ROCK Inhibition Facilitates In Vitro Expansion of Glioblastoma Stem-Like Cells
نویسندگان
چکیده
Due to their stem-like characteristics and their resistance to existing chemo- and radiation therapies, there is a growing appreciation that cancer stem cells (CSCs) are the root cause behind cancer metastasis and recurrence. However, these cells represent a small subpopulation of cancer cells and are difficult to propagate in vitro. Glioblastoma is an extremely deadly form of brain cancer that is hypothesized to have a subpopulation of CSCs called glioblastoma stem cells (GSCs; also called brain tumor initiating cells, BTICs). We propose the use of selective Rho-kinase (ROCK) inhibitors, Y-27632 and fasudil, to promote GSC/BTIC-like cell survival and propagation in vitro. ROCK inhibitors have been implicated in suppressing apoptosis, and it was hypothesized that they would increase the number of GSC/BTIC-like cells grown in vitro and improve cloning efficiencies. Indeed, our data demonstrate that transient and continuous supplementation of non-toxic concentrations of Y-27632 and fasudil inhibited apoptosis, enhanced the cells' ability to form spheres, and increased stem cell marker expressing GSC/BTIC-like cell subpopulation. Our data indicated that pharmacological and genetic (siRNA) inhibitions of the ROCK pathway facilitates in vitro expansion of GSC/BTIC-like cells. Thus, ROCK pathway inhibition shows promise for future optimization of CSC culture media.
منابع مشابه
Human Mesenchymal Stem Cells and Their, Clinical Aapplication
There are two main categories for stem cells a cording to their origin: Embryonic Stem Cells and Adult Stem Cell. Mesenchymal stem cell, supporting hematopoetic stem cells in bone marrow, can regenerate tissues such as bone, cartilage, muscle, tendon and fatty tissue. These cells were recognized for the first time by Friedenstein and Petrokova who could isolate theme from rat bone marrow.Mesenc...
متن کاملComparison of Neonatal and Adult Mice-derived Sertoli Cells in Support of Expansion of Mouse Spermatogonial Stem Cells In vitro
متن کامل
Nogo receptor blockade enhances subventricular zone’s stem cells proliferation and differentiation in demyelination context
Introduction: Nogo-A and Nogo receptor (NgR) are expressed in the subventricular zone (SVZ) stem cells. NgR plays critical inhibitory roles in axonal regeneration and remyelination. However, the role of NgR in SVZ niche behaviors in demyelination context is still uncertain. Here we investigated the effects of NgR inhibition on SVZ niche reaction in a local model of demyelination in adult mouse ...
متن کاملThe Validated Embryionic Stem Cell Test to Predict Embryotoxicityinvitro
Backgrounds: A straight-forward way to identify whether a drug or environmental chemical can be harmful to unborn baby is to evaluate its effect on laboratory animals. All invivo methods need large number of animal and are therefore time consuming and expensive. However, the thousands of chemicals in need of testing, to reduce the spending of live animals, an assortment of in vitro assays has ...
متن کاملExpansion of Non-Enriched Cord Blood Stem/Progenitor Cells CD34+ CD38- Using Liver Cells
Many investigators have used xenogeneic, especially murine stromal cells and fetal calf serum to maintain and expand human stem cells. The proliferation and expansion of human hematopoietic stem cells in ex vivo culture were examined with the goal of generating a suitable protocol for expanding hematopoietic stem cells for patient transplantation. Using primary fetal liver cells, we established...
متن کامل