Transmissible Diseases Department, American Red Cross Holland Laboratory, Rockville, MD 20855, USA.
Transfusion. 2011 Aug;51(8):1755-68. doi: 10.1111/j.1537-2995.2010.03041.x. Epub 2011 Feb 8.
The possible risk of iatrogenic transmissible spongiform encephalopathies (TSEs, prion diseases) from transplantation of marrow-derived mesenchymal stem cells (MSCs) is uncertain. While most cell lines resist infection, a few propagate TSE agents.
We generated MSC-like (MSC-L) cell cultures from bone marrow (BM) of mice inoculated with the human-derived Fukuoka-1 (Fu) strain of TSE agent. Cultured cells were characterized for various markers and cellular prion protein (PrP(C) ) by fluorescence-activated cell sorting and for PrP(C) and its pathologic TSE-associated form (PrP(TSE) ) by Western blotting (WB). Cell cultures were tested for their susceptibility to infection with Fu in vitro. The infectivity of one Fu-infected cell culture was assayed in mice.
BM cells from Fu-infected mice expressed neither PrP(C) nor PrP(TSE) after 3 days in culture as demonstrated by WB. Cells adherent to plastic and maintained under two different culture conditions became spontaneously immortalized and began to express PrP(C) at about the same time. One culture became transformed shortly after exposure to Fu in vitro and remained persistently infected, continuously generating PrP(TSE) through multiple passages; the infectivity of cultured cells was confirmed by intracerebral inoculation of lysates into mice. Both persistently TSE-infected and uninfected cells expressed a number of typical MSC markers.
BM-derived MSC-L cells of mice became persistently infected with the Fu agent under certain conditions in culture-conditions that differ substantially from those currently used to develop investigational human stem cell therapies.
骨髓来源的间充质干细胞（MSCs）移植可能存在医源性传播海绵状脑病（TSEs，朊病毒病）的风险，但尚不确定。虽然大多数细胞系可以抵抗感染，但有少数细胞系可以传播 TSE 病原体。
我们从接种了人类源性福冈-1（Fu）株 TSE 病原体的小鼠骨髓（BM）中生成 MSC 样（MSC-L）细胞培养物。通过荧光激活细胞分选对培养细胞进行各种标志物和细胞朊蛋白（PrP(C)）的鉴定，并通过 Western blot（WB）对 PrP(C)及其病理性 TSE 相关形式（PrP(TSE)）进行鉴定。体外检测细胞培养物对 Fu 感染的敏感性。在小鼠中检测了一个 Fu 感染细胞培养物的感染性。
WB 显示，Fu 感染小鼠的 BM 细胞在培养 3 天后既不表达 PrP(C)也不表达 PrP(TSE)。贴壁于塑料并在两种不同培养条件下维持的细胞自发永生化，并在大约相同的时间开始表达 PrP(C)。一个培养物在体外暴露于 Fu 后不久就发生转化，并持续感染，通过多次传代不断产生 PrP(TSE)；通过将培养细胞的裂解物脑内接种到小鼠中证实了其感染性。持续感染 TSE 的细胞和未感染的细胞均表达了许多典型的 MSC 标志物。
在某些培养条件下，来自小鼠的 BM 来源的 MSC-L 细胞持续感染 Fu 病原体，这些条件与目前用于开发人类干细胞治疗的研究条件有很大不同。
