Establishment of Patient-Derived Xenograft (PDX) Zebrafish Model of Multiple Myeloma and Its Application in Drug Screening

Objective: To confirm the in vivo anti-myeloma activity of I3MO (Indirubin-3' -monoxime) in primary patient samples, a patient-derived xenograft (PDX) zebrafish model of MM was utilized. Methods: zebrafish embryos were obtained by the natural spawning of Tubingen strain and incubated at 28°C in embryo medium. The purified CD138+ MM cells fluorescently labeled with Calcein-AM or Dil were injected into the perivitelline space of each embryo of zebrafish at 48 hpf. Engrafted embryos were transferred into 24-well plates and incubated at 28°C in freshly prepared E3 medium containing DMSO, BTZ, I3MO. At 24 hours post injection (hpi), engrafted embryos were detected by fluorescent microscopy to qualify the positive areas with calcein (green) or Dil (red). Results:1. The zebrafish PDX model of MM was successfully applied in the drug effects evaluation. 2. The results in vivo demonstrated that BTZ or I3MO eliminates the engraftment and growth of MM cells in zebrafish embryos (p<0.05). Conclusion: The zebrafish is an ideal model to investigate the cytotoxicity in vivo of compounds on primary MM patient samples.