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

PLoS One. 2013 Aug 5;8(8):e71412. doi: 10.1371/journal.pone.0071412. Print 2013.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Cells, Cultured
  • Chlorocebus aethiops
  • Cricetinae
  • Disease Susceptibility
  • Embryo, Mammalian
  • Female
  • Herpesviridae Infections / pathology
  • Herpesviridae Infections / virology*
  • Human Umbilical Vein Endothelial Cells / physiology
  • Humans
  • Mesenchymal Stem Cells / pathology
  • Mesenchymal Stem Cells / virology*
  • Placenta / pathology
  • Placenta / virology*
  • Pregnancy
  • Vero Cells

Grants and funding

This work was supported by Università di Bologna, Assegni di Ricerca, www.unibo.it; Fondi Ateneo per la Ricerca, Università di Ferrara, www.unife.it; Associazione Italiana per la Ricerca sui Virus, Bologna, www.airv.it; and Fondi attività di ricerca istituzionali, Università di Padova, www.unipd.it. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.