Mesenchymal stem cells: A new platform for targeting suicide genes in cancer

2017 ◽  
Vol 233 (5) ◽  
pp. 3831-3845 ◽  
Author(s):  
Rana Moradian Tehrani ◽  
Javad Verdi ◽  
Mahdi Noureddini ◽  
Rasoul Salehi ◽  
Reza Salarinia ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Suicide Genes

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.

Proliferation and multi-differentiation potentials of human mesenchymal stem cells on thermoresponsive PDMS surfaces grafted with PNIPAAm

2010 ◽  
Vol 30 (6) ◽  
pp. 455-455 ◽  
Author(s):  
Dongyan Shi ◽  
Dan Ma ◽  
Feiqing Dong ◽  
Chen Zong ◽  
Liyue Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Human Mesenchymal Stem Cells

1417: Mesenchymal Stem Cells Alone or Modified with ENOS Restore Erectile Function in the Aged Rat: Cell-Based Gene Therapy for Erectile Dysfunction

2004 ◽  
Vol 171 (4S) ◽  
pp. 373-373
Author(s):  
Trinity J. Bivalacqua ◽  
Mustafa F. Usta ◽  
Hunter C. Champion ◽  
Weiwen Deng ◽  
Philip J. Kadowitz ◽  
...  
Keyword(s):  
Stem Cells ◽  
Gene Therapy ◽  
Mesenchymal Stem Cells ◽  
Erectile Dysfunction ◽  
Erectile Function ◽  
Aged Rat

Placenta mesenchymal stem cells on a chorion scaffold as a potential osteogenic graft for peripartal bone regeneration

2008 ◽  
Vol 68 (S 01) ◽  
Author(s):  
S Mohr ◽  
BC Portmann-Lanz ◽  
A Schoeberlein ◽  
R Sager ◽  
DV Surbek
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Regeneration

Placenta-derived mesenchymal stem cells for allogenic cardiac cell therapy

2012 ◽  
Vol 60 (S 01) ◽  
Author(s):  
R Roy ◽  
M Kukucka ◽  
D Messroghli ◽  
A Brodarac ◽  
M Becher ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Therapy ◽  
Cardiac Cell ◽  
Cardiac Cell Therapy

The Effect of Link N on the Differentiation of Human Mesenchymal Stem Cells

2012 ◽  
Vol 2 (1_suppl) ◽  
pp. s-0032-1320001-s-0032-1320001
Author(s):  
F. Mwale ◽  
H. T. Wang ◽  
L. Haglund ◽  
P. J. Roughley ◽  
J. Antoniou
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Human Mesenchymal Stem Cells
Sign in / Sign up

Export Citation Format

Share Document