Xenogeneic native decellularized matrix carrying PPARγ activator RSG regulating macrophage polarization to promote ligament-to-bone regeneration
Xenogeneic native decellularized matrix carrying PPARγ activator RSG regulating macrophage polarization to promote ligament-to-bone regeneration
复制标题
异种天然脱细胞基质携带 PPARγ 激活剂 RSG 调节巨噬细胞极化，促进韧带骨再生。
DOI：
10.1016/j.msec.2020.111224
复制
发表时间：
2020-11-01
影响因子：
7.9
通讯作者：
Guo, Weihua
中科院分区：
文献类型：
--
作者：
Han, Xue;Liao, Lijun;Guo, Weihua
宿主对组织工程组织或器官的免疫反应直接决定了移植物的存活和与宿主的融合。我们和其他先前的研究已经成功地基于同种异体天然脱细胞基质（aNDM）再生器官/组织。但是，非常有限的aNDM在临床上阻碍了人工器官/组织的应用，以解决高发生率的天然器官/组织损失。然而，异种NDM会引起宿主免疫排斥反应，导致移植失败。本研究构建了携带免疫调节剂罗格列酮（Rosiglitazone，xNDM-RSG）的异种（猪）NDM（xNDM），评价了xNDM的理化性质、免疫调节特性及其对组织再生的影响。结果表明，xNDM-RSG对牙源性干细胞的增殖和分化无影响。此外，xNDM-RSG还可以有效地降低IL-1和TNF α的表达，并增加IL-10和TGF β的表达，以实现有利的免疫调节，并通过PPAR γ诱导替代活化的巨噬细胞（M2巨噬细胞）拮抗经典活化的巨噬细胞（M1巨噬细胞）来促进韧带-骨再生。同时xNDM-RSG明显减少种植体的吸收，促进再生韧带-骨表达与天然牙和骨相关的关键蛋白（ALP、OPN、DSP）。本研究表明，蛋白吸附可加重免疫炎症反应，而xNDM-RSG可通过促进巨噬细胞极化，有效控制宿主免疫反应，加速组织修复和再生，为提高异种脱细胞生物材料人工器官或组织移植存活率提供了新的策略。
Host immune response to tissue engineering tissues or organs directly determines the graft survival and the integration with host. Our and other previous studies have successfully regenerated the organs/tissues based on allogeneic native decellularized matrix (aNDM). But the very limited aNDM clinically hinders the artificial organs/tissues application to resolve the native organs/tissues loss with high incidence. However, the xenogeneic NDM will induce host immune rejection leading to the transplantation failure. This study constructed the xenogeneic (porcine) NDM (xNDM) which carried the immunoregulator Rosiglitazone (xNDM-RSG), a synthetic highly selective agonist of peroxisome proliferator-activated receptor-gamma (PPAR gamma), evaluated xNDM's physical and chemical characterization, immunomodulatory properties, and its effect on the tissue regeneration. Results showed that the xNDM-RSG did not affect the proliferation and differentiation of odontogenic stem cells. In addition, the xNDM-RSG could also effectively decrease the expression of IL-1 and TNF alpha, and increase the expression of IL-10 and TGF beta to enable a favorable immunomodulation and promote the ligament-to-bone regeneration by PPAR gamma to induce the alternative activated macrophages (M2 macrophages) antagonizing classically activated macrophages (M1 macrophages). Meanwhile the xNDM-RSG obviously reduces the implants absorption and promotes the regenerated ligament-to-bone expressing the key proteins (ALP, OPN, DSP) which are relative to the native dental and bone. This study demonstrated that protein adsorption could aggravate the immune inflammatory reaction, whereas, xNDM-RSG could effectively control the host immune response to accelerate tissue reparation and regeneration by facilitating the macrophage polarization, which highlighted a new strategy for improving the transplantation survival of the artificial organ or tissue based on the xenogeneic decellularized biomaterials.