Mesenchymal stem cell-like properties of CD133(+) glioblastoma-initiating cells

Glioblastoma is composed of dividing tumor cells, stromal cells and tumor initiating CD133(+) cells. Recent reports have discussed the origin of the glioblastoma CD133(+) cells and their function in the tumor microenvironment. The present work sought to investigate the multipotent and mesenchymal properties of primary highly purified human CD133(+) glioblastoma-initiating cells. To accomplish this aim, we used the following approaches: i) generation of tumor subspheres of CD133(+) selected cells from primary cell cultures of glioblastoma; ii) analysis of the expression of pluripotency stem cell markers and mesenchymal stem cell (MSC) markers in the CD133(+) glioblastoma-initiating cells; iii) side-by-side ultrastructural characterization of the CD133(+) glioblastoma cells, MSC and CD133(+) hematopoietic stem cells isolated from human umbilical cord blood (UCB); iv) assessment of adipogenic differentiation of CD133(+) glioblastoma cells to test their MSC-like in vitro differentiation ability; and v) use of an orthotopic glioblastoma xenograft model in the absence of immune suppression. We found that the CD133(+) glioblastoma cells expressed both the pluripotency stem cell markers (Nanog, Mush-1 and SSEA-3) and MSC markers. In addition, the CD133(+) cells were able to differentiate into adipocyte-like cells. Transmission electron microscopy (TEM) demonstrated that the CD133(+) glioblastoma-initiating cells had ultrastructural features similar to those of undifferentiated MSCs. In addition, when administered in vivo to non-immunocompromised animals, the CD133(+) cells were also able to mimic the phenotype of the original patient's tumor. In summary, we showed that the CD133(+) glioblastoma cells express molecular signatures of MSCs, neural stem cells and pluripotent stem cells, thus possibly enabling differentiation into both neural and mesodermal cell types

Metástasis difusa de la médula ósea en un astrocitoma cerebeloso de alto grado. Un caso clínico / Diffuese bone marrow metastasis in cerebellar high grade astrocytoma. A case report

Resumen. Introducción. El astrocitoma cerebeloso de alto grado es poco frecuente. La localización cerebelosa, aunque más proclive a presentar diseminación del líquido cefalorraquídeo, no está especialmente relacionada con la aparición de metástasis extracraneales, que también son poco frecuentes en los gliomas supratentoriales malignos. Caso clínico. Varón de 46 años con astrocitoma anaplásico cerebeloso, que padeció pancitopenia debido a metástasis extensas de la médula ósea. Conclusión. Las metástasis extraneurales de gliomas cerebrales son poco frecuentes, y la extensión a la médula ósea confiere un pronóstico muy malo en estos pacientes. La mejora esperada en la supervivencia en pacientes con gliomas debido a la combinación de tratamientos más eficaces puede conducir a un aumento de la incidencia de esta presentación poco frecuente, justificandoun seguimiento más riguroso de las manifestaciones sistémicas (AU)

Summary. Introduction. Cerebellar high-grade astrocytoma is uncommon. Although more prone to present cerebrospinal fluid dissemination, the cerebellar location is not particularly related to the occurrence of extra-cranial metastases, which are also unusual in supratentorial malignant gliomas. Case report. A 46 year-old man with cerebellar anaplastic astrocytoma who developed pancytopenia due to extensive bone marrow metastases. Conclusion. Extraneural metastases of brain gliomas are rare and the spread to the bone marrow confers an extremely poor prognosis for these patients. The expected improvement in glioma patients’ survival due to the combination of more efficient therapies may lead to an increased incidence of this uncommon presentation, justifying a more rigorous follow-up of systemic manifestations (AU)