PUBLICATION
FDA-Approved Drug Screening for Compounds That Facilitate Hematopoietic Stem and Progenitor Cells (HSPCs) Expansion in Zebrafish
- Authors
- Feng, Z., Lin, C., Tu, L., Su, M., Song, C., Liu, S., Suryanto, M.E., Hsiao, C.D., Li, L.
- ID
- ZDB-PUB-210828-28
- Date
- 2021
- Source
- Cells 10(8): (Journal)
- Registered Authors
- Hsiao, Chung-Der, Li, Li
- Keywords
- HSPCs expansion, drug screening, vitamins, zebrafish
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Apoptosis/drug effects*
- Apoptosis/genetics
- Calcifediol/pharmacology
- Calcitriol/pharmacology
- Cell Proliferation/drug effects*
- Cell Proliferation/genetics
- Cholecalciferol/pharmacology
- Drug Approval*
- Drug Evaluation, Preclinical/methods
- Gene Expression/drug effects
- Hematopoietic Stem Cells/cytology*
- Humans
- In Situ Hybridization/methods
- Larva/cytology
- Larva/drug effects
- Larva/metabolism
- Pharmaceutical Preparations/administration & dosage*
- Pharmaceutical Preparations/classification
- Vitamins/pharmacology
- Zebrafish
- PubMed
- 34440919 Full text @ Cells
Citation
Feng, Z., Lin, C., Tu, L., Su, M., Song, C., Liu, S., Suryanto, M.E., Hsiao, C.D., Li, L. (2021) FDA-Approved Drug Screening for Compounds That Facilitate Hematopoietic Stem and Progenitor Cells (HSPCs) Expansion in Zebrafish. Cells. 10(8):.
Abstract
Hematopoietic stem cells (HSCs) are a specialized subset of cells with self-renewal and multilineage differentiation potency, which are essential for their function in bone marrow or umbilical cord blood transplantation to treat blood disorders. Expanding the hematopoietic stem and progenitor cells (HSPCs) ex vivo is essential to understand the HSPCs-based therapies potency. Here, we established a screening system in zebrafish by adopting an FDA-approved drug library to identify candidates that could facilitate HSPC expansion. To date, we have screened 171 drugs of 7 categories, including antibacterial, antineoplastic, glucocorticoid, NSAIDS, vitamins, antidepressant, and antipsychotic drugs. We found 21 drugs that contributed to HSPCs expansion, 32 drugs' administration caused HSPCs diminishment and 118 drugs' treatment elicited no effect on HSPCs amplification. Among these drugs, we further investigated the vitamin drugs ergocalciferol and panthenol, taking advantage of their acceptability, limited side-effects, and easy delivery. These two drugs, in particular, efficiently expanded the HSPCs pool in a dose-dependent manner. Their application even mitigated the compromised hematopoiesis in an ikzf1-/- mutant. Taken together, our study implied that the larval zebrafish is a suitable model for drug repurposing of effective molecules (especially those already approved for clinical use) that can facilitate HSPCs expansion.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping