Exosomes from Mesenchymal Stem Cells for Treatment of Malignant Mesothelioma
Abstract
Over the past decade, trafficking of extracellular vesicles including exosomes has emerged as a mechanism of cell-cell communication and plays an important role in tumorigenesis and formation of tumor microenvironment. We hypothesize that different antitumor activities of CD90low and CD90high mesenchymal stem cells (MSCs) are applicable to treatment of malignant mesothelioma (MM) and that the effects of MSCs are related to their secreted exosomes. Exosome-based nanometric vehicles have a number of advantages: they are non-toxic, non-immunogenic, and can be engineered to have robust delivery capacity and targeting specificity. During this study period, we have successfully generated adipose tissue derived mesenchymal stem cells (ADSCs) which were characterized as a typical MSC phenotypes (CD45-CD34-CD31-CD11b-CD29+CD44+CD73+CD90+CD105+CD106+SCA-1+, here briefly called CD90high). The cells were continuously cultured in MSC conditioned media with additional 1 ng/ml of LPS or 100 ng/ml of bacterial heat shock protein 70 (HSP70) and until passages 4 phenotypically differentiated into CD45-CD34-CD31-CD11b-CD29+CD44+CD73+CD90-CD105+CD106+SCA-1+, briefly called CD90low, while cells cultured without LPS or HSP70 maintained CD90high. BothCD90high and CD90 low ADSCs were capable of further differentiating into osteoblasts and adipocytes in specific differentiation induction media. A week after luciferase-labeled mesothelioma cell line 40L (40L-luc) cells were intraperitoneally (i.p.) inoculated into C57BL/6j mice, tumor-bearing mice were treated i.p. with four doses of 1106 of passage-4 CD90low or CD90high ADSCs at 7-day interval. Tumor growth was monitored by in vivo bioluminescent imaging weekly and tumors were collected a week after the last treatment and weighted. Treatment with CD90low ADSC significantly slowed tumor growth and reduced tumor mass compared to treatment with CD90high ADSCs or differentiated fibroblast cells as control.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2021
- Accession Number
- AD1153330
Entities
People
- Huabiao Chen
Organizations
- Massachusetts General Hospital