Abstract:
Cellular memory is a controversial concept representing the ability of cells to \"write and memorize\" stressful experiences via epigenetic operators. The progressive course of chronic, non-communicable diseases such as type 2 diabetes mellitus, cancer, and arteriosclerosis, is likely driven through an abnormal epigenetic reprogramming, fostering the hypothesis of a cellular pathologic memory. Accordingly, cultured diabetic and cancer patient-derived cells recall behavioral traits as when in the donor\'s organism irrespective to culture time and conditions. Here, we analyze the data of studies conducted by our group and led by a cascade of hypothesis, in which we aimed to validate the hypothetical existence and transmissibility of a cellular pathologic memory in diabetes, arteriosclerotic peripheral arterial disease, and cancer. These experiments were based on the administration to otherwise healthy animals of cell-free filtrates prepared from human pathologic tissue samples representative of each disease condition. The administration of each pathologic tissue homogenate consistently induced the faithful recapitulation of: (1) Diabetic archetypical changes in cutaneous arterioles and nerves. (2) Non-thrombotic arteriosclerotic thickening, collagenous arterial encroachment, aberrant angiogenesis, and vascular remodeling. (3) Pre-malignant and malignant epithelial and mesenchymal tumors in different organs; all evocative of the donor\'s tissue histopathology and with no barriers for interspecies transmission. We hypothesize that homogenates contain pathologic tissue memory codes represented in soluble drivers that \"infiltrate\" host\'s animal cells, and ultimately impose their phenotypic signatures. The identification and validation of the actors in behind may pave the way for future therapies.
摘要:
细胞记忆是一个有争议的概念,代表细胞通过表观遗传算子“书写和记忆”压力经历的能力。慢性的渐进过程,非传染性疾病,如2型糖尿病,癌症,和动脉硬化,可能是由异常的表观遗传重编程驱动的,促进细胞病理记忆的假设。因此,培养的糖尿病和癌症患者来源的细胞回忆起在供体生物体中的行为特征,而与培养时间和条件无关。这里,我们分析了我们小组进行的一系列假设的研究数据,我们旨在验证糖尿病中细胞病理记忆的假设存在和传播性,动脉硬化性外周动脉疾病,和癌症。这些实验基于将从代表每种疾病状况的人病理组织样品制备的无细胞滤液施用于其他健康动物。每种病理组织匀浆的给药一致地引起以下方面的忠实回顾:(1)皮肤小动脉和神经的糖尿病典型变化。(2)非血栓性动脉硬化性增厚,胶原动脉侵犯,异常血管生成,和血管重塑。(3)不同器官的恶性前和恶性上皮和间质肿瘤;都反映了供体的组织病理学,并且没有种间传播的障碍。我们假设匀浆含有以可溶性驱动因子表示的病理组织记忆代码,这些驱动因子“渗入”宿主的动物细胞,并最终强加它们的表型特征。识别和验证背后的参与者可能为未来的治疗铺平道路。