Intracellular Delivery of Bone Nanoparticles to Mitigate Irradiation-Induced Damage in Bone Marrow Mesenchymal Stem Cells

This study evaluated the therapeutic potential of intracellularly delivered bone-derived nanoparticles (BPs) in mitigating Ionizing radiation (IR)-induced BMSCs damage. We found that IR exposure caused significant BMSCs dysfunction, including reduced proliferation, increased apoptosis, persistent DNA damage, and a shift toward adipogenic differentiation. Treatment with BPs led to efficient intracellular uptake, improved cell morphology, enhanced proliferation, reduced apoptosis, and preservation of balanced differentiation capacity. Transcriptomic analysis via RNA sequencing revealed that BPs restored key molecular pathways disrupted by IR, particularly those involved in cell cycle regulation, extracellular matrix (ECM) remodeling, and apoptosis. By reversing these transcriptional impairments, BPs supported genomic stability and the regenerative function of BMSCs. Overall design: The third passage BMSCs were seeded at a density of 1 × 105 cells per well in 12-well plates and divided into three experimental groups: Control group: BMSCs without IR exposure or BP co-culture. IR group: BMSCs exposed to IR treatment. IR&BP group: BMSCs exposed to IR followed by BP co-culture.After 7 days of culture, total RNA was extracted from all groups (n=3 per group) using the RNeasy Plus Mini Kit (Qiagen) following the manufacturer's instructions. RNA concentration was measured using the Nanodrop ND-1000, and quality was assessed via capillary electrophoresis (Agilent Technologies). RNA sequencing (RNA-Seq) was performed by Novogene Corporation Inc.