scholarly journals Preclinical analysis of human mesenchymal stem cells: tumor tropism and therapeutic efficiency of local HSV-TK suicide gene therapy in glioblastoma

Oncotarget ◽  
2019 ◽  
Vol 10 (58) ◽  
pp. 6049-6061 ◽  
Author(s):  
Lasse Dührsen ◽  
Sophie Hartfuß ◽  
Daniela Hirsch ◽  
Sabine Geiger ◽  
Cecile L. Maire ◽  
...  
Keyword(s):  
Stem Cells ◽  
Gene Therapy ◽  
Mesenchymal Stem Cells ◽  
Human Mesenchymal Stem Cells ◽  
Suicide Gene ◽  
Suicide Gene Therapy ◽  
Therapeutic Efficiency ◽  
Tumor Tropism

scholarly journals 366. Suicide Gene Therapy of Glioma Using Genetically Engineered Human Mesenchymal Stem Cells

2006 ◽  
Vol 13 ◽  
pp. S139
Author(s):  
Hiroki Namba ◽  
Shaoyi Li ◽  
Tsutomu Tokuyama ◽  
Junkoh Yamamoto ◽  
Naoki Yokota
Keyword(s):  
Stem Cells ◽  
Gene Therapy ◽  
Mesenchymal Stem Cells ◽  
Human Mesenchymal Stem Cells ◽  
Suicide Gene ◽  
Genetically Engineered ◽  
Suicide Gene Therapy

Mesenchymal Stem Cells as Suicide Gene Therapy Vehicles for Organ-Confined and Metastatic Prostate Cancer (PCa).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5148-5148
Author(s):  
Rosetta Martiniello-Wilks ◽  
Stephen R. Larsen ◽  
Stephane Flamant ◽  
Jessamy C. Tiffen ◽  
Charles G. Bailey ◽  
...  
Keyword(s):  
Stem Cells ◽  
Gene Therapy ◽  
Mesenchymal Stem Cells ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Suicide Gene ◽  
Suicide Gene Therapy ◽  
Prostate Tumors ◽  
Suicide Genes ◽  
Tumor Bearing

Abstract The efficacy of mesenchymal stem cells (MSC) is currently being examined as a clinical regenerative medicine for multiple sclerosis, cirrhosis, liver disease, tibial fractures, heart failure and graft versus host disease. MSC display an inherent tumor-tropic property that has been exploited for the targeted delivery of therapeutic genes to metastatic melanoma, glioma, breast and colon carcinoma in animal models. Advantages of using MSC include their ability for: self-renewal, ease of propagation and gene modification ex vivo; secretion of high levels of therapeutic protein; evasion of immune rejection; differentiation into connective tissue and tumor stroma; and long-term engraftment in vivo. This study explores the utility of MSC to deliver reporter or suicide genes to advanced Pca which is currently incurable using the syngeneic RM1 mouse model. Sca-1bright CD45− cells sorted from adherent bone marrow cells were shown to be true MSC by their ability to undergo tri-lineage differentiation in adipogeneic, osteogenic and chondrogenic media and their characteristic CD44+, CD90+, CD73+ and CD106+ phenotype. Lentiviral vectors showed sustained green fluorescent protein (GFP) reporter gene expression in MSC (MSC-GFP) for 50 passages by flow cytometry. When MSC-GFP (10e6 cells) were implanted into the mouse prostate with or without RM1 tumor cells on day 0, examination by full body fluorescence imaging (IVIS 100; Xenogen/Caliper) showed MSC persisted only within the tumor-bearing prostate (p<0.05; day 18). No MSC were detected in any other organ examined. To test their systemic homing ability, MSC-GFP (10e6 cells) were infused every second day (2–14) via the tail vein of mice in the presence or absence of RM1 lung pseudometastases. MSC persisted within the lungs of RM1 tumor-bearing mice alone (p<0.01) with no detectable MSC in any other organ examined (day 18). These results suggest MSC engraft organ-confined Pca and home to metastatic Pca. Gene directed enzyme prodrug therapy (GDEPT) describes the transfer of a suicide gene, not expressed in mammalian cells, into tumors using viral vectors. This renders tumors sensitive to prodrugs that are non-toxic to normal tissues. In our pre-clinical study, prostate tumors established from RM1 tumor cells stably transfected with fusion suicide gene cytosine deaminase/uracil phosphoribosyltransferase (CDUPRT) followed by systemic treatment with prodrug 5-fluorocytosine, showed significant reductions in prostate tumor growth and pseudometastases in the lungs (1). More recently, we stably transfected MSC with CDUPRT prior to implantation into established RM1 prostate tumors. In the presence of prodrug MSC-CDUPRT showed similar levels of Pca killing observed in the published experiment. In both experiments CDUPRT in the presence of prodrug significantly reduced (∼75%; p<0.05) the weight of RM1 prostate tumors compared to the control gene or no prodrug control mice. These results demonstrate that MSC can deliver suicide genes to developing Pca and efficiently convert prodrug to a toxic diffusible metabolite to suppress tumor growth. MSC implantation was well tolerated without observed toxicity and therefore show promise as a novel form of cell-directed suicide gene therapy.

