Human bone scaffolds support clonal persistence and functional retention of MDS-derived CD34+ cells in a 3D in vitro bone marrow model
Abstract
Introduction:
Myelodysplastic neoplasms (MDS) are clonal hematopoietic disorders with ineffective hematopoiesis and risk of progression to acute myeloid leukemia, predominantly affecting elderly patients. Modeling disease-specific interactions for understanding pathogenesis and therapeutic vulnerabilities in MDS remains challenging. The bone marrow (BM) niche is essential for the maintenance and regulation of hematopoietic stem and progenitor cells (HSPCs). In MDS, alterations in this microenvironment drive ineffective hematopoiesis and clonal evolution. Murine xenografts lack human microenvironmental features and raise ethical concerns, while 2D or static co-cultures fail to mimic BM architecture. To address this, we used a perfusion bioreactor and compared synthetic hydroxyapatite scaffolds with decellularized human trabecular bone to establish a humanized 3D BM niche for functional MDS studies. We hypothesized that bone scaffolds better preserve perivascular stromal niches, particularly CD146⁺/Nestin⁺/NG2⁺ pericytes known to regulate HSC quiescence, explaining superior hematopoietic support compared to hydroxyapatite.
Methods:
Decellularized trabecular scaffolds from femoral heads were compared to commercial hydroxyapatite scaffolds. Scaffolds were pre-seeded with mesenchymal stromal cells (MSCs) and stromal vascular fraction for four weeks, then seeded with CD34⁺ BM cells from four MDS patients (MDS-EB2, MDS-EB-1, MDS-MLD, and MDS-EB-2). Samples were obtained with…
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