Stromal cell-derived factor-1α-encapsulated albumin/heparin nanoparticles for induced stem cell migration and intervertebral disc regeneration in vivo
Stromal cell-derived factor-1α-encapsulated albumin/heparin nanoparticles for induced stem cell migration and intervertebral disc regeneration in vivo
复制标题
基质细胞衍生因子 1 α 封装的白蛋白/肝素纳米颗粒用于诱导干细胞迁移和体内椎间盘再生
DOI：
10.1016/j.actbio.2018.03.032
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发表时间：
2018-05-01
影响因子：
9.7
通讯作者：
Gao，Changyou
中科院分区：
文献类型：
--
作者：
Zhang，Hua;Yu，Shan;Gao，Changyou
椎间盘退变可引起多种疾病和疼痛。干细胞向IVD变性部位的迁移是IVD再生的关键因素。在目前的研究中，我们制备了白蛋白/肝素纳米颗粒（BHNPs）作为基质细胞衍生因子-1α （SDF-1α，也称为C-X-C基序趋化因子12）的可注射载体，SDF-1α是一种强大的化学吸引剂，用于骨髓间充质干细胞（MSCs）的归巢，以保护分子免受降解并持续释放。NPs具有相对均匀的小尺寸，直径约为110 nm。NPs具有较高的SDF-1α负载能力，并具有缓释特性。然后在体外和体内研究获得的BHNPs/SDF的生物活性。BHNPs/SDF可诱导MSCs在体外以剂量依赖的方式迁移。BHNPs/SDF注入受损椎间盘后，与单独使用SDF-1α和BHNPs相比，BHNPs/SDF诱导纤维环和髓核的再生效果更好，组织学分级评分更高，SOX9、Aggrecan和II型胶原在mRNA和蛋白水平上的表达也更高。该研究提供了一个简单的纳米平台来加载SDF-1α并保护其免受降解，在体内诱导组织再生中具有潜在的应用前景。干细胞向IVD变性部位的迁移是促进IVD再生的关键事件。在本研究中，我们制备了白蛋白/肝素纳米颗粒（BHNPs）作为可注射载体，以保护SDF-1α免受降解并促进分子的持续释放。与单独使用SDF-1α和BHNPs相比，将BHNPs/SDF注射到受损椎间盘后，可诱导更好的IVD再生。该研究提供了一个简单的纳米平台来加载SDF-1α并保护其免受降解，在体内诱导组织再生中具有潜在的应用前景。
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.Statement of significanceStem 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.