TY - JOUR
T1 - Characterization of patient-derived bone marrow human mesenchymal stem cells as oncolytic virus carriers for the treatment of glioblastoma
AU - Shimizu, Yuzaburo
AU - Gumin, Joy
AU - Gao, Feng
AU - Hossain, Anwar
AU - Shpall, Elizabeth J.
AU - Kondo, Akihide
AU - Kerrigan, Brittany C.Parker
AU - Yang, Jing
AU - Ledbetter, Daniel
AU - Fueyo, Juan
AU - Gomez-Manzano, Candelaria
AU - Lang, Frederick F.
N1 - Funding Information:
lications, and David Wildrick, PhD, Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, for their editorial assistance. This study was supported by the National Cancer Institute (grants nos. 1R01CA214749, 1R01CA247970, P30CA016672, and 2P50CA127001), The University of Texas MD Anderson Moon Shots Program, The Broach Foundation for Brain Cancer Research, The Elias Family Fund, The Priscilla and Jason Hiley Fund, The Baumann Family/CureFest Fund, The Jim and Pam Harris Fund, The Gene Pennebaker Brain Cancer Fund, The Schneider Memorial Cancer Research Fund, The Sweet Family Cancer Research Fund, The Dr. Marnie Rose Foundation, The Gold Family Memorial Fund, and The Sorenson Foundation (all to F.F.L.).
Publisher Copyright:
© AANS 2022.
PY - 2022/3
Y1 - 2022/3
N2 - 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 HDBM- 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 marrowtoxic chemotherapy and that these PD-BM-hMSCs are effective carriers for oncolytic viruses.
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 HDBM- 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 marrowtoxic chemotherapy and that these PD-BM-hMSCs are effective carriers for oncolytic viruses.
KW - brain tumor
KW - glioblastoma
KW - mesenchymal stem cells
KW - oncology
KW - oncolytic virus
UR - http://www.scopus.com/inward/record.url?scp=85126710435&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85126710435&partnerID=8YFLogxK
U2 - 10.3171/2021.3.JNS203045
DO - 10.3171/2021.3.JNS203045
M3 - Article
C2 - 34450587
AN - SCOPUS:85126710435
SN - 0022-3085
VL - 136
SP - 757
EP - 767
JO - Journal of neurosurgery
JF - Journal of neurosurgery
IS - 3
ER -