Chromosomal instability in human mesenchymal stem cells immortalized with human papilloma virus E6, E7, and hTERT genes

Takeuchi, Masao; Takeuchi, Kikuko; Kohara, Arihiro; Satoh, Masaharu; Shioda, Shigeo; Ozawa, Yutaka; Ohtani, Azusa; Morita, Keiko; Hirano, Takashi; Terai, Masanori; Umezawa, Akihiro; Mizusawa, Hiroshi

doi:10.1007/s11626-007-9057-x

Cited by 3 publications

(3 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…With respect to the first mechanism, several genes have been evaluated for their potential utility in immortalizing stem cells for use as delivery vehicles: the proto-oncogene v-myc, 3,70,72,[89][90][91] the catalytic component of the telomerase complex (human telomerase reverse transcriptase (hTERT)), human papillomavirus type 16 E6/E7 genes, Bmi-1 [92][93][94][95][96][97][98][99] and an N-terminal fragment of SV40 large T-antigen. 2,100 Characteristics of the resultant cell lines, each of which had extended life spans in culture, have been reviewed.…”

Section: Toxicity/tumorigenicitymentioning

confidence: 99%

Stem and progenitor cell-mediated tumor selective gene therapy

2008

View full text Add to dashboard Cite

The poor prognosis for patients with aggressive or metastatic tumors and the toxic side effects of currently available treatments necessitate the development of more effective tumor-selective therapies. Stem/progenitor cells display inherent tumor-tropic properties that can be exploited for targeted delivery of anticancer genes to invasive and metastatic tumors. Therapeutic genes that have been inserted into stem cells and delivered to tumors with high selectivity include prodrug-activating enzymes (cytosine deaminase, carboxylesterase, thymidine kinase), interleukins (IL-2, IL-4, IL-12, IL-23), interferon-b, apoptosis-promoting genes (tumor necrosis factor-related apoptosis-inducing ligand) and metalloproteinases (PEX). We and others have demonstrated that neural and mesenchymal stem cells can deliver therapeutic genes to elicit a significant antitumor response in animal models of intracranial glioma, medulloblastoma, melanoma brain metastasis, disseminated neuroblastoma and breast cancer lung metastasis. Most studies reported reduction in tumor volume (up to 90%) and increased survival of tumor-bearing animals. Complete cures have also been achieved (90% disease-free survival for 41 year of mice bearing disseminated neuroblastoma tumors). As we learn more about the biology of stem cells and the molecular mechanisms that mediate their tumor-tropism and we identify efficacious gene products for specific tumor types, the clinical utility of cell-based delivery strategies becomes increasingly evident.

show abstract

Section: Toxicity/tumorigenicitymentioning

confidence: 99%

Stem and progenitor cell-mediated tumor selective gene therapy

2008

View full text Add to dashboard Cite

show abstract

“…Therefore the incorporation of immortalizing genes has been explored as an approach to maintain cell lines indefinitely [1]. Immortalizing transgenes include the proto-oncogene v- myc [101,105–110], human telomerase reverse transcriptase (hTERT) [111–118], human papillomavirus type 16 E6/E7 [119–122], Bmi-1 [123–129], and the N-terminal fragment of SV40 large T-antigen [1,130–133]. Notably, the potential tumorigenic capacity of these immortalized cells lines is not well-studied, and it is unknown whether loss of normal cell-cycle checkpoint controls, karyotypic instability, or other undesired changes may occur after transfection [1,134].…”

Section: Malignant Transformation From Incorporation Of Transgenesmentioning

confidence: 99%

The Oncogenic Potential of Mesenchymal Stem Cells in the Treatment of Cancer: Directions for Future Research

Momin¹,

Vela²,

Zaidi³

et al. 2010

CIR

View full text Add to dashboard Cite

Mesenchymal stem cells (MSCs) represent a promising new approach to the treatment of several diseases that are associated with dismal outcomes. These include myocardial damage, graft versus host disease, and possibly cancer. Although the potential therapeutic aspects of MSCs continue to be well-researched, the possible hazards of MSCs, and in particular their oncogenic capacity are poorly understood. This review addresses the oncogenic and tumor-supporting potential of MSCs within the context of cancer treatment. The risk for malignant transformation is discussed for each stage of the clinical lifecycle of MSCs. This includes malignant transformation in vitro during production phases, during insertion of potentially therapeutic transgenes, and finally in vivo via interactions with tumor stroma. The immunosuppressive qualities of MSCs, which may facilitate evasion of the immune system by a tumor, are also addressed. Limitations of the methods employed in clinical trials to date are reviewed, including the absence of long term follow-up and lack of adequate screening methods to detect formation of new tumors. Through discussions of the possible oncogenic and tumor-supporting mechanisms of MSCs, directions for future research are identified which may eventually facilitate the future clinical translation of MSCs for the treatment of cancer and other diseases.

show abstract

“…cells was prolonged by infecting them with a retrovirus containing human papillomavirus E7 and telomerase reverse transcriptase (hTERT) cDNAs (Mori et al, 2005;Shimomura et al, 2007;Ishii et al, 2008;Takeuchi et al, 2007). We first tested the ability of hESF9 medium, which we had developed for use with hES cells, to support the growth of UE7T-13 cells.…”

mentioning

confidence: 99%

Growth factor-defined culture medium for human mesenchymal stem cells

Mimura¹,

Kimura²,

Hirata³

et al. 2011

Int. J. Dev. Biol.

Self Cite

View full text Add to dashboard Cite

Human bone marrow-derived mesenchymal stem cells (hMSCs) are potential cellular sources of therapeutic stem cells as they have the ability to proliferate and differentiate into a wide array of mesenchymal cell types such as osteoblasts, chondroblasts and adipocytes. hMSCs have been used clinically to treat patients with graft vs. host disease, osteogenesis imperfect, or alveolar cleft, suggesting that transplantation of hMSCs is comparatively safe as a stem cell-based therapy. However, conventional culture medium for hMSCs contains fetal bovine serum (FBS). In the present study, we developed a growth factor-defined, serum-free medium for culturing hMSCs. Under these conditions, TGF-    1 promoted proliferation of hMSCs. The expanded hMSC population expressed the human pluripotency markers SSEA-3, -4, NANOG, OCT3/4 and SOX2. Furthermore, double positive cells for SSEA-3 and a mesenchymal cell marker, CD105, were detected in the population. The potential to differentiate into osteoblasts and adipocytes was confirmed. This work provides a useful tool to understand the basic biological properties of hMSCs in culture.

show abstract

Chromosomal instability in human mesenchymal stem cells immortalized with human papilloma virus E6, E7, and hTERT genes

Cited by 3 publications

References 0 publications

Stem and progenitor cell-mediated tumor selective gene therapy

Stem and progenitor cell-mediated tumor selective gene therapy

The Oncogenic Potential of Mesenchymal Stem Cells in the Treatment of Cancer: Directions for Future Research

Growth factor-defined culture medium for human mesenchymal stem cells

Contact Info

Product

Resources

About