Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Ann Surg. 2011 Dec;254(6):1066-74. doi: 10.1097/SLA.0b013e3182251559.
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.
Fibrocytes are hematopoietic derived stem cells that may have a role in tissue repair, perhaps as the precursors of fibroblast- or myofibroblast-like cells.
In vitro, the time-dependent phenotypic expression of peripheral blood (PB) fibrocytes was stained with anti-CD11b, anti-CD45, anti-Col-I, and anti-α-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.
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-β, PDGF-A, and FGF-7), chemokines (MCP-1 and MIP-1α), and extracellular matrix (collagen-I and α-SMA) were upregulated in fibrocyte-treated wounds.
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.
鉴定纤维细胞的体外特征和功能特性，并研究纤维细胞注射加速糖尿病小鼠皮肤愈合过程的体内作用机制。
纤维细胞是造血来源的干细胞，可能在组织修复中发挥作用，也许是成纤维细胞或肌成纤维细胞样细胞的前体。
在体外，通过抗 CD11b、抗 CD45、抗 Col-I 和抗 α-SMA 抗体对外周血（PB）纤维细胞的时间依赖性表型表达进行染色。通过逆转录聚合酶链反应测试纤维细胞和真皮成纤维细胞的功能特性。在体内，通过尾静脉注射将纤维细胞、真皮成纤维细胞或磷酸盐缓冲盐水（PBS）用于糖尿病小鼠的全层伤口。研究了伤口愈合动力学，包括伤口收缩、再上皮化以及细胞增殖、血管生成和肉芽生长等微观指标。测量了伤口组织中促炎因子、促纤维化因子、生长因子和细胞外基质成分的表达。
纤维细胞在体外分化过程中逐渐失去造血细胞标志物，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、角质形成细胞增殖和再上皮化以及血管生成来刺激伤口愈合。在纤维细胞处理的伤口中，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-1α）和细胞外基质（胶原-I 和 α-SMA）的表达上调。
外周血纤维细胞可通过刺激糖尿病小鼠实验模型中的细胞增殖、再上皮化和血管生成来加速伤口愈合。纤维细胞的应用可能代表了治疗所有外科领域慢性伤口的潜在临床解决方案。
