Neuronal differentiation of hair-follicle-bulge-derived stem cells co-cultured with mouse cochlear modiolus explants

Stem-cell-based repair of auditory neurons may represent an attractive therapeutic option to restore sensorineural hearing loss. Hair-follicle-bulge-derived stem cells (HFBSCs) are promising candidates for this type of therapy, because they (1) have migratory properties, enabling migration after transplantation, (2) can differentiate into sensory neurons and glial cells, and (3) can easily be harvested in relatively high numbers. However, HFBSCs have never been used for this purpose. We hypothesized that HFBSCs can be used for cell-based repair of the auditory nerve and we have examined their migration and incorporation into cochlear modiolus explants and their subsequent differentiation. Modiolus explants obtained from adult wild-type mice were cultured in the presence of EF1α-copGFP-transduced HFBSCs, constitutively expressing copepod green fluorescent protein (copGFP). Also, modiolus explants without hair cells were co-cultured with DCX-copGFP-transduced HFBSCs, which demonstrate copGFP upon doublecortin expression during neuronal differentiation. Velocity of HFBSC migration towards modiolus explants was calculated, and after two weeks, co-cultures were fixed and processed for immunohistochemical staining. EF1α-copGFP HFBSC migration velocity was fast: 80.5 ± 6.1 μm/h. After arrival in the explant, the cells formed a fascicular pattern and changed their phenotype into an ATOH1-positive neuronal cell type. DCX-copGFP HFBSCs became green-fluorescent after integration into the explants, confirming neuronal differentiation of the cells. These results show that HFBSC-derived neuronal progenitors are migratory and can integrate into cochlear modiolus explants, while adapting their phenotype depending on this micro-environment. Thus, HFBSCs show potential to be employed in cell-based therapies for auditory nerve repair

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.Transplantation and immunomodulatio

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

Transplantation and immunomodulatio