Persistence of Human Parvovirus B19 in Multipotent Mesenchymal Stromal Cells Expressing the Erythrocyte P antigen: Implications for Transplantation

Multipotent mesenchymal stromal cells (MSC) are used to improve the outcome of hematopoietic stem cell transplantation (HSCT) and in regenerative medicine. However, human MSC may harbor persistent viruses that may compromise their clinical benefit. Parvovirus B19, known to cause the childhood disease erythema infectiosum (“fifth disease”), can be hazardous to HSCT recipients due to development of a virus mediated severe pancytopenia. Retro spectively screened, 1 of 20 MSC from healthy donors contained B19 DNA. The donors exhibited a seroprevalence of anti-B19 IgG comparable to the reported normal level. Using flow cytometry, we found that human MSC (n=6) expressed the erythrocyte P antigen (also called globoside), reported as the B19 receptor, and Ku 80, a reported B19 co-receptor. After in vitro exposure to plasma derived from B19 viremic patients, MSC (n=3) were found positive for intracellular B19 proteins as determined by immunofluorescence. This demonstrates that MSC can be infected by B19. Further studies revealed that MSC could transmit B19 to bone marrow cells in vitro, suggesting that the virus can persist in the marrow stroma of healthy individuals. Two HSCT patients received the B19 positive MSC as treatment for graft-versus-host disease. Neither developed viremia nor symptomatic B19 infection, even though they where severely immunocompromised by means of subnormal Ig levels, low leukocyte counts and poor responses in mixed lymphocyte cultures. These results demonstrate for the first time that persistent B19 in MSC can infect hematopoietic cells and underscore the importance of monitoring B19 transmission by MSC products.