Department of Oncology, Haematology and Laboratory Medicine, Operative Unit of Microbiology, A. O-U. di Bologna Policlinico S. Orsola-Malpighi, Bologna, Italy.
PLoS One. 2013 Aug 5;8(8):e71412. doi: 10.1371/journal.pone.0071412. Print 2013.
Fetal membranes (FM) derived mesenchymal stromal/stem cells (MSCs) are higher in number, expansion and differentiation abilities compared with those obtained from adult tissues, including bone marrow. Upon systemic administration, ex vivo expanded FM-MSCs preferentially home to damaged tissues promoting regenerative processes through their unique biological properties. These characteristics together with their immune-privileged nature and immune suppressive activity, a low infection rate and young age of placenta compared to other sources of SCs make FM-MSCs an attractive target for cell-based therapy and a valuable tool in regenerative medicine, currently being evaluated in clinical trials. In the present study we investigated the permissivity of FM-MSCs to all members of the human Herpesviridae family, an issue which is relevant to their purification, propagation, conservation and therapeutic use, as well as to their potential role in the vertical transmission of viral agents to the fetus and to their potential viral vector-mediated genetic modification. We present here evidence that FM-MSCs are fully permissive to infection with Herpes simplex virus 1 and 2 (HSV-1 and HSV-2), Varicella zoster virus (VZV), and Human Cytomegalovirus (HCMV), but not with Epstein-Barr virus (EBV), Human Herpesvirus-6, 7 and 8 (HHV-6, 7, 8) although these viruses are capable of entering FM-MSCs and transient, limited viral gene expression occurs. Our findings therefore strongly suggest that FM-MSCs should be screened for the presence of herpesviruses before xenotransplantation. In addition, they suggest that herpesviruses may be indicated as viral vectors for gene expression in MSCs both in gene therapy applications and in the selective induction of differentiation.
胎儿膜（FM）衍生的间充质基质/干细胞（MSCs）在数量、扩增和分化能力方面均高于成人组织（包括骨髓）中获得的 MSC。在全身给药后，体外扩增的 FM-MSCs 优先归巢至受损组织，通过其独特的生物学特性促进再生过程。这些特性以及它们的免疫特权性质和免疫抑制活性、与其他 SC 来源相比，FM-MSCs 的感染率较低、胎盘较年轻，使得 FM-MSCs 成为细胞治疗的有吸引力的靶标，并且是再生医学中有价值的工具，目前正在临床试验中进行评估。在本研究中，我们研究了 FM-MSCs 对人类疱疹病毒科（Herpesviridae family）所有成员的允许性，这与它们的纯化、繁殖、保存和治疗用途以及它们在病毒剂垂直传播到胎儿中的潜在作用以及它们作为病毒载体介导的遗传修饰的潜在作用有关。我们在这里提供的证据表明，FM-MSCs 完全允许感染单纯疱疹病毒 1 和 2（HSV-1 和 HSV-2）、水痘带状疱疹病毒（VZV）和人类巨细胞病毒（HCMV），但不允许感染 EBV、人类疱疹病毒 6、7 和 8（HHV-6、7、8），尽管这些病毒能够进入 FM-MSCs 并发生短暂的、有限的病毒基因表达。因此，我们的研究结果强烈表明，在异种移植前，应筛选 FM-MSCs 中是否存在疱疹病毒。此外，它们表明疱疹病毒可以作为 MSC 中基因表达的病毒载体，既可以用于基因治疗应用，也可以用于选择性诱导分化。
