Therapeutic Effects of Genetically Modified Wharton’s Jelly Mesenchymal Stem Cells Expressing Erythropoietin on Breast Cancer-related Anemia in Mice Model

Abstract

Cancer-related anemia (CRA) negatively influences cancer patients’ survival, disease progression, treatment efficacy, and quality of life. Therefore, development of long-lasting and curative therapies is highly required. In this study, we developed cell and gene therapy strategy for in-vivo delivery of EPO cDNA via genetic engineering human Wharton’s jelly mesenchymal stem cells (hWJMSCs) to long-term produce human EPO protein after transplantation into the mice model of CRA. To evaluate CRA's treatment in cancer-free and cancerous conditions, we designed recombinant breast cancer cell line 4T1 expressing herpes simplex virus type 1 thymidine kinase (HSV1-TK) by a lentiviral vector encoding HSV1-TK and injected into mice. After confirming CRA in mice by blood analysis, half of them received ganciclovir for 10 days to clear cancer cells. Meanwhile, we designed another lentiviral vector encoding EPO to transduce hWJMSCs. Following implantation of rhWJMSCs-EPO, the whole peripheral blood samples were collected once per week for 10 weeks. The blood analyzing showed that plasma EPO, hemoglobin (Hb), and hematocrit (Hct) concentration significantly increased and remained at a therapeutic level for >10 weeks in the both treatment groups which indicate that the rhWJMSCs-EPO could improve CRA in both cancer-free and cancerous mice model.