Rat umbilical cord stem cells completely abolish rat mammary carcinomas with no evidence of metastasis or recurrence 100 days post-tumor cell inoculation.
Genetically engineered stem cells efficiently deliver therapeutic proteins to cancer and other sites of inflammation. However, a major advantage would be realized if tumor-trafficking stem cells that have not been genetically modified exhibit an inherent antitumor effect, thus circumventing the necessity of the expression of exogenous genes by the cells. We transplanted Fisher 344 rat-derived mammary adenocarcinoma cells (Mat B III) orthotopically into syngeneic F344 rats with an intact immune system. Rat umbilical cord matrix stem (rUCMS) cells derived from Wharton's jelly were then administered intratumoral (i.t) or i.v. 4 days later. The tumor attenuation effect was significantly evident starting from day 14 in i.v. and i.t. rUCMS cell-transplanted rats compared with sham-transplanted rats. In addition, unmodified rUCMS cell-transplanted rats showed complete regression of tumors to undetectable levels by 34 to 38 days with no evidence of metastasis or recurrence 100 days post-tumor cell inoculation. Dye-loaded rUCMS cells were identified within tumors only 4 days after their i.v. transplantation. In vitro colony assays with rUCMS cells as feeder layers markedly reduced Mat B III colony size and number. Growth attenuation of Mat B III cells exposed to either rUCMS cells directly or to the conditioned medium derived from rUCMS cells was associated with apoptosis indicators, including increased activated caspase-3. In addition, rUCMS cells cocultured with Mat B III cells had a dose-dependent antiproliferative effect on Mat B III cells. These findings suggest that unmodified human UCMS cells could be used for targeted cytotherapy for breast cancer.
Ganta
Chanran
C
Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, Kansas 66506, USA. ckganta@vet.k-state.edu
Chiyo
Doi
D
Ayuzawa
Rie
R
Rachakatla
Rajashekar
R
Pyle
Marla
M
Andrews
Gordon
G
Weiss
Mark
M
Tamura
Masaaki
M
Troyer
Deryl
D
D000230:Adenocarcinoma / Q000473:pathology / Q000628:therapy*; D000818:Animals; D036101:Cord Blood Stem Cell Transplantation; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000473:pathology / Q000628:therapy*; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D051381:Rats; D011916:Rats, Inbred F344