Targeted inhibition of osteosarcoma tumor growth by bone marrow-derived mesenchymal stem cells expressing cytosine deaminase/5-fluorocytosine in tumor-bearing mice

2015 ◽  
Vol 17 (3-5) ◽  
pp. 87-99 ◽  
Author(s):  
Quynh-Anh NguyenThai ◽  
Neelesh Sharma ◽  
Do Huynh Luong ◽  
Simrinder Singh Sodhi ◽  
Jeong-Hyun Kim ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Tumor Growth ◽  
Cytosine Deaminase ◽  
Tumor Bearing ◽  
Targeted Inhibition

Exosomes derived from human bone marrow mesenchymal stem cells promote tumor growth in vivo

2012 ◽  
Vol 315 (1) ◽  
pp. 28-37 ◽  
Author(s):  
Wei Zhu ◽  
Ling Huang ◽  
Yahong Li ◽  
Xu Zhang ◽  
Jianmei Gu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Tumor Growth ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Promote Tumor Growth ◽  
Marrow Mesenchymal Stem Cells

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.

Bone Marrow Mesenchymal Stem Cells (BMSCs) Induces Resistance to Papillary Thyroid Cancer by Activating Janus Kinase/Signal Transducer and Activator of Transcription 3(JAK/STAT3)

2021 ◽  
Vol 11 (9) ◽  
pp. 1805-1811
Author(s):  
Yuanjing Li ◽  
Xing Wen ◽  
Chunfang Peng ◽  
Jiangyan Chen ◽  
Xiang Chen
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Thyroid Cancer ◽  
Tumor Growth ◽  
Papillary Thyroid Cancer ◽  
Cell Invasion ◽  
Akt Pathway ◽  
Papillary Thyroid ◽  
Marrow Mesenchymal Stem Cells

We aimed to explore the mechanism underlying bone marrow mesenchymal stem cells (BMSCs) interacting the drug resistance in papillary thyroid cancer (PTC). In this study, we cultivated and screened cisplatin-resistant PTC cells. The shRNA targeting STAT3 was cloned into the pLKO.1-TRC vector and the vector was transfected into the cancer cells. Afterwards, MTT, Transwell and flow cytometry assay were performed to detect the cell invasion, metastasis and apoptosis, while the expression of JAK pathway related proteins was analyzed through Western blot. Besides, MSCs obtained from mouse blood were co-cultured with treated cells. The cells were injected into mice to detect in vivo effect of STAT3 and BMSCs on tumor growth. Compared with intravenous injection of MSCs, subcutaneous injection more effectively induced resistance to cisplatin, oxaliplatin or carboplatin. Combined treatment of sh-STAT3 restored the sensitivity of tumor cells to chemotherapy. BMSCs injection reduced apoptosis of PTC cells, but hardly affected proliferation. Co-cultivation with BMSCs activated the PI3 K/Akt pathway in PTC cells and enhanced tumor growth. Transfection of shSTAT3 inactivated PI3 K/Akt pathway, promoted cell apoptosis and inhibit cell invasion. Co-culture with BMSCs promotes the malignant invasion of PTC cells through the activation of JAK/STAT3 and induces chemotherapy resistance of PTC cells.

Microvesicles Derived from Human Bone Marrow Mesenchymal Stem Cells Inhibit Tumor Growth

2013 ◽  
Vol 22 (5) ◽  
pp. 758-771 ◽  
Author(s):  
Stefania Bruno ◽  
Federica Collino ◽  
Maria Chiara Deregibus ◽  
Cristina Grange ◽  
Ciro Tetta ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Tumor Growth ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Inhibit Tumor Growth ◽  
Marrow Mesenchymal Stem Cells

scholarly journals Mesenchymal Stem Cells Derived Myofibroblasts Function as Niche Cells in the Normal Bone Marrow and Expand During Carcinogenesis to Promote Tumor Growth

2011 ◽  
Vol 140 (5) ◽  
pp. S-825-S-826
Author(s):  
Michael Quante ◽  
Shuiping Tu ◽  
Hiroyuki Tomita ◽  
Tamas A. Gonda ◽  
Wataru Shibata ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Tumor Growth ◽  
Normal Bone Marrow ◽  
Normal Bone ◽  
Promote Tumor Growth
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