Retracted: Tumor Tropism of Intravenously Injected Human‐Induced Pluripotent Stem Cell‐Derived Neural Stem Cells and Their Gene Therapy Application in a Metastatic Breast Cancer Model

Abstract

Human pluripotent stem cells can serve as an accessible and reliable source for the generation of functional human cells for medical therapies. In this study, we used a conventional lentiviral transduction method to derive humaninduced pluripotent stem (iPS) cells from primary human fibroblasts and then generated neural stem cells (NSCs) from the iPS cells. Using a dual-color whole-body imaging technology, we demonstrated that after tail vein injection, these human NSCs displayed a robust migratory capacity outside the central nervous system in both immunodeficient and immunocompetent mice and homed in on established orthotopic 4T1 mouse mammary tumors. To investigate whether the iPS cell-derived NSCs can be used as a cellular delivery vehicle for cancer gene therapy, the cells were transduced with a baculoviral vector containing the herpes simplex virus thymidine kinase suicide gene and injected through tail vein into 4T1 tumor-bearing mice. The transduced NSCs were effective in inhibiting the growth of the orthotopic 4T1 breast tumor and the metastatic spread of the cancer cells in the presence of ganciclovir, leading to prolonged survival of the tumorbearing mice. The use of iPS cell-derived NSCs for cancer gene therapy bypasses the sensitive ethical issue surrounding the use of cells derived from human fetal tissues or human embryonic stem cells. This approach may also help to overcome problems associated with allogeneic transplantation of other types of human NSCs. STEM CELLS

Antitumor Effects of CD40 Ligand-Expressing Endothelial Progenitor Cells Derived From Human Induced Pluripotent Stem Cells in a Metastatic Breast Cancer Model

“…Other types of adult stem cells, such as mesenchymal stem cells (MSCs) and neural stem cells (NSCs), as well as MSCs and NSCs derived from pluripotent stem cells, also show the ability to home to tumors [17,[32][33][34][35]. However, it has been noted that MSCs that reach tumor stroma can contribute to tumor development through the mechanisms of creating a niche to support cancer stem cells, promoting angiogenesis, and/or promoting cancer metastasis [36][37][38].…”

“…Human iPS cells were generated using a polycistronic lentiviral vector encoding the Oct4, Klf4, Sox2, and c-Myc genes (Millipore, Bedford, MA, http://www.millipore.com), as stated in our previous study [17]. iPS cells were cultured on Matrigel (BD Biosciences, San Jose, CA, http://www.bdbiosciences.com) using mTeSR medium (StemCell Technologies, Vancouver, BC, Canada, http://www.stemcell.com).…”

Development of Anti-Cancer Stem Cells as Theranostic Agents in the Treatment of Different Cancer Types: An Update

“…Furthermore, neural SCs not only consolidate into the primary tumor surroundings and also move in the direction of the intracranial micro-satellite that characterizes malignant tumors of brain e.g., glioblastoma [134]. A various types of human SCs have tumor-tropic characteristics [137][138][139]. In tumor-tropism of SCs cellular and molecular procedures are complicated.…”

Frontiers in Suicide Gene Therapy of Cancer

“…The stem cells are being tested for their potential for carrying the suicidal genes also into variety of other tumors [135][136][137][138][139][140][141][142][143][144][145][146][147][148].…”

“…HSV-TK is effectively used in cancer suicide gene therapy by expression in targeted cells to exert intracellular effects outlined above [15][16][17][18][19][22][23][24]. Alternatively, TK is also secreted into the extracellular fluids by genetically engineered cells [135][136][137][138][139][140][141][142][143][144][145][146][147][148]. Thereafter, it is internalized by surrounding cancer cells to cause their death.…”