Neural progenitor cell lines inhibit rat tumor growth in vivo.
Current therapies for gliomas often fail to address their infiltrative nature. Conventional treatments leave behind small clusters of neoplastic cells, resulting in eventual tumor recurrence. In the present study, we have evaluated the antitumor activity of neural progenitor cells against gliomas when stereotactically injected into nucleus Caudatus of Fisher rats. We show that the rat neural progenitor cell lines HiB5 and ST14A, from embryonic hippocampus and striatum primordium, respectively, are able to prolong animal survival and, in 25% of the cases, completely inhibit the outgrowth of N29 glioma compared with control animals. Delayed tumor outgrowth was also seen when HiB5 cells were inoculated at the site of tumor growth 1 week after tumor inoculation or when a mixture of tumor cells and HiB5 cells were injected s.c. into Fisher rats. HiB5 cells were additionally coinoculated together with two alternative rat gliomas, N32 and N25. N32 was growth inhibited, but rats inoculated with N25 cells did not show a prolonged survival. To evaluate the possibility of the involvement of the immune system in the tumor outgrowth inhibition, we show that HiB5 cells do not evoke an immune response when injected into Fisher rats. Furthermore, the rat neural progenitor cells produce all transforming growth factor beta isotypes, which could explain the observed immunosuppressive nature of these cells. Hence, some neural progenitor cells have the ability to inhibit tumor outgrowth when implanted into rats. These results indicate the usefulness of neural stem cells as therapeutically effective cells for the treatment of intracranial tumors.
Department of Cell and Molecular Biology, Section for Tumor Biology, Lund University BMC: I 12, S-221 84 Lund, Sweden. karin.staflin@tumor.lu.se
Karin
K
Staflin
Gabriella
G
Honeth
Suzanne
S
Kalliomäki
Christian
C
Kjellman
Klaus
K
Edvardsen
Magnus
M
Lindvall
D000818:Animals; D001932:Brain Neoplasms / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D003110:Colonic Neoplasms / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D003342:Corpus Striatum / Q000473:pathology; D005910:Glioma / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000166:cytology / Q000502:physiology* / Q000637:transplantation; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D015996:Survival Rate; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014407:Tumor Cells, Cultured
D007166:Immunosuppressive Agents; D016212:Transforming Growth Factor beta