Cell Res：钱鹏旭/黄河/姜洪源合作证实，瞬时机械激活Piezo1，促进体外造血干细胞扩增

Core Viewpoint - The article discusses the challenges in the clinical application of hematopoietic stem cells (HSCs) due to insufficient sources, low in vitro expansion efficiency, and loss of function, highlighting the importance of mechanical signals in HSC expansion and the innovative approach using Piezo1 channel activation for effective HSC growth [3][4][6]. Group 1: Research Findings - A study published in Cell Research reveals the dual regulatory role of the Piezo1 channel in HSC ex vivo expansion, emphasizing that it is essential but should not be over-activated [4]. - The research team identified that Piezo1 is highly expressed in HSCs, and its auxiliary subunit Mdfic/Mdfi is co-expressed in long-term HSCs (LT-HSCs) [6]. - Polymer microspheres of 500 nm diameter and moderate stiffness (PS500) were found to optimize HSC expansion in co-culture systems [6][7]. Group 2: Mechanism of Action - PS500 activates the Piezo1 channel through a mechanism involving size matching, dynamic contact, and mechanical transduction, inducing local membrane deformation and generating pN-level forces [7]. - The PS500 microspheres exhibit higher Brownian motion speed and directional interaction frequency with HSCs compared to larger microspheres, facilitating multiple light touches rather than continuous pressure [7]. Group 3: Functional Outcomes - HSCs expanded using PS500 maintained robust hematopoietic reconstitution ability in continuous transplantation experiments, with long-term survival of recipient mice [9]. - Human umbilical cord blood HSCs expanded with PS500 demonstrated efficient implantation and multi-lineage reconstitution in immunodeficient mice [9]. - The study established a scalable expansion system based on oscillatory culture, confirming the clinical applicability of this strategy [9]. Group 4: Clinical Implications - The research introduces a novel non-invasive mechanical intervention strategy for HSC expansion, offering advantages over traditional biochemical methods, including non-invasiveness, non-heritable changes, and scalability [9]. - This work addresses the clinical supply challenges of HSC transplantation and suggests potential applications of mechanical-sensitive channel interventions in other hard-to-expand stem cell types and immune cell function modulation, which could lead to breakthroughs in tumor immunotherapy, tissue engineering, and organ regeneration [9].