A Novel Therapeutic Strategy for Bone Marrow Failure: Niche Rejuvenation Using Costal Cartilage-Derived Stem Cells.

Abstract

The bone marrow (BM) niche plays a critical role in maintaining hematopoietic stem cell function but is highly vulnerable to damage from chemotherapy and radiation. However, current therapeutic strategies for BM niche failure remain significantly limited. The previous study demonstrate that costal cartilage-derived stem cells (CDSCs) exhibit substantial self-renewal and bone-forming capacity; however, whether and how CDSCs contribute to BM microenvironment maintenance remains unknown. In this study, the co-transplantation of CDSCs with multipotent progenitors (MPPs) successfully rescued lethally irradiated mice. By contrast, transplantation of mesenchymal stem cells with MPPs or MPPs alone fails to rescue the mice, suggesting a potential role of CDSCs in hematopoietic reconstitution. RNA-seq and experimental data suggest that CDSCs are involved in rejuvenating the BM niche. Mechanistically, CDSCs not only differentiate into niche components, including bone marrow stromal cells, endothelial cells, and osteoblasts, but also secrete pro-hematopoietic cytokines, thereby rejuvenating the irradiated microenvironment. Additionally, CDSCs protect residual hematopoietic stem and progenitor cells from radiation-induced apoptosis and DNA damage while enhancing niche repair. Finally, through synergy with cyclosporine A, CDSCs markedly enhance hematopoietic recovery in mice with aplastic anemia. Collectively, these findings establish CDSCs as a versatile platform for treating BM failure via microenvironmental restoration.