Xenogeneic Bio-Root Prompts the Constructive Process Characterized by Macrophage Phenotype Polarization in Rodents and Nonhuman Primates
Xenogeneic Bio-Root Prompts the Constructive Process Characterized by Macrophage Phenotype Polarization in Rodents and Nonhuman Primates
复制标题
异种生物根促进啮齿动物和非人类灵长类动物巨噬细胞表型极化的构建过程
DOI：
10.1002/adhm.201601112
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发表时间：
2017-03-08
影响因子：
10
通讯作者：
Tian, Weidong
中科院分区：
文献类型：
--
作者：
Li, Hui;Sun, Jingjing;Tian, Weidong
使用异种基质再生组织或器官是解决同种移植供体基质短缺的一种很有前途的方法。这种方法的成功已被证明与巨噬细胞介导的纤维化动态平衡和组织重塑相关。以往的研究表明，处理后的牙本质基质(TDM)可以作为一种适合于同种异体牙根再生的生物活性基质。本研究通过猪TDM(PTDM)和同种异体牙囊细胞(DFC)的组合构建了异种生物工程牙根(Bio-Root)。巨噬细胞表型用于评估异种生物根在体外和体内的重塑过程。PTDM可促进人源性DFCs向成牙本质细胞分化。大鼠皮下组织中的异种生物根在移植后早期通过M1巨噬细胞的渗透促进建设性反应，并在后期增加恢复性M2表型。恒河猴颌骨生物根植入6个月后，可见牙周韧带样纤维伴巨噬细胞极化，呈Col-1、Periostin、βIII-微管蛋白阳性，呈成纤维细胞和血管等结构。重建的生物牙根具有消散咀嚼动力的生物力学特性。这些结果支持异种生物根在重建过程中能够维持纤维内环境的稳定，突出了异种基质在再生医学中的潜在应用。
Tissue or organ regeneration using xenogeneic matrices is a promising approach to address the shortage of donor matrices for allotransplantation. Success of such approach has been demonstrated to correlate with macrophage-mediated fibrotic homeostasis and tissue remodeling. The previous studies have demonstrated that treated dentin matrix (TDM) could be a suitable bioactive substrate for allogeneic tooth root regeneration. This study constructed xenogeneic bioengineered tooth root (bio-root) via a combination of porcine TDM (pTDM) with allogeneic dental follicle cells (DFCs). Macrophage phenotypes are used to evaluate the remodeling process of xenogeneic bio-roots in vitro and in vivo. pTDM can facilitate odontoblast differentiation of human derived DFCs. Xenogeneic bio-roots in rat subcutaneous tissue prompt constructive response via M1 macrophage infiltration during early postimplantation stages and increase restorative M2 phenotype at later stages. After implantation of bio-roots into jaws of rhesus monkeys for six months, periodontal ligament-like fibers accompanied by macrophage polarization are observed, which are positive for COL-1, Periostin, beta III-tubulin and display such structures as fibroblasts and blood vessels. The reconstructed bio-root possesses biomechanical properties for the dissipation of masticatory forces. These results support that xenogeneic bio-root could maintain fibrotic homeostasis during remodeling process and highlight the potential application of xenogeneic matrices in regenerative medicine.