Efficient Generation of Megakaryocyte Progenitors and Platelets From HSPCs via JAK2/STAT3 Signaling
Abstract The supply of platelets for clinical transfusion is often insufficient to meet growing demand. Platelet regeneration from stem cells offers a potential solution to reduce reliance on donor‐based transfusions. However, the current differentiation efficiency is suboptimal. A novel approach is...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-06-01
|
| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202500612 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | Abstract The supply of platelets for clinical transfusion is often insufficient to meet growing demand. Platelet regeneration from stem cells offers a potential solution to reduce reliance on donor‐based transfusions. However, the current differentiation efficiency is suboptimal. A novel approach is presented that significantly enhances platelet yield from hematopoietic stem and progenitor cells (HSPCs) by increasing the production of megakaryocyte progenitors (MkPs) and mature megakaryocytes (MKs). This method employs the overexpression of HES7 combined with the HDAC inhibitor and GABA agonist (collectively termed the VGM cocktail). The VGM cocktail induces MkP production with an efficiency of up to 90%, validated across HSPCs from various donors. These MkPs exhibit extended proliferative capacity, remaining viable for up to 51 days in prolonged culture, and show enhanced maturation into MKs. This differentiation system effectively replicates in vivo thrombocytopoiesis, as evidenced by polyploidization, long protrusions, and proplatelet formation. Transfusion of VGM‐induced MkPs into thrombocytopenic mice results in the release of platelets into circulation. Mechanistic investigation identifies the JAK2/STAT3 signaling pathway as critical in promoting megakaryopoiesis within this system. Therefore, this study demonstrates that the VGM cocktail facilitates enhanced platelet production by promoting MkP generation, offering a promising strategy for in vitro platelet regeneration for clinical applications. |
|---|---|
| ISSN: | 2198-3844 |