Table 2.

Summary of preclinical trails using stem cells for oncolytic virotherapy treatments. Studies investigating mesenchymal stem cells are listed first, followed by studies examining neural stem cells. The type of virus loaded and cancer treated are catalogued. Results and citation of each preclinical trial are also included.

Type of Stem Cell Carrier	Species of Origin	Type of Virus	Type of Cancer Treated	Result	Reference
Bone marrow-derived mesenchymal stromal cells	Human	Oncolytic Adenovirus	Pancreatic	Capsid modification leads to enhancement of therapeutic viral loading onto MSC-based cell carriers (Engineered 5/3 fiber chimerism adenoviruses enter MSCs at a 35-to 3310-fold rate compared to adenovirus 5 wild type capsid.)	[59]
Bone marrow-derived mesenchymal stem cells	Human	Osteocalcin promoter-directed Ad-hOC-E1 oncolytic adenovirus	Renal Cell Carcinoma	Injection of pharmaceutical inducible MSC carrying oncolytic adenovirus combined with vitamin D3 treatment induced effective viral delivery to RCC tumors and significant tumor regression. These were significantly greater than those of injection of carrier-free Ad-hOC-E1.	[60]
Bone marrow-derived mesenchymal stem cells	Human	Adenovirus carrying the IFN-β gene	Glioblastoma	MSCs home to tumors in murine models. MSCs loaded with therapeutic virus injected intra-arterially prolonged median survival of animals.	[61]
Bone marrow-derived mesenchymal progenitor cells	Human	Adenovirus Ad5/3	Ovarian	MSCs home to ovarian tumors, allow virus to replicate, and prolong survival in vivo. (Median survival time of 34 days for mice treated with PBS controls, 44 days for the uninfected MPC transplanted controls, but 69 days in the oncolytic virus-infected MPCs group.)	[62]
Bone marrow-derived mesenchymal stem cells	Human	Adenovirus Delta24-RGD	Glioblastoma	Carotid injections of MSCs loaded with therapeutic eradicated tumors, halted tumor growth, and prolonged survival. (Increase in median survival from 42 days to 75.5 days in murine in vivo models with autotrophic patient derived glioma.)	[63]
Mesenchymal stem cells derived from ovarian cancer patients (ovMSC)	Human	Measles	Ovarian	Migration of ovMSCs to tumors was comparable to that of MSCs derived from healthy donors. Delivery of virus in vivo using mice passively immune to measles yielded similar results upon treatment with MSCs and ovMSCs, both of which elicited longer survival than naked measles virus injection alone. (Median survival for PBS control is 36 days, 37 days for MV injection, but 82 days for MSC/MV injection.)	[64]
Bone marrow-derived mesenchymal stem cells	Human	Measles	Hepatocellular Carcinoma	Systemically delivered MSCs homed to HCC tumors implanted in the liver. MSCs effectively transferred MVs via heterofusion. The therapy inhibited tumor growth in passively immunized SCID mice, which did not occur upon naked MV injections.	[34]
Immortalized fetal brain-derived neural stem cells	Human	Adenoviral vector CRAd-S-pk7	Glioblastoma Multiforme	Viral loaded NSC therapy, when delivered prior to, rather than after conventional therapy prompts 30% longer survival in mice with autotrophic patient-derived glioma compared to application after therapy. (Adenoviral loaded NSC injections in conjunction with XRT-TMZ treatments increased median murine survival 46% compared to XRT-TMZ alone.)	[65]
Immortalized neural stem cell type HB1.F3-CD derived from fetal brain	Human	Adenoviral vector CRAd-S-pk7	Glioblastoma Multiforme	Virus delivered via NSC carrier was localized within the injected hemisphere. NSC carrier cells handed off the therapeutic virus to tumors within 5 days post-injection in vivo in mice with autotrophic patient-derived glioma.	[66]
Human fetal brain-derived neural Stem Cells	Human	Adenovirus	Glioblastoma Multiforme	NSCs are superior viral cell carriers to MSCs in targeting glioma. NSCs release virus at an amount a log higher than MSCs (p < 0.001). NSCs injected intracranially in an orthotropic glioma model increased the survival of tumor bearing animals more robustly than MSCs (median survival for NSCs 68.5 days against 44 days for MSCs, p < 0.002)	[31]