Stromal cell-derived factor-1α-encapsulated albumin/heparin nanoparticles for induced stem cell migration and intervertebral disc regeneration in vivo.

Abstract

Intervertebral disc (IVD) degeneration may cause many diseases and pain. Stem cell migration toward the site of IVD degeneration is a key factor for IVD regeneration. In the current study, we prepared albumin/heparin nanoparticles (BHNPs) as injectable carriers of stromal cell-derived factor-1α (SDF-1α, also known as C-X-C motif chemokine 12), a powerful chemoattractant for the homing of bone marrow resident mesenchymal stem cells (MSCs), for protection of the molecule against degradation for a sustained release. The NPs have relatively uniform small size, with a diameter of about 110 nm. The NPs possess a high loading capacity of SDF-1α with a sustained release profile. The bioactivity of the obtained BHNPs/SDF was then studied in vitro and in vivo. The BHNPs/SDF can induce migration of MSCs in a dose-dependent manner in vitro. After injected into the damaged disc, BHNPs/SDF induce much better regeneration of annulus fibrosus and nucleus pulposus, compared to SDF-1α and BHNPs alone, evidenced with better histological grade scores and higher expression of SOX9, Aggrecan, and Collagen type II at the level of both mRNA and protein. This study provides a simple nanoplatform to load SDF-1α and protect it against degradation, with potential application in inductive tissue regeneration in vivo. Stem cell migration toward the site of IVD degeneration is a key event to promote IVD regeneration. In the current study, we prepared albumin/heparin nanoparticles (BHNPs) as injectable carriers to protect SDF-1α against degradation and for the sustained release of the molecule. After injected into the damaged disc, BHNPs/SDF induced much better regeneration of IVD, compared to SDF-1α and BHNPs alone. This study provides a simple nanoplatform to load SDF-1α and protect it from degradation, with potential application in inductive tissue regeneration in vivo.