Transplantation of Fetal Instead of Adult Fibroblasts Reduces the Probability of Ectopic Ossification During Tendon Repair
Transplantation of Fetal Instead of Adult Fibroblasts Reduces the Probability of Ectopic Ossification During Tendon Repair
复制标题
移植胎儿而不是成年成纤维细胞可降低肌腱修复过程中异位骨化的可能性
DOI：
10.1089/ten.tea.2013.0296
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发表时间：
2014-07-01
影响因子：
4.1
通讯作者：
Chen, Xiao
中科院分区：
文献类型：
--
作者：
Fang, Zhi;Zhu, Ting;Chen, Xiao
虽然细胞移植治疗可以有效地促进功能性肌腱修复，但肌腱再生过程中偶尔发生异位骨化会破坏其疗效。移植细胞类型对异位骨化的影响尚未得到系统评价。本研究比较了移植小鼠胎儿成纤维细胞（FF）和其成人对应物（成人成纤维细胞[AF]）后肌腱修复过程中异位骨化的发生率。采用碱性磷酸酶（ALP）染色、免疫荧光和基因表达分析等方法比较成纤维细胞和成纤维细胞体外自发成骨分化的情况。采用X线、组织学和基因表达分析等方法研究小鼠跟腱修复模型中异位骨化的发生。体外ALP染色和免疫荧光检测结果显示，成骨细胞自发性成骨分化能力较弱，Runx 2表达较低。对于体内研究，FF移植组在移植后14周显示出减少的异位骨化（2/7对7/7，Mann-Whitney检验p<0.01）和增强的肌腱修复（在第6周的一般组织学评分，7.53对10.56，p<0.05）。在AFs移植组中，在6周时形成更多的软骨细胞，并且所有小鼠在移植后14周时形成骨髓。再生组织的基因表达分析显示，在肌腱修复的早期阶段，AFs组中转化生长因子β 1（TGF-β1）和转化生长因子β 3（TGF-β3）的表达水平显著较高。我们的研究表明，移植胎儿而不是AF是更有希望的肌腱修复，强调种子细胞的来源肌腱修复的重要性。
Although cell transplantation therapy can effectively promote functional tendon repair, occasional ectopic ossification during tendon regeneration undermines its efficacy. The effect of transplanted cell types on ectopic ossification has not yet been systematically evaluated. This study compared the rate of ectopic ossification during tendon repair upon transplantation with mouse fetal fibroblasts (FFs) and their adult counterparts (adult fibroblasts [AFs]). Alkaline phosphatase (ALP) staining, immunofluorescence, and gene expression analysis were used to compare the spontaneous osteogenic differentiation of FFs and AFs in vitro. X-ray, histology, and gene expression analysis were used to investigate the ectopic ossification in a mouse Achilles tendon repair model in vivo. ALP staining and immunofluorescence data in vitro showed that FFs had less spontaneous osteogenic differentiation capacity, and lower expression of runt-related transcription factor 2 (runx2). For the in vivo study, the FFs transplant group displayed reduced ectopic ossification (2/7 vs. 7/7, Mann-Whitney test p<0.01) at 14 weeks post-transplantation and enhanced tendon repair (general histological score at week 6, 7.53 vs. 10.56, p<0.05). More chondrocytes formed at 6 weeks, and all mice developed bone marrow at 14 weeks post-transplantation in the AFs transplant group. Gene expression analysis of the regenerated tissue showed significantly higher expression levels of transforming growth factor beta1 (TGF-β1) and transforming growth factor beta3 (TGF-β3) in the AFs group during the early stages of tendon repair. Our study demonstrates that transplantation of fetal instead of AFs is more promising for tendon repair, underscoring the importance of the origin of seed cells for tendon repair.