Engineered mesenchymal stem cells as vectors in a suicide gene therapy against preclinical murine models for solid tumors

2016 ◽  
Vol 239 ◽  
pp. 82-91 ◽  
Author(s):  
Ikrame Amara ◽  
Elodie Pramil ◽  
Catherine Senamaud-Beaufort ◽  
Audrey Devillers ◽  
Rodney Macedo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Gene Therapy ◽  
Mesenchymal Stem Cells ◽  
Solid Tumors ◽  
Suicide Gene ◽  
Suicide Gene Therapy ◽  
Murine Models

Tumoricidal bystander effect in the suicide gene therapy using mesenchymal stem cells does not injure normal brain tissues

2011 ◽  
Vol 306 (1) ◽  
pp. 99-105 ◽  
Author(s):  
Shinji Amano ◽  
Chunyu Gu ◽  
Shinichiro Koizumi ◽  
Tsutomu Tokuyama ◽  
Hiroki Namba
Keyword(s):  
Stem Cells ◽  
Gene Therapy ◽  
Mesenchymal Stem Cells ◽  
Bystander Effect ◽  
Suicide Gene ◽  
Suicide Gene Therapy ◽  
Normal Brain ◽  
Brain Tissues

Human Mesenchymal Stem Cells Lack Tumor Tropism but Enhance the Antitumor Activity of Oncolytic Adenoviruses in Orthotopic Lung and Breast Tumors

2007 ◽  
Vol 18 (7) ◽  
pp. 627-641 ◽  
Author(s):  
Tanja Hakkarainen ◽  
Merja Särkioja ◽  
Petri Lehenkari ◽  
Susanna Miettinen ◽  
Timo Ylikomi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Antitumor Activity ◽  
Human Mesenchymal Stem Cells ◽  
Breast Tumors ◽  
Oncolytic Adenoviruses ◽  
Tumor Tropism

Gene therapy based on human mesenchymal stem cells: Strategies and methods

2010 ◽  
Vol 44 (1) ◽  
pp. 61-65 ◽  
Author(s):  
A. V. Shakhbazau ◽  
S. M. Kosmacheva ◽  
N. A. Kartel’ ◽  
M. P. Potapnev
Keyword(s):  
Stem Cells ◽  
Gene Therapy ◽  
Mesenchymal Stem Cells ◽  
Human Mesenchymal Stem Cells

scholarly journals Adipose Tissue–Derived Human Mesenchymal Stem Cells Mediated Prodrug Cancer Gene Therapy

2007 ◽  
Vol 67 (13) ◽  
pp. 6304-6313 ◽  
Author(s):  
Lucia Kucerova ◽  
Veronika Altanerova ◽  
Miroslava Matuskova ◽  
Silvia Tyciakova ◽  
Cestmir Altaner
Keyword(s):  
Stem Cells ◽  
Gene Therapy ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Human Mesenchymal Stem Cells ◽  
Cancer Gene Therapy ◽  
Cancer Gene
Sign in / Sign up

Export Citation Format

Share Document