SDF-1趋化循环成纤维细胞治疗皮肤慢性溃疡的研究

Difficulty in tissue regeneration caused by decreased functional cells and abnormality of stem cell homing are the key reasons of delayed or nonhealing wound. Studies have indicated the significant effects of wound healing by stem cell therapy and dicreased expression of SDF-1 in chronic skin ulers such as diabetic foot ulcer. CFs is the effector cell which was mobilized in the early stage of wound and participated in the healing process. CXCR4 is expressed in these cells and stem mobilization is trigger by SDF-1/CXCR4 axis. There are no reports considering the treatments of chronic skin ulcer by CFs which was mobilized by SDF-1. So we suggest that increased expression of SDF-1 in the local area could trigger the mobilization of CFs and enhance the wound healing process. We use GFP tracer technique, cell co-culture system, stem cell transplantation, cell biology and molecular biology technique to study the mechanism of stem cell homing from the relation of SDF-1 and CFs mobiliztion, and analyze the effects of wound healing in those chronic skin ulcers in different levels of neovasculariztion, epithelialization and dermal regeneration. Study could provide the evidences in the treatment of chronic skin ulcer by stem cell mobilization, and establish the base for clinical application.

功能性细胞减少和干细胞趋化障碍引发组织再生困难是创伤慢性化的重要原因。研究证明干细胞治疗慢性创伤有显著效果，糖尿病溃疡等皮肤慢性溃疡组织内干细胞趋化因子SDF-1存在低表达现象。CFs是创伤早期被动员并参与修复的效应细胞，特异性表达CXCR4；SDF-1/CXCR4结合能够趋化干细胞在体内定向移动。应用SDF-1趋化CFs治疗皮肤慢性溃疡目前未见报道。我们假设：溃疡局部提高SDF-1浓度能够趋化CFs定植并分化为效应细胞促进创伤愈合过程。课题应用GFP细胞示踪、细胞共培养、干细胞移植、细胞生物学和分子生物学等技术，从SDF-1与CFs定植的关系探讨干细胞趋化机制；从血管发生、上皮化和真皮再生的细胞、分子和组织水平分析CFs促进皮肤慢性溃疡愈合的作用。研究为应用干细胞趋化作用治疗皮肤慢性溃疡提供实验依据，并为临床应用奠定基础。

功能性细胞减少和干细胞趋化障碍引发组织再生困难是创伤慢性化的重要原因。研究证明干细胞治疗慢性创伤有显著效果，糖尿病溃疡等皮肤慢性溃疡组织内干细胞趋化因子SDF-1存在低表达现象。CFs是创伤早期被动员并参与修复的效应细胞，特异性表达CXCR4；SDF-1/CXCR4结合能够趋化干细胞在体内定向移动。应用SDF-1趋化CFs治疗皮肤慢性溃疡目前未见报道。我们假设溃疡局部提高SDF-1浓度能够趋化CFs定植并分化为效应细胞促进创伤愈合过程。应用GFP细胞示踪、细胞共培养、干细胞移植、细胞生物学和分子生物学等技术，从SDF-1与CFs定植的关系探讨干细胞趋化机制，我们从血管发生、上皮化和真皮再生的细胞、分子和组织水平分析CFs促进皮肤慢性溃疡愈合的作用。结果发现炎症反应对SDF-1的表达具有重要影响，而且SDF-1在不同时间段表达的部位不同，通过增加皮肤创面局部SDF-1的浓度能够促进CFs向创伤部位移动，参与组织修复的过程。移植后对动物模型愈合创面研检测结果发现：CD31、VEGF、Collagen I/III、SMA、CK14/17/19以及CD14和CD34均在移植后的不同时间段内显著升高，证实了移植的CFs在创面愈合过程中的不同时间起到的不同修复作用和表面标志物的变化。研究为应用干细胞趋化作用治疗皮肤慢性溃疡提供实验依据，并为临床应用奠定基础。