Healing of bone defects by induced pluripotent stem cell-derived bone marrow mesenchymal stem cells seeded on hydroxyapatite-zirconia

Abstract

Background

Induced pluripotent stem cells (iPSCs) can generate bone marrow mesenchymal stem cells (BMSCs) as seed cells for tissue-engineered bone to repair bone defects. In this study, we investigated the effects of hydroxyapatite-zirconia (HA/ZrO₂) composites combined with iPSC-derived BMSCs as a bone substitute on repairing skull defects in rats.

Methods

Human urinary cells isolated from a healthy donor were reprogramed into iPSCs and then induced into BMSCs. Immunocytochemistry (IHC) and reverse transcription-polymerase chain reaction (RT-PCR) were used to examine the characteristics of the induced MSCs. The iPSC-derived BMSCs were cultured on HA/ZrO₂ composites, and cytocompatibility of the composite was analyzed by cell counting kit-8 (CCK-8) assays, RT-PCR, and scanning electron microscopy. Then, HA/ZrO₂ combined with iPSC-derived expanded potential stem cells (EpSCs) were transplanted onto skull defects of rats. The effects of this composite on bone repair were evaluated by IHC.

Results

The results showed that MSCs induced from iPSCs displayed the phenotypes and property of normal BMSCs. After seeding on the HA/ZrO₂, iPSC-derived BMSCs had the ability to proliferate and differentiate into osteoblasts. After transplantation, iPSC-derived BMSCs on HA/ZrO₂ promoted construction of bone on rat skulls.

Conclusions

These results indicated that transplantation of a HA/ZrO₂ combined with iPS-derived BMSCs is feasible to reconstruct bones and may be a substantial reference for iPSC-based therapy for bone defects.

Keywords: Induced pluripotent stem cell (iPSC), bone marrow mesenchymal stem cells (BMSCs), bone regeneration, hydroxyapatite-zirconia (HA/ZrO₂)