Ultrasound-Mediated Mesenchymal Stem Cells Transfection as a Targeted Cancer Therapy Platform.
Mesenchymal stem cells (MSCs) hold tremendous potential as a targeted cell-based delivery platform for inflammatory and cancer therapy. Genetic manipulation of MSCs, however, is challenging, and therefore, most studies using MSCs as therapeutic cell carriers have utilized viral vectors to transduce the cells. Here, we demonstrate, for the first time, an alternative approach for the efficient transfection of MSCs; therapeutic ultrasound (TUS). Using TUS with low intensities and moderate frequencies, MSCs were transfected with a pDNA encoding for PEX, a protein that inhibits tumor angiogenesis, and studied as a cell vehicle for in vivo tumor therapy. TUS application did not alter the MSCs' stemness or their homing capabilities, and the transfected MSCs transcribed biologically active PEX. Additionally, in a mouse model, 70% inhibition of prostate tumor growth was achieved following a single I.V. administration of MSCs that were TUS-transfected with pPEX. Further, the repeated I.V. administration of TUS-pPEX transfected-MSCs enhanced tumor inhibition up to 84%. Altogether, these results provide a proof of concept that TUS-transfected MSCs can be effectively used as a cell-based delivery approach for the prospective treatment of cancer.
Faculty of Biotechnology &Food Engineering, Technion - Israel Institute of Technology, Haifa, 32000, Israel.
Tom
T
Haber
Faculty of Biotechnology &Food Engineering, Technion - Israel Institute of Technology, Haifa, 32000, Israel.
Limor
L
Baruch
Faculty of Biotechnology &Food Engineering, Technion - Israel Institute of Technology, Haifa, 32000, Israel.
Marcelle
M
Machluf
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D015870:Gene Expression; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D058990:Molecular Targeted Therapy / Q000379:methods*; D053402:PHEX Phosphate Regulating Neutral Endopeptidase / Q000235:genetics* / Q000378:metabolism; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D051381:Rats; D013010:Sonication / Q000379:methods; D014162:Transfection / Q000295:instrumentation / Q000379:methods*; D019076:Transgenes; D014183:Transplantation, Heterologous; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
D017077:Culture Media, Conditioned; D053402:PHEX Phosphate Regulating Neutral Endopeptidase; C506231:PHEX protein, human