(胶原-I和α-SMA)的表达上调在fibrocyte-treated wounds.Conclusion:外周血纤维细胞可以通过刺激细胞增殖,再上皮化,和血管生成在糖尿病小鼠实验模型中加速伤口愈合。纤维细胞的应用可能代表了所有手术领域治疗慢性伤口的潜在临床解决方案。
Objective: To identify the in vitro characteristics and functional properties of fibrocytes and investigate the in vivo mechanism of action of fibrocytes injection in accelerating the cutaneous healing process in diabetic mice.Background: Fibrocytes are hematopoietic derived stem cells that may have a role in tissue repair, perhaps as the precursors of fibroblast-or myofibroblast-like cells.Methods: In vitro, the time-dependent phenotypic expression of peripheral blood (PB) fibrocytes was stained with anti-CD11b, anti-CD45, anti-Col-I, and anti-alpha-SMA antibodies. The functional properties of fibrocytes and dermal fibroblasts were tested by using reverse-transcriptase polymerase chain reaction. In vivo, full thickness wounds in diabetic mice were treated either with fibrocytes, dermal fibroblasts, or phosphate buffered saline (PBS) through tail vein injection. Wound healing kinetics, including wound contraction, re-epithelialization, and microscopic metrics such as cell proliferation, angiogenesis, and granulation growth were investigated. Expression of proinflammatory factors, profibrotic factors, growth factors, and extracellular matrix components were measured in wound tissues.Results: Fibrocytes gradually lose their hematopoietic cell markers and increase mesenchymal cell markers during differentiation in vitro. Fibrocytes stimulate wound healing by dermal cell proliferation, keratinocyte proliferation with re-epithelialization, and angiogenesis compared with dermal fibroblast and PBS treated wounds. Expression of angiogenesis markers (VEGF and b-FGF), growth factors (TGF-beta, PDGF-A, and FGF-7), chemokines (MCP-1 and MIP-1 alpha), and extracellular matrix (collagen-I and alpha-SMA) were upregulated in fibrocyte-treated wounds.Conclusion: Peripheral blood fibrocytes can accelerate wound healing by stimulating cell proliferation, re-epithelialization, and angiogenesis in a diabetic mice experimental model. The application of fibrocytes may represent a potential clinical solution for the treatment of chronic wounds across all fields of surgery.