In Vivo Study for Clinical Application of Dental Stem Cell Therapy Incorporated with Dental Titanium Implants.

Hyunmin Choi,Seung-Han Oh,Hong-Seok Moon,June-Sung Shim,Narae Jung,Hyung-Jun Kim,Seung-Yup Ku,Kyu-Hyung Park,Young-Bum Park,Yoon Young Kim

doi:10.3390/ma14020381

Abstract

The aim of this study was to investigate the behavior of dental-derived human mesenchymal stem cells (d-hMSCs) in response to differently surface-treated implants and to evaluate the effect of d-hMSCs on local osteogenesis around an implant in vivo. d-hMSCs derived from alveolar bone were established and cultured on machined, sandblasted and acid-etched (SLA)-treated titanium discs with and without osteogenic induction medium. Their morphological and osteogenic potential was assessed by scanning electron microscopy (SEM) and real-time polymerase chain reaction (RT-PCR) via mixing of 5 × 106 of d-hMSCs with 1 mL of Metrigel and 20 μL of gel-cell mixture, which was dispensed into the defect followed by the placement of customized mini-implants (machined, SLA-treated implants) in New Zealand white rabbits. Following healing periods of 2 weeks and 12 weeks, the obtained samples in each group were analyzed radiographically, histomorphometrically and immunohistochemically. The quantitative change in osteogenic differentiation of d-hMSCs was identified according to the type of surface treatment. Radiographic analysis revealed that an increase in new bone formation was statistically significant in the d-hMSCs group. Histomorphometric analysis was in accordance with radiographic analysis, showing the significantly increased new bone formation in the d-hMSCs group regardless of time of sacrifice. Human nuclei A was identified near the area where d-hMSCs were implanted but the level of expression was found to be decreased as time passed. Within the limitations of the present study, in this animal model, the transplantation of d-hMSCs enhanced the new bone formation around an implant and the survival and function of the stem cells was experimentally proven up to 12 weeks post-sacrifice.

Highlights

The establishment of osseointegration is one of the key factors for the long-term success of oral implants and many previous studies have reported that osseointegration can be manipulated and improved by changing implant surface properties [1,2,3,4,5,6,7,8]
Several investigators have evaluated the effect of implant surface treatment on osteogenic differentiation of human mesenchymal stem cells (hMSCs) in vitro [15,16,17,18], there has been less extensive in vivo literature on the fate of hMSCs on differently surface treated implants for clinical application
It can be anticipated that greater knowledge regarding the fate of hMSCs on implant surfaces, especially hMSCs obtained from dental origin, could lead to greater clinical implant success and further understanding of the underlying mechanisms governing the fate of derived human mesenchymal stem cells (d-hMSCs)

Summary

Introduction

The establishment of osseointegration is one of the key factors for the long-term success of oral implants and many previous studies have reported that osseointegration can be manipulated and improved by changing implant surface properties [1,2,3,4,5,6,7,8]. Several investigators have evaluated the effect of implant surface treatment on osteogenic differentiation of hMSCs in vitro [15,16,17,18], there has been less extensive in vivo literature on the fate of hMSCs on differently surface treated implants for clinical application. It can be anticipated that greater knowledge regarding the fate of hMSCs on implant surfaces, especially hMSCs obtained from dental origin, could lead to greater clinical implant success and further understanding of the underlying mechanisms governing the fate of d-hMSCs. the aim of this study was to investigate the behavior of d-hMSCs in response to differently surface-treated implants and to evaluate the effect of d-hMSCs on local osteogenesis around an implant in vivo

Objectives

Methods

Results

Conclusion