Susceptibility of human placenta derived mesenchymal stromal/stem cells to human herpesviruses infection.

Susceptibility of human placenta derived mesenchymal stromal/stem cells to human herpesviruses infection.
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DOI:
10.1371/journal.pone.0071412
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Ripalti A
Ripalti A
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Avanzi S;Leoni V;Rotola A;Alviano F;Solimando L;Lanzoni G;Bonsi L;Di Luca D;Marchionni C;Alvisi G;Ripalti A

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与从成人组织(包括骨髓)获得的那些相比,胎儿膜(FM)来源的间充质基质/干细胞(MSC)在数量、扩增和分化能力上更高。在全身给药后,离体扩增的FM-MSC优先归巢受损组织,通过其独特的生物学特性促进再生过程。这些特征连同它们的免疫特权性质和免疫抑制活性、与其他SC来源相比的低感染率和胎盘的年轻年龄使FM-MSC成为基于细胞的治疗的有吸引力的靶点和再生医学中的有价值的工具,目前正在临床试验中进行评估。在本研究中,我们调查了FM-MSCs对人类疱疹病毒科所有成员的感染,这是一个与其纯化、繁殖、保存和治疗用途相关的问题,以及它们在病毒因子垂直传播至胎儿中的潜在作用和它们潜在的病毒载体介导的遗传修饰。我们在此提供的证据表明,FM-MSC完全允许单纯疱疹病毒1型和2型(HSV-1和HSV-2)、水痘带状疱疹病毒(VZV)和人巨细胞病毒(HCMV)感染,但不允许EB病毒(EBV)、人疱疹病毒-6,7和8型(HHV-6,7,8)感染,尽管这些病毒能够进入FM-MSC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建议,FM-MSCs应进行筛选,在异种移植前疱疹病毒的存在。此外,他们建议疱疹病毒可作为病毒载体用于基因治疗应用和选择性诱导分化中的MSC中的基因表达。
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.
DOI: 10.1006/viro.1999.9875
发表时间: 1999-09-15
期刊: VIROLOGY
影响因子: 3.7
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DOI: 10.1111/j.1365-2141.2008.07492.x
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DOI: 10.1128/jvi.00669-09
发表时间: 2009-09-15
影响因子: 5.4
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DOI: 10.1038/sj.cr.7310043
发表时间: 2006-04-01
期刊: CELL RESEARCH
影响因子: 44.1
作者:
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