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A Functional Bioluminescent Zebrafish Screen for Enhancing Hematopoietic Cell Homing
Yuliana Astuti1, Ashley C Kramer1, Amanda L Blake1
1Department of Pediatrics, Blood and Marrow Transplant Program, University of Minnesota Medical School, MMC 366, 420 Delaware Street Southeast, Minneapolis, MN 55455, USA.
Stem Cell Reports
|January 3, 2017
Summary
Researchers discovered ergosterol, a natural compound, enhances hematopoietic stem cell homing and engraftment. This finding, observed in zebrafish and mice, utilized bioluminescence imaging for efficient screening of small molecules.
Area of Science:
- * Hematology
- * Molecular Biology
- * Pharmacology
Background:
- * Hematopoietic cell homing is crucial for successful adoptive transfer and engraftment.
- * Current methods for monitoring cell homing are often invasive or lack sensitivity.
- * Developing efficient screening systems is essential for identifying novel homing modulators.
Purpose of the Study:
- * To establish a zebrafish model for screening small molecules that enhance hematopoietic cell homing.
- * To identify novel compounds that improve hematopoietic stem cell engraftment after adoptive transfer.
- * To validate the utility of in vivo bioluminescence imaging for monitoring cell homing.
Main Methods:
- * Creation of a transgenic zebrafish model (ubi:luc) for bioluminescence imaging (BLI) of hematopoietic cells.
- * Utilization of BLI to track donor cell homing to the bone marrow post-transplantation.
- * Functional screening of small molecules to identify enhancers of hematopoietic cell homing.
- * In vitro assessment of ergosterol's effects on cell expansion and CXCR4 expression.
Main Results:
- * Bioluminescence imaging successfully detected hematopoietic cell homing as early as one day post-transplant.
- * Prostaglandin E2 demonstrated a detectable biological effect on early homing and engraftment.
- * Ergosterol, a phytosterol, was identified as a compound that enhances hematopoietic cell homing in both zebrafish and mice.
- * Ergosterol treatment increased CXCR4 expression and promoted the expansion of specific stem cell populations (Lin-SCA-1+KIT+) in vitro.
Conclusions:
- * In vivo BLI in adult zebrafish provides a non-invasive method to monitor donor hematopoietic cell activity.
- * This zebrafish model serves as an effective functional screen for identifying mediators of cellular homing.
- * Ergosterol shows potential as a therapeutic agent to improve hematopoietic stem cell engraftment.

