Akimov Sergey, Vasilyeva Irina, Yakovleva Oksana, McKenzie Carroll, Cervenakova Larisa
Transmissible Diseases Department, Holland Laboratory, American Red Cross, 15601 Crabbs Branch Way, Rockville, MD 20855, USA.
Folia Neuropathol. 2009;47(2):205-14.
Transmission of transmissible spongiform encephalopathies (TSEs)/prion diseases through transplantation of bone marrow (BM) has never been reported in humans. However, the use of fetal bovine serum in current protocols for generating mesenchymal stem cells (MSCs) carries the risk of iatrogenic spread. We developed a cell model from murine BM-derived MSCs and tested its susceptibility to Fukuoka-1 (Fu) strain of TSEs. The adherent cells expressed significant levels of normal prion protein, PrPC, at the time when they became immortalized. The cell culture underwent spontaneous transformation following inoculation with Fu-infected brain homogenate and became persistently infected after reinoculation with Fu agent. Extensive analysis of the original and two Fu-exposed cell cultures revealed a phenotype characteristic of MSCs with a majority of cells being positive for stem cell antigen, Sca-1. Taken together, our results demonstrate that BM-derived MSCs can be infected with TSE agents under certain conditions ex vivo. Comprehensive studies should be undertaken to address the safety of cell-based therapies in regard to iatrogenic transmission of TSEs. BM-derived cell cultures can be used for studies of molecular mechanisms underlying the cells' susceptibility to various strains of TSEs, their propagation ex vivo, and for screening of potential anti-TSEs therapeutics.
通过骨髓（BM）移植传播可传播性海绵状脑病（TSEs）/朊病毒疾病在人类中从未有过报道。然而，目前用于生成间充质干细胞（MSCs）的方案中使用胎牛血清存在医源性传播的风险。我们从小鼠BM来源的MSCs建立了一个细胞模型，并测试了其对TSEs福冈-1（Fu）株的易感性。贴壁细胞在永生化时表达了显著水平的正常朊病毒蛋白PrPC。细胞培养物在用Fu感染的脑匀浆接种后发生自发转化，并在用Fu制剂再次接种后持续感染。对原始细胞培养物和两个暴露于Fu的细胞培养物进行的广泛分析显示出MSCs的表型特征，大多数细胞对干细胞抗原Sca-1呈阳性。综上所述，我们的结果表明，BM来源的MSCs在体外某些条件下可被TSE病原体感染。应进行全面研究以解决基于细胞的疗法在TSEs医源性传播方面的安全性问题。BM来源的细胞培养物可用于研究细胞对各种TSEs毒株易感性的分子机制、它们在体外的传播以及筛选潜在的抗TSEs治疗方法。
