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

Acta Biomater. 2018 May:72:217-227. doi: 10.1016/j.actbio.2018.03.032. Epub 2018 Mar 26.

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.

Statement of significance: 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.

Keywords: C-X-C motif chemokine 12; Intervertebral disc; Nanoparticles; Stem cell migration; Stromal cell-derived factor-1α.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albumins* / chemistry
  • Albumins* / pharmacokinetics
  • Albumins* / pharmacology
  • Animals
  • Cell Movement / drug effects*
  • Chemokine CXCL12* / chemistry
  • Chemokine CXCL12* / pharmacokinetics
  • Chemokine CXCL12* / pharmacology
  • Heparin* / chemistry
  • Heparin* / pharmacokinetics
  • Heparin* / pharmacology
  • Intervertebral Disc* / injuries
  • Intervertebral Disc* / physiology
  • Male
  • Mesenchymal Stem Cells / metabolism*
  • Nanoparticles* / chemistry
  • Nanoparticles* / therapeutic use
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Wistar
  • Regeneration / drug effects*

Substances

  • Albumins
  • CXCL12 protein, rat
  • Chemokine CXCL12
  • Heparin