FDA-Approved Drug Screening for Compounds That Facilitate Hematopoietic Stem and Progenitor Cells (HSPCs) Expansion in Zebrafish
Zhi Feng,
Chenyu Lin,
Limei Tu,
Ming Su,
Chunyu Song,
Shengnan Liu,
Michael Edbert Suryanto,
Chung-Der Hsiao,
Li Li
Affiliations
Zhi Feng
Key Laboratory of Freshwater Fish Reproduction and Development, Institute of Developmental Biology and Regenerative Medicine, Ministry of Education, Southwest University, Chongqing 400715, China
Chenyu Lin
Key Laboratory of Freshwater Fish Reproduction and Development, Institute of Developmental Biology and Regenerative Medicine, Ministry of Education, Southwest University, Chongqing 400715, China
Limei Tu
Key Laboratory of Freshwater Fish Reproduction and Development, Institute of Developmental Biology and Regenerative Medicine, Ministry of Education, Southwest University, Chongqing 400715, China
Ming Su
Key Laboratory of Freshwater Fish Reproduction and Development, Institute of Developmental Biology and Regenerative Medicine, Ministry of Education, Southwest University, Chongqing 400715, China
Chunyu Song
Key Laboratory of Freshwater Fish Reproduction and Development, Institute of Developmental Biology and Regenerative Medicine, Ministry of Education, Southwest University, Chongqing 400715, China
Shengnan Liu
Key Laboratory of Freshwater Fish Reproduction and Development, Institute of Developmental Biology and Regenerative Medicine, Ministry of Education, Southwest University, Chongqing 400715, China
Michael Edbert Suryanto
Department of Bioscience Technology, Chung Yuan Christian University, Taoyuan 320314, Taiwan
Chung-Der Hsiao
Department of Bioscience Technology, Chung Yuan Christian University, Taoyuan 320314, Taiwan
Li Li
Research Center of Stem Cells and Ageing, Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing 400714, China
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.
