RESUMEN
One-dimensional hydroxyapatite (HA) particularly mimics the structure of mineralized collagen fibrils and displays superior mechanical properties such as toughness. Herein, we report Se-doped HA/chitosan (Se-HA/CS) biopapers constructed with self-assembled Se-doped HA nanowires and chitosan. The Se-HA/CS biopapers with high flexibility and manufacturability can not only be further processed into arbitrary shapes by folding or using scissors but also display high performances in in vitro/vivo anti-bone tumor studies. The Se-HA/CS biopapers are more inclined to inhibit the growth of tumor cells (HCS 2/8 and SJSA cells) than that of normal human bone marrow stromal cells (hBMSCs). The potential mechanisms of this meaningful anti-tumor effect were investigated, such as reactive oxygen species accumulation and the activation of apoptosis and the underlying signal pathway involved (including caspase family, Bcl-2 family and JNK/STAT3). The results demonstrate that Se-HA/CS biopapers may inhibit the growth of HCS 2/8 and SJSA cells by synchronously inducing JNK activation and STAT3 inhibition and consequently promote the apoptosis of these cells. Furthermore, the in vivo anti-tumor studies confirm that the Se-HA/CS biopapers obviously suppress the growth of patient-derived xenograft tumor models.
Asunto(s)
Antineoplásicos/química , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Neoplasias Óseas/patología , Durapatita/química , Selenio/química , Selenio/farmacología , Animales , Línea Celular Tumoral , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones , Nanocables/química , Papel , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Bone tissue engineering is a promising treatment strategy to increase bone regeneration. Endothelial progenitor cells (EPCs) and bone marrow stromal cells (BMSCs) are commonly used to promote vessel formation and osteoblastic differentiation in tissue engineering. Previous studies have demonstrated that EPCs regulate both proliferation and differentiation of BMSCs. However, the underlying mechanism remains unclear. Understanding this mechanism is critical to developing more effective treatments. The role of extracellular vesicles in celltocell communication has attracted substantial attention. These small vesicles deliver proteins, DNA, and RNA and consequently regulate the commitment, function, and differentiation of target cells. In the present study, EPCderived extracellular vesicles (EPCEVs were isolated using gradient ultracentrifugation and ultrafiltration and the influence of EPCEVs on BMSC osteoblastic differentiation and proliferation was examined in vitro. The results indicated that EPCEVs regulate the osteoblastic differentiation of BMSCs by inhibiting the expression of osteogenic genes and increasing proliferation in vitro. It is suggested that the results regarding the role of EPCEVs will provide a novel way to explain the crosstalk between EPCs and BMSCs.