Tumor-homing effect of human mesenchymal stem cells in a TH-MYCN mouse model of neuroblastoma.
BACKGROUND
Human mesenchymal stem cells (hMSCs) are multipotent stem-like cells that are reported to have tumor-suppression effects and migration ability toward damaged tissues or tumors. The aim of this study was to analyze the tumor-homing ability of hMSCs and antitumor potency in a transgenic TH-MYCN mouse model of neuroblastoma (NB).


METHODS
hMSCs (3×106) labeled with DiR, a lipophilic near-infrared dye, were intraperitoneally (i.p.) or intravenously (i.v.) administered to the TH-MYCN mice. hMSC in vivo kinetics were assayed using the IVIS® imaging system for 24h after injection. Immunohistochemistry using human CD90 antibody was also performed to confirm the location of hMSCs in various organs and tumors. Furthermore, the survival curve of TH-MYCN mice treated with hMSCs was compared to a control group administered PBS.


RESULTS
i.p. hMSCs were recognized in the tumors of TH-MYCN mice by IVIS. hMSCs were also located inside the tumor tissue. Conversely, most of the i.v. hMSCs were captured by the lungs, and migration into the tumors was not noted. There was no significant difference in the survival between the hMSC and control groups.


CONCLUSIONS
The present study suggested that hMSCs may be potential tumor-specific therapeutic delivery vehicles in NB according to their homing potential to tumors.
Department of Pediatric Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Koseki
K
Kimura
Department of Immunology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Tsunao
T
Kishida
Department of Pediatric Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Junko
J
Wakao
Department of Pediatric Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Tomoko
T
Tanaka
Department of Pediatric Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Mayumi
M
Higashi
Department of Pediatric Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Shigehisa
S
Fumino
Department of Pediatric Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Shigeyoshi
S
Aoi
Department of Pediatric Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Taizo
T
Furukawa
Department of Immunology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Osam
O
Mazda
Department of Pediatric Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan. Electronic address: taji@koto.kpu-m.ac.jp.
Tatsuro
T
Tajiri
D000818:Animals; D006801:Humans; D007150:Immunohistochemistry; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental; D009447:Neuroblastoma / Q000473:pathology / Q000601:surgery*; D014407:Tumor Cells, Cultured
Homing; IVIS; Mesenchymal stem cell; Neuroblastoma; TH-MYCN transgenic mouse