High titers of pre-existing adenovirus serotype-specific neutralizing antibodies in the host predict viral reactivation after allogeneic stem cell transplantation in children.

BACKGROUND: Human adenovirus (HAdV) infections are frequent in children after allogeneic stem cell transplantation (SCT) and may become fatal. Whether these infections occur through reactivation of endogenous virus or transmission via the graft remains a matter of debate. METHODS: In a cohort of 24 pediatric patients who received SCT, infections with 1 or more of 5 serotypes of HAdV (1, 2, 5, 6, and 31) were detected by culture. Neutralizing antibody (NAb) titers were measured in vitro by means of a virus neutralization assay. RESULTS: In 11 patients the infection was restricted to 1 site as demonstrated by culture only, and in 13 patients the HAdV infection was disseminated because plasma samples contained HAdV DNA. The 5 most commonly encountered HAdV serotypes caused 35 infectious episodes after SCT. Serum titers of NAb against these 5 serotypes of HAdV were measured before and after transplantation. High titers of NAb against a certain serotype in the recipient prior to SCT, reflecting previous infection, appeared to predispose for infection with the same serotype after SCT. In only 1 case of 41 independent samples of graft material, a very low level of HAdV DNA was detected. Antibody responses after SCT were detected in 21 of 35 infectious episodes. CONCLUSIONS: Together, these data suggest that adenoviral complications after SCT are caused by reactivation of endogenous persistent HAdV rather than by de novo infection from the donor or environment. This finding may offer a strategy of prophylactic treatment of high-risk patients before SCT to prevent infectious complications after allogeneic SCT.

Uncomplicated differentiation of stem cells into bipolar neurons and myelinating glia.

Epidermal neural crest stem cells (EPI-NCSCs), derived from the bulge of hair follicles, appear to be promising donor stem cell candidates. In the current work, EPI-NCSCs were harvested from rodents and humans. Isolation procedures revealed high levels of nestin-positive neural stem cells and the percentage of human neural stem cells (95+/-0.6%) is even higher than the percentage found in cultures of hair follicles from rodents (90+/-0.9%). Furthermore, differentiation of EPI-NCSCs into bipolar neurons, myelinating Schwann cells and oligodendrocytes occurred by applying a simple and straightforward method. Bipolar neurons could be obtained by culturing on a collagen matrix and are of great interest for auditory neuron regeneration since auditory neurons are bipolar. We propose that this type of stem cells, would make an excellent model for autologous transplantation and offers great potential for neural regeneration in diseases, such as Parkinson's and Alzheimer's disease.