STEM-02. CHARACTERIZATION OF PATIENT-DERIVED BONE MARROW MESENCHYMAL STEM CELLS AS VIRUS CARRIERS FOR THE TREATMENT OF GLIOBLASTOMA

Abstract

Delta-24-RGD is an oncolytic adenovirus that is capable of replicating in and lysing human glioma cells. Although intratumoral delivery of Delta-24- RGD can be effective, systemic delivery would improve its clinical application. Bone marrow human mesenchymal stem cells (BM-hMSCs) derived from normal healthy donors have been investigated as virus carriers. However, it is not clear whether BM-hMSCs can be derived from patients with gliomas previously treated with marrow-toxic chemotherapy and whether such BM-hMSCs can deliver oncolytic viruses as effectively as BM-hMSCs from normal donors. In order to determine the feasibility of obtaining BMMSCs from patients with recurrent malignant glioma who had been exposed to marrow-toxic chemotherapy, we undertook a prospective clinical trial evaluating the ability of obtaining BM-MSCs from patients with recurrent gliomas. We enrolled 5 consecutive patients who had been previously treated with radiation therapy and chemotherapy and who were undergoing surgical resection for their recurrent glioma. BM aspirates were obtained from the iliac crest of each patient. Aspirates were cultured to obtain hMSCs. By passage 3, the patient derived BM-hMSCs (PD-hMSCs) cells had the morphology of normal BM-hMSCs. Flow cytometry revealed that all 5 cell lines expressed canonical surface markers characteristic of normal BM-hMSCs (positive for CD105, CD73, and CD90 and negative for CD45, CD34, and CD11b). Importantly, all 5 PD-hMSC cultures could be differentiated into osteocytes, adipocytes, and chondrocytes. In all cases, the PD-hMSCs homed to intracranial glioma xenografts in mice after intracarotid delivery as effectively as normal BM-hMSCs. PD-hMSCs could be loaded with Delta-24- RGD (PD-MSC-D24) and effectively killed human gliomas in vitro and in vivo. Specifically, intravascular administration of PD-hMSC-D24 increased the survival of mice harboring U87 gliomas. We conclude that BM-hMSCs can be acquired from patients previously treated with marrow-toxic chemotherapy and that these PD-hMSCs are effective vehicles for delivering oncolytic viruses.