Human adipose tissue-derived mesenchymal stromal cells as vehicles for tumor bystander effect: a model based on bioluminescence imaging.
Human adipose tissue mesenchymal stromal cells (AMSCs) share common traits, including similar differentiation potential and cell surface markers, with their bone marrow counterparts. Owing to their general availability, higher abundance and ease of isolation AMSCs may be convenient autologous delivery vehicles for localized tumor therapy. We demonstrate a model for tumor therapy development based on the use of AMSCs expressing renilla luciferase and thymidine kinase, as cellular vehicles for ganciclovir-mediated bystander killing of firefly luciferase expressing tumors, and noninvasive bioluminescence imaging to continuously monitor both, tumor cells and AMSCs. We show that the therapy delivering AMSCs survive long time within tumors, optimize the ratio of AMSCs to tumor cells for therapy, and asses the therapeutic effect in real time. Treatment of mice bearing prostate tumors plus therapeutic AMSCs with the prodrug ganciclovir induced bystander killing effect, reducing the number of tumor cells to 1.5 % that of control tumors. Thus, AMSCs could be useful vehicles to deliver localized therapy, with potential for clinical application in inoperable tumors and surgical borders after tumor resection. This approach, useful to evaluate efficiency of therapeutic models, should facilitate the selection of cell types, dosages, therapeutic agents and treatment protocols for cell-based therapies of specific tumors.
Vilalta
M
M
Cardiovascular Research Center (CSIC-ICCC), CIBER-BBN, Barcelona, Spain.
Dégano
I R
IR
Bagó
J
J
Aguilar
E
E
Gambhir
S S
SS
Rubio
N
N
Blanco
J
J
D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D024201:Bystander Effect; D002454:Cell Differentiation; D049109:Cell Proliferation; D015774:Ganciclovir / Q000008:administration & dosage; D041722:Genes, Transgenic, Suicide; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D008163:Luminescent Measurements; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011471:Prostatic Neoplasms / Q000473:pathology / Q000628:therapy*; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D015774:Ganciclovir