Osteoporosis-Improving Effects of Extracellular Vesicles from Human Amniotic Membrane Stem Cells in Ovariectomized Rats

Osteoporosis is a common skeletal disease characterized by decreased bone density, leading to bone fragility and bone fractures, especially in menopausal women. Mesenchymal stem cells have a potential to differentiate into osteocytes, so directly reconstruct bone tissue or facilitate bone regeneration via paracrine effects. It is known that paracrine effects are mediated by functional molecules delivered in extracellular vesicles (EVs) released from stem cells. EVs containing high concentrations of growth factors (GFs) and neurotrophic factors (NFs) were attained via hypoxia culture of human amnotic membrane mesenchymal stem cells (AMSCs). Sprague-Dawley rats were ovariectomized, and 8 weeks later, intravenously injected with EVs at doses of 1 x 108, 3 x 108 or 1 x 109 particles/100 μL/body weekly for 8 weeks. One week after the final administration, the serum and bone parameters related to bone density were analyzed. Serum 17β-estradiol, alkaline phosphatase, and calcium levels decreased in ovariectomized rats were restored by EVs in a dose-dependent manner. Bone parameters such as bone mineral density, bone mineral content, bone volume/tissue volume ratio, trabecular number, trabecular space, and bending strength were also improved by treatment with EVs. Such effects were confirmed by morphological findings of micro-computed tomography. Taken together, it is suggested that AMSC-EVs containing high concentrations of GFs and NFs preserve bone soundness by promoting bone regeneration and inhibiting bone resorption.