Stem Cells, Wound Repair & Regeneration Group, Cardiff Institute of Tissue Engineering and Repair, Oral and Biomedical Sciences, School of Dentistry, Cardiff University, Cardiff CF14 4XY, UK.
Division of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK.
Int J Mol Sci. 2018 Mar 27;19(4):1001. doi: 10.3390/ijms19041001.
: Chronic skin wounds are a growing financial burden for healthcare providers, causing discomfort/immobility to patients. Whilst animal chronic wound models have been developed to allow for mechanistic studies and to develop/test potential therapies, such systems are not good representations of the human chronic wound state. As an alternative, human chronic wound fibroblasts (CWFs) have permitted an insight into the dysfunctional cellular mechanisms that are associated with these wounds. However, such cells strains have a limited replicative lifespan and therefore a limited reproducibility/usefulness. : To develop/characterise immortalised cell lines of CWF and patient-matched normal fibroblasts (NFs). : Immortalisation with human telomerase resulted in both CWF and NF proliferating well beyond their replicative senescence end-point (respective cell strains senesced as normal). Gene expression analysis demonstrated that, whilst proliferation-associated genes were up-regulated in the cell lines (as would be expected), the immortalisation process did not significantly affect the disease-specific genotype. Immortalised CWF (as compared to NF) also retained a distinct impairment in their wound repopulation potential (in line with CWF cell strains). : These novel CWF cell lines are a credible animal alternative and could be a valuable research tool for understanding both the aetiology of chronic skin wounds and for therapeutic pre-screening.
慢性皮肤伤口给医疗保健提供者带来了日益增长的经济负担,给患者带来不适和行动不便。虽然已经开发出动物慢性伤口模型来允许进行机制研究和开发/测试潜在的治疗方法,但这些系统不能很好地代表人类慢性伤口状态。作为替代方案,人类慢性伤口成纤维细胞(CWF)允许深入了解与这些伤口相关的功能失调的细胞机制。然而,这些细胞系的复制寿命有限,因此其可重复性和有用性也有限。
开发/表征 CWF 和患者匹配的正常成纤维细胞(NF)的永生化细胞系。
人端粒酶的永生化导致 CWF 和 NF 的增殖远远超过其复制衰老终点(各自的细胞系按正常情况衰老)。基因表达分析表明,虽然细胞系中增殖相关基因上调(正如预期的那样),但永生化过程并没有显著影响特定于疾病的基因型。与 NF 相比,永生化的 CWF (与 CWF 细胞系一致)也保留了其在伤口再填充潜力方面的明显缺陷。
这些新型 CWF 细胞系是一种可靠的动物替代物,可作为了解慢性皮肤伤口病因和治疗性预筛选的有价值的研究工具。