Cancer cell reprogramming based on aptamers with antiproliferative properties in combination with small molecules that are used for conversion iPSCs into neurons represents a new approach to reduce the probability of glioblastoma recurrence and tumor resistance to therapy. In this research we tested several combinations of factors on whole cell cultures, derived from tumor tissue after surgical resection, and on cell cultures divided in CD133 enriched and depleted populations, as CD133 marker is believed to be characteristic for glioblastoma stem cells. We showed that CD133+ and CD133- cells have a different response to tested combinations of factors and CD133-positive cells are more stable and possess stemness properties. Thus, affecting these cells will lead to decrease of therapy resistance. Moreover, we found a combination of factors that is able to inhibit proliferation of both CD133+ and CD133- cells. Our results reveal a promising strategy to improve treatment of patients with glioblastoma.