PMID- 34450587 OWN - NLM STAT- MEDLINE DCOM- 20220411 LR - 20230616 IS - 1933-0693 (Electronic) IS - 0022-3085 (Print) IS - 0022-3085 (Linking) VI - 136 IP - 3 DP - 2022 Mar 1 TI - Characterization of patient-derived bone marrow human mesenchymal stem cells as oncolytic virus carriers for the treatment of glioblastoma. PG - 757-767 LID - 10.3171/2021.3.JNS203045 [doi] LID - 2021.3.JNS203045 AB - 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 application. 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 chemotherapy. 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. FAU - Shimizu, Yuzaburo AU - Shimizu Y AD - Departments of1Neurosurgery. AD - 4Brain Tumor Center, The University of Texas MD Anderson Cancer Center, Houston, Texas; and. AD - 5Department of Neurosurgery, Juntendo University School of Medicine, Tokyo, Japan. FAU - Gumin, Joy AU - Gumin J AD - Departments of1Neurosurgery. AD - 4Brain Tumor Center, The University of Texas MD Anderson Cancer Center, Houston, Texas; and. FAU - Gao, Feng AU - Gao F AD - Departments of1Neurosurgery. AD - 4Brain Tumor Center, The University of Texas MD Anderson Cancer Center, Houston, Texas; and. FAU - Hossain, Anwar AU - Hossain A AD - Departments of1Neurosurgery. AD - 4Brain Tumor Center, The University of Texas MD Anderson Cancer Center, Houston, Texas; and. FAU - Shpall, Elizabeth J AU - Shpall EJ AD - 2Stem Cell Transplantation, and. FAU - Kondo, Akihide AU - Kondo A AD - 5Department of Neurosurgery, Juntendo University School of Medicine, Tokyo, Japan. FAU - Parker Kerrigan, Brittany C AU - Parker Kerrigan BC AD - Departments of1Neurosurgery. AD - 4Brain Tumor Center, The University of Texas MD Anderson Cancer Center, Houston, Texas; and. FAU - Yang, Jing AU - Yang J AD - Departments of1Neurosurgery. AD - 4Brain Tumor Center, The University of Texas MD Anderson Cancer Center, Houston, Texas; and. FAU - Ledbetter, Daniel AU - Ledbetter D AD - Departments of1Neurosurgery. AD - 4Brain Tumor Center, The University of Texas MD Anderson Cancer Center, Houston, Texas; and. FAU - Fueyo, Juan AU - Fueyo J AD - 3Neuro-Oncology, and. AD - 4Brain Tumor Center, The University of Texas MD Anderson Cancer Center, Houston, Texas; and. FAU - Gomez-Manzano, Candelaria AU - Gomez-Manzano C AD - 3Neuro-Oncology, and. AD - 4Brain Tumor Center, The University of Texas MD Anderson Cancer Center, Houston, Texas; and. FAU - Lang, Frederick F AU - Lang FF AD - Departments of1Neurosurgery. AD - 4Brain Tumor Center, The University of Texas MD Anderson Cancer Center, Houston, Texas; and. LA - eng PT - Clinical Trial PT - Journal Article DEP - 20210827 PL - United States TA - J Neurosurg JT - Journal of neurosurgery JID - 0253357 RN - 0 (Oligopeptides) SB - IM MH - Animals MH - Bone Marrow MH - *Glioblastoma/pathology/therapy MH - *Glioma/pathology MH - Humans MH - *Mesenchymal Stem Cells/pathology MH - Mice MH - Neoplasm Recurrence, Local/pathology MH - Oligopeptides MH - *Oncolytic Viruses MH - Prospective Studies PMC - PMC10193507 OTO - NOTNLM OT - brain tumor OT - glioblastoma OT - mesenchymal stem cells OT - oncology OT - oncolytic virus COIS- Drs. Lang, Fueyo, and Gomez-Manzano are patent holders of Delta-24-RGD, which has been licensed to DNATrix, Inc. Drs. Fueyo and Gomez-Manzano are consultants for, receive royalties from, and hold patents with DNATrix, Inc. Dr. Lang holds a patent with DNATrix, Inc. EDAT- 2021/08/28 06:00 MHDA- 2022/04/12 06:00 PMCR- 2021/08/27 CRDT- 2021/08/27 20:30 PHST- 2020/08/08 00:00 [received] PHST- 2021/03/04 00:00 [accepted] PHST- 2021/08/28 06:00 [pubmed] PHST- 2022/04/12 06:00 [medline] PHST- 2021/08/27 20:30 [entrez] PHST- 2021/08/27 00:00 [pmc-release] AID - 2021.3.JNS203045 [pii] AID - 10.3171/2021.3.JNS203045 [doi] PST - epublish SO - J Neurosurg. 2021 Aug 27;136(3):757-767. doi: 10.3171/2021.3.JNS203045. Print 2022 Mar 1.