Rat Umbilical Cord Stem Cells Completely Abolish Rat Mammary Carcinomas with No Evidence of Metastasis or Recurrence 100 Days Post–Tumor Cell Inoculation

Abstract

Genetically engineered stem cells efficiently deliver therapeutic proteins to cancer and other sites of inflammation. However, a major advantage would be realized if tumortrafficking 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 celltransplanted 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.

Induction of apoptosis in glioma cells requires cell-to-cell contact with human umbilical cord blood stem cells

“…In this study, as a necessary preliminary step, they evaluated the effect of unengineered rat umbilical cord blood stem cells on Matt B III cancer cells in vitro and in vivo. To their surprise, the stem cells them-selves mediated a profound anti-tumor effect both in vivo and in vitro (17). In the present study, we demonstrate this anti-tumor effect in vivo and in vitro using human glioma cell lines and xenografts.…”

“…As demonstrated, the authors used the co-culture method to obtain the effector/ target (E/T) cell ratios of 0:1, 1:1, 5:1, and 10:1 (16). A recent report has demonstrated that rat umbilical cord blood stem cells completely abolish rat mammary carcinomas with no evidence of metastasis or recurrence at 100 days post-tumor cell inoculation (17). In this study, as a necessary preliminary step, they evaluated the effect of unengineered rat umbilical cord blood stem cells on Matt B III cancer cells in vitro and in vivo.…”

Wharton's Jelly Stem Cells as Agents for Cancer Therapy

“…The G0/G1 arrest is evident in the decrease of CDK2 expression [50]. In vivo studies showed that both human and rat UCMSC treatment significantly decreased tumor weights [32,33,49,50]. In particular, intratumoral or systemic administration of rat UCMSC caused complete regression of orthotopic Mat B III grafts in the female F344 rat mammary gland to undetectable levels by 34 to 38 days (Fig.…”

The Effect of Wharton's Jelly Mesenchymal Stem Cells on a Squamous Cell Carcinoma Cell Line

“…Further, injection of WJMSCs into immune-deficient mice did not produce teratomas [18]. The versatility and availability of umbilical cord stem cells make them a potent resource for transplant therapies for various diseases, including cancer [20].…”

“…Ganta et al, [20] observed that rats with mammary carcinoma showed complete regression of the lesion with no evidence of metastases following intra-tumoral injection of rat umbilical cord matrix-derived stem cells. Similarly, intravenous injection of unengineered human MSCs in a xenotransplant rat model with induced human breast carcinoma led to a decrease in cancer burden as a result of the human MSCs homing to pulmonary metastases [24].…”