| First Author | Zhang X | Year | 2023 |
| Journal | Cell Stem Cell | Volume | 30 |
| Issue | 4 | Pages | 378-395.e8 |
| PubMed ID | 37028404 | Mgi Jnum | J:350830 |
| Mgi Id | MGI:7463862 | Doi | 10.1016/j.stem.2023.03.005 |
| Citation | Zhang X, et al. (2023) Harnessing matrix stiffness to engineer a bone marrow niche for hematopoietic stem cell rejuvenation. Cell Stem Cell 30(4):378-395.e8 |
| abstractText | Hematopoietic stem cell (HSC) self-renewal and aging are tightly regulated by paracrine factors from the bone marrow niche. However, whether HSC rejuvenation could be achieved by engineering a bone marrow niche ex vivo remains unknown. Here, we show that matrix stiffness fine-tunes HSC niche factor expression by bone marrow stromal cells (BMSCs). Increased stiffness activates Yap/Taz signaling to promote BMSC expansion upon 2D culture, which is largely reversed by 3D culture in soft gelatin methacrylate hydrogels. Notably, 3D co-culture with BMSCs promotes HSC maintenance and lymphopoiesis, reverses aging hallmarks of HSCs, and restores their long-term multilineage reconstitution capacity. In situ atomic force microscopy analysis reveals that mouse bone marrow stiffens with age, which correlates with a compromised HSC niche. Taken together, this study highlights the biomechanical regulation of the HSC niche by BMSCs, which could be harnessed to engineer a soft bone marrow niche for HSC rejuvenation. |
