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A Novel Rescue Strategy for Bone Marrow Hematopoietic Failure via Microenvironment Reconstruction with Reduced HSC Dependency

ABSTRACT: Hematopoietic stem cell transplantation (HSCT) represents the most effective therapeutic approach for hematopoietic malignancies, bone marrow (BM) failure syndromes, and primary immunodeficiency diseases. However, the clinical demand for HSCT is constrained by current limitations in HSC sources and expansion technologies. The BM niche is crucial providing a supportive microenvironment for the self-renewal and differentiation of HSCs, and its rejuvenation is essential for rapid and effective hematopoietic recovery. In this study, we demonstrate that costal-cartilage-derived stem cells (CDSCs) can achieve hematopoietic reconstruction comparable to HSCT, even with a significantly reduced number of hematopoietic stem and progenitor cells (HSPCs), while exhibiting low chimerism. We further show that transplanted CDSCs differentiate into various cell types, including bone marrow stromal cells (BMSCs), endothelial cells, and osteoblasts, and secrete pro-hematopoietic factors that restore the damaged BM niche. Moreover, in vitro-expanded CDSCs exhibit elevated expression of BMSC markers and enhance hematopoietic recovery in injury models. Notably, the combination of CDSCs with cyclosporine A is effective in treating aplastic anemia in mouse models. Collectively, these findings propose a novel strategy for treating BM hematopoietic failure through microenvironmental restoration and broaden the potential therapeutic scope of HSCT.

ORGANISM(S): Mus musculus

PROVIDER: GSE289526 | GEO | 2025/02/14

REPOSITORIES: GEO

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A Novel Rescue Strategy for Bone Marrow Hematopoietic Failure via Microenvironment Reconstruction with Reduced HSC Dependency [RNA-Seq]

Project description:Hematopoietic stem cell transplantation (HSCT) represents the most effective therapeutic approach for hematopoietic malignancies, bone marrow (BM) failure syndromes, and primary immunodeficiency diseases. However, the clinical demand for HSCT is constrained by current limitations in HSC sources and expansion technologies. The BM niche is crucial providing a supportive microenvironment for the self-renewal and differentiation of HSCs, and its rejuvenation is essential for rapid and effective hematopoietic recovery. In this study, we demonstrate that costal-cartilage-derived stem cells (CDSCs) can achieve hematopoietic reconstruction comparable to HSCT, even with a significantly reduced number of hematopoietic stem and progenitor cells (HSPCs), while exhibiting low chimerism. We further show that transplanted CDSCs differentiate into various cell types, including bone marrow stromal cells (BMSCs), endothelial cells, and osteoblasts, and secrete pro-hematopoietic factors that restore the damaged BM niche. Moreover, in vitro-expanded CDSCs exhibit elevated expression of BMSC markers and enhance hematopoietic recovery in injury models. Notably, the combination of CDSCs with cyclosporine A is effective in treating aplastic anemia in mouse models. Collectively, these findings propose a novel strategy for treating BM hematopoietic failure through microenvironmental restoration and broaden the potential therapeutic scope of HSCT.

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