title: Mesenchymal stem cells are susceptible to human herpesviruses, but viral DNA cannot be detected in the healthy seropositive individual.
abstract: Allogeneic stem cell transplantation is often complicated by reactivation of herpesviruses. Mesenchymal stem cells (MSC) are immunomodulatory and may be used to treat graft-versus-host disease. We investigated if herpesviruses infect and can be transmitted by MSC, and if MSC suppress immune responses to various infectious agents. Mesenchymal stem cells from healthy seropositive donors were evaluated with polymerase chain reaction for the most common herpesviruses: cytomegalovirus (CMV), herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2, Epstein-Barr virus (EBV) and varicella zoster virus. The cytopathological effect (CPE) was investigated and viral antigens analyzed by immunofluorescence after in vitro exposure to CMV, HSV-1 and EBV. We also studied MSC effect on lymphocyte stimulation induced by various infectious agents. No viral DNA could be detected in MSC isolated from healthy seropositive individuals. However, a CPE was noted and intracellular viral antigens detected after infection in vitro by CMV and HSV-1, but not by EBV. The CMV and HSV-1 infections were productive. Lymphocyte proliferation by herpesviruses, candida mannan and protein A from Staphylococcus aureus was suppressed by MSC. The data indicate that the risk of herpesvirus transmission by transplantation of MSC from healthy seropositive donors is low. However, MSC may be susceptible to infection if infused in a patient with CMV or HSV-1 viremia. MSC transplantation may compromise the host's defense against infectious agents.
authors.affiliation: Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, SE-141 86 Stockholm, Sweden. mikael.sundin@ki.se
authors.forename: M
authors.initials: M
authors.lastname: Sundin
authors.forename: C
authors.initials: C
authors.lastname: Orvell
authors.forename: I
authors.initials: I
authors.lastname: Rasmusson
authors.forename: B
authors.initials: B
authors.lastname: Sundberg
authors.forename: O
authors.initials: O
authors.lastname: Ringdén
authors.forename: K
authors.initials: K
authors.lastname: Le Blanc
mesh_terms: D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000302:isolation & purification; D002353:Carrier State / Q000276:immunology / Q000821:virology; D003587:Cytomegalovirus / Q000472:pathogenicity; D003588:Cytopathogenic Effect, Viral; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D006564:Herpesviridae / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification / Q000472:pathogenicity*; D006566:Herpesviridae Infections / Q000276:immunology / Q000635:transmission / Q000821:virology; D018259:Herpesvirus 1, Human / Q000472:pathogenicity; D014645:Herpesvirus 3, Human / Q000472:pathogenicity; D004854:Herpesvirus 4, Human / Q000472:pathogenicity; D006801:Humans; D066298:In Vitro Techniques; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects; D059630:Mesenchymal Stem Cells / Q000821:virology*; D014019:Tissue Donors
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D004279:DNA, Viral