multipotent stem cells

first paper what i'm going to cover is thervery primitive research about isolation and identification of a cancer stem cell in humanbrain tumors. nowadays, heterogeneity and diversity of cells in cancer tissue is wellknown to researchers, but even before decades ago, understanding about tumor environmentwas not that clear. this paper suggested early ideas for presence of essenstial sub populationin brain tumor, which has multipotency, capacity for multi-lineage differentiation and sphere-formingability. tumor-associated environment including fibroblast,endothelial, tumor-associated blood vessels and other surrounding components helps cancercells to mantain tumor-friendly environment or metastasized to other region. among thesepopulation, essential subpopulation named

cancer stem cell play key role for heterogeneityof tumor tissue. due to its importance, efforts to identifyand isolate those population have benn continued. as you can see in the cartoon, various approcheshave been proposed, and each method focuses on certain properties of the cancer stem cells.for example, aldh method is application of high aldh expression of high in progenitoror stem cells. identification of brain tumor stem cell however,changed paradigm of brain tumor treatment. as we can see in the picture, conventionalradiation therapy has limitation due to the radiation resistance of cancer stem cell orcd133 positive cells, but pre-treatment of the growth factor like bone morphogeneticproteins induces loss of stemness of cd133

positive cells, and makes the following treatmentmore effective. back to the paper, now let's take a closerlook of cancer stem cell isolation. in this paper, they used various types of primarycancer cells. first figure showed there were various cancer cells that forming spheresin vitro. from the left column, medulloblastoma, pilocytic astrocytoma, ependymoma and gangliogliomacells are shown. first row shows in vitro image of each primary cancer cells, secondrow is tumor sphere image of nestin and cd133 stained. third row shows differentiated cellseach cells, also nestin and cd133 stained. next, they showed sphere forming cells exhibitsincresed self renewal potential compared with control. medulloblastoma cells, which showedrelatively high secondary sphere forming capacity,

also showed enhanced self renewal potentialat limiting dilution assay. c,d,e shows secondary tumor spheres still expressing nestin andcd133. they also observed that tumor sphere cellsexhibit increased proliferation consistent with histopathologic mitotic indices. tumorstemcells from dissociated medulloblastoma spheres showed excessive degree of cell proliferationthan pilocytic astrocytoma or normal neurosphere cells.they also checked tumor sphere cells can differentiate into other immunophenotype, and confrimedit with various markers. tumor sphere cell marker cd133 and nestin, was no longer higlyexpressed by the cells once they differentiated into certain phenotypes. instead, differentiatedcell showed altered marker expression pattern.

in case of pilocytic astrocytoma, differentiatedcells' cd133 and nestin expression pattern dramatically decreased, and gfap expressionincreased abruptly. medullobalstoma sphere cells showed same change in expression pattern,too. since they found cd133 positive cells havedistinct properties compared to others, they indentified the general feature of the cd133positive cells. similar to previous findings, cd133 positive cells showed marked stem cellactivity. after they sorted the cd133 positive primary medulloblastoma cells with flow cytometry,tumor sphere formation and proliferation capacity was checked, and they found there's huge differencebetween cd133 positive and cd133 negative cells.difference among normal neural stem cells,

cd133 positive cancer cells and cd133 negativecancner cells is also investigated. huge difference between normal stem cells and cancer cellwas excessive expression of beta tubulin in cancer cells. authors suggested that thisdifference is originated by genetic abnormality based on their finding that tumor sphere cellsshowed abnormal karyotype including loss of chromosome 10, 16 and gain of chromosome 18.this paper provided general and primary view for brain tumor stem cells, cited by manyother researchers numerous times. although the conocept of cancer stem cell is stillcontroversial in some cases, it is clear that certain population in tumor cells are responsiblefor various stem-like properties of the tumor tissue.