Towards Tissue-Specific Stem Cell Therapy for the Intervertebral Disc: PPARδ Agonist Increases the Yield of Human Nucleus Pulposus Progenitor Cells in Expansion
Xingshuo Zhang,
Julien Guerrero,
Andreas S. Croft,
Katharina A.C. Oswald,
Christoph E. Albers,
Sonja Häckel,
Benjamin Gantenbein
Affiliations
Xingshuo Zhang
Tissue Engineering for Orthopaedics & Mechanobiology (TOM), Department for BioMedical Research (DBMR) of the Faculty of Medicine of the University of Bern, University of Bern, CH-3008 Bern, Switzerland
Julien Guerrero
Tissue Engineering for Orthopaedics & Mechanobiology (TOM), Department for BioMedical Research (DBMR) of the Faculty of Medicine of the University of Bern, University of Bern, CH-3008 Bern, Switzerland
Andreas S. Croft
Tissue Engineering for Orthopaedics & Mechanobiology (TOM), Department for BioMedical Research (DBMR) of the Faculty of Medicine of the University of Bern, University of Bern, CH-3008 Bern, Switzerland
Katharina A.C. Oswald
Department of Orthopaedic Surgery and Traumatology, Inselspital, Bern University Hospital, University of Bern, CH-3010 Bern, Switzerland
Christoph E. Albers
Department of Orthopaedic Surgery and Traumatology, Inselspital, Bern University Hospital, University of Bern, CH-3010 Bern, Switzerland
Sonja Häckel
Department of Orthopaedic Surgery and Traumatology, Inselspital, Bern University Hospital, University of Bern, CH-3010 Bern, Switzerland
Benjamin Gantenbein
Tissue Engineering for Orthopaedics & Mechanobiology (TOM), Department for BioMedical Research (DBMR) of the Faculty of Medicine of the University of Bern, University of Bern, CH-3008 Bern, Switzerland
(1) Background: Low back pain (LBP) is often associated with intervertebral disc degeneration (IVDD). Autochthonous progenitor cells isolated from the center, i.e., the nucleus pulposus, of the IVD (so-called nucleus pulposus progenitor cells (NPPCs)) could be a future cell source for therapy. The NPPCs were also identified to be positive for the angiopoietin-1 receptor (Tie2). Similar to hematopoietic stem cells, Tie2 might be involved in peroxisome proliferator-activated receptor delta (PPARδ) agonist-induced self-renewal regulation. The purpose of this study was to investigate whether a PPARδ agonist (GW501516) increases the Tie2+ NPPCs’ yield within the heterogeneous nucleus pulposus cell (NPC) population. (2) Methods: Primary NPCs were treated with 10 µM of GW501516 for eight days. Mitochondrial mass was determined by microscopy, using mitotracker red dye, and the relative gene expression was quantified by qPCR, using extracellular matrix and mitophagy-related genes. (3) The NPC’s group treated with the PPARδ agonist showed a significant increase of the Tie2+ NPCs yield from ~7% in passage 1 to ~50% in passage two, compared to the NPCs vehicle-treated group. Furthermore, no significant differences were found among treatment and control, using qPCR and mitotracker deep red. (4) Conclusion: PPARδ agonist could help to increase the Tie2+ NPCs yield during NPC expansion.
