Bone Marrow Derived Mesenchymal Stem Cells (BMSC) from Myeloma Patients Support the Growth of Myeloma Stem Cells
M Perez, Y Feng, J Wen, DS Choi, Y Zu, C-C Chang. The Methodist Hospital and The Methodist Hospital Research Institute, Houston, TX; Tongji Medical College in Huangzhong University of Science and Technology, Wuhan, Hubei, China; Weill Medical College of Cornell University, New York, NY
Background: Myeloma stem cells possess stem cells characteristics, high drug efflux capacity and intracellular drug detoxification activity making them resistant to chemotherapeutic agents. It is well established that normal hematopoitic stem cells reside in specific niches that maintain stem cell quiescence, self-renewal and homeostasis. The interaction between BMSCs and myeloma stem cells has not been well studied, although it is well documented that BMSCs plays essential roles in supporting the growth of mature myeloma cells.
Design: BMSCs from myeloma patients and age-matched controls were obtained and cultured to establish BMSC lines. Dye efflux of Hoechest33342 was used to identify myeloma stem cells based on the “side-population” characteristics generated by their high drug efflux capacity in the myeloma cell line and myeloma patient samples. SP cell populations were co-cultured on BMSCs from normal controls and myeloma patients to access their colony forming ability. To investigate chemotherapeutic resistance, arsenic trioxide and Botezomib were utilized to treat myeloma stem cells co-cultured with BMSC from myeloma patients or controls and then analyzed by flow cytometry for apoptosis. Phenotypic analysis by flow cytometry was also performed to investigate the phenotypic profile of the SP cells and BMSCs. Finally, an animal model was used to assess in vivo growth potential in mice coinjected with BMSCs from myeloma or controls and analyzed by bioluminescent imaging.
Results: Isolation and culture of BMSCs revealed a higher growth potential in myeloma derived BMSCs. Myeloma BMSCs were found to support the growth of myeloma stem cells better than BMSCs from normal controls by forming more colonies. Additionally, myeloma BMSCs appear to enhance the chemoresistance and change the phenotype of myeloma stem cells. Finally, the animal studies show that the mice coinjected with myeloma stem cells and myeloma BMSCs formed larger tumor masses than the mice coinjected with myeloma stem cells and BMSCs from controls.
Conclusions: Our findings suggest that development of novel methods to restore the normal functional status of the BMSC niche in myeloma patients is essential for the long-term cure of myeloma.
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 213, Tuesday Morning