Journal
JOURNAL OF NEUROSURGERY
Volume 136, Issue 3, Pages 757-767Publisher
AMER ASSOC NEUROLOGICAL SURGEONS
DOI: 10.3171/2021.3.JNS203045
Keywords
mesenchymal stem cells; glioblastoma; brain tumor; oncolytic virus; oncology
Categories
Funding
- National Cancer Institute [1R01CA214749, 1R01CA247970, P30CA016672, 2P50CA127001]
- University of Texas MD Anderson Moon Shots Program
- Broach Foundation for Brain Cancer Research
- Elias Family Fund
- Priscilla and Jason Hiley Fund
- Baumann Family/CureFest Fund
- Jim and Pam Harris Fund
- Gene Pennebaker Brain Cancer Fund
- Schneider Memorial Cancer Research Fund
- Sweet Family Cancer Research Fund
- Dr. Marnie Rose Foundation
- Gold Family Memorial Fund
- Sorenson Foundation
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The study investigated the feasibility of obtaining bone marrow-derived human mesenchymal stem cells (BM-hMSCs) from patients with recurrent malignant glioma previously treated with marrow-toxic chemotherapy. Results showed that patient-derived BM-hMSCs (PD-BM-hMSCs) could effectively deliver oncolytic viruses and eradicate human gliomas in vitro and in vivo.
OBJECTIVE Delta-24-RGD is an oncolytic adenovirus that is capable of replicating in and killing human glioma cells. Although intratumoral delivery of Delta-24-RGD can be effective, systemic delivery would improve its clinical applica-tion. Bone marrow-derived human mesenchymal stem cells (BM-hMSCs) obtained from healthy donors have been investigated as virus carriers. However, it is unclear whether BM-hMSCs can be derived from glioma patients previously treated with marrow-toxic chemotherapy or whether such BM-hMSCs can deliver oncolytic viruses effectively. Herein, the authors undertook a prospective clinical trial to determine the feasibility of obtaining BM-hMSCs from patients with recurrent malignant glioma who were previously exposed to marrow-toxic chemotherapy. METHODS The authors enrolled 5 consecutive patients who had been treated with radiation therapy and chemothera-py. BM aspirates were obtained from the iliac crest and were cultured to obtain BM-hMSCs. RESULTS The patient-derived BM-hMSCs (PD-BM-hMSCs) had a morphology similar to that of healthy donor-derived BM-hMSCs (HD-BM-hMSCs). Flow cytometry revealed that all 5 cell lines expressed canonical MSC surface markers. Importantly, these cultures could be made to differentiate into osteocytes, adipocytes, and chondrocytes. In all cases, the PD-BM-hMSCs homed to intracranial glioma xenografts in mice after intracarotid delivery as effectively as HD-BM-hMSCs. The PD-BM-hMSCs loaded with Delta-24-RGD (PD-BM-MSC-D24) effectively eradicated human gliomas in vitro. In in vivo studies, intravascular administration of PD-BM-MSC-D24 increased the survival of mice harboring U87MG gliomas. CONCLUSIONS The authors conclude that BM-hMSCs can be acquired from patients previously treated with marrow-toxic chemotherapy and that these PD-BM-hMSCs are effective carriers for oncolytic viruses.
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