Forward programming of hPSCs to neutrophils using chemically defined media
Hayley E Hall1, Xiaoping Bao2, Cheng Dong3,4
1Department of Biomedical Engineering, The Pennsylvania State University, Pennsylvania, USA.
Stem Cell Research & Therapy
|February 2, 2025
Summary
Researchers optimized methods to generate functional neutrophils (PMNs) from human stem cells. This advance is crucial for understanding and treating diseases involving these vital immune cells.
Area of Science:
- Immunology
- Stem Cell Biology
- Hematopoiesis
Background:
- Polymorphonuclear neutrophils (PMNs) are key innate immune cells with short lifespans, necessitating continuous bone marrow production.
- PMNs are increasingly implicated in diseases like sepsis, cancer, and autoimmune disorders, highlighting the need for reliable production methods.
Purpose of the Study:
- To evaluate and optimize protocols for generating functional PMNs from human pluripotent stem cells (hPSCs).
- To compare the efficiency, transcriptomic profiles, and functional maturity of PMNs produced via different differentiation strategies.
Main Methods:
- Three forward programming and one directed differentiation protocol were assessed for PMN generation from hPSCs.
- Differentiation efficiency, transcriptomic profiles, and functional assays were used to characterize the resulting PMNs.
Main Results:
- Both forward programming and directed differentiation successfully generated functional PMNs.
- Optimization of forward programming culture media significantly improved hematopoietic differentiation and neutrophil functional maturity.
Conclusions:
- Forward programming, particularly with optimized media, offers a robust method for generating functional neutrophils from hPSCs.
- This research provides a foundation for developing improved strategies for PMN production for research and therapeutic applications.
Keywords:
Directed DifferentiationETV2Forward programmingHuman pluripotent stem cellsPolymorphonuclear neutrophils
