LARGE-SCALE GENE EXPRESSION PROFILIING OF MESENCHYMAL STEM CELLS EXPOSED TO SMOOTH TANTALUM VS. TITANIUM SURFACES

Abstract

Metallic implants are widely used in orthopedic, oral and maxillofacial surgery. Durable osseous fixation of an implant requires that osteoprogenitor cells attach and adhere to the implant, proliferate, differentiate into osteoblasts, and produce mineralized matrix. We previously observed that human mesenchymal stem cells (MSCs) adherent to smooth tantalum (Ta) surfaces demonstrated superior biocompatibility compared with titanium (Ti) coatings.

The aim of the present study was to investigate the interactions between MSCs and smooth surfaces of Ta and by means of whole-genome microarray technology.

Immortalized human mesenchymal stem cells were cultivated on smooth surfaces of Ti and Ta. Total RNA was extracted after culturing for 1, 2, 4, and 8 days and hybridized to Affymetrix whole-genome microarrays (N=16). Replicate arrays were averaged and the ratios of gene expression by MSCs cultivated on Ta versus Ti coating were calculated. Absolute fold differences were also calculated and lists of upregulated genes were generated. Moreover, gene Ontology (GO) annotation analysis of differentially regulated genes was performed.

For both Ta and Ti coatings, the vast majority of genes were upregulated after 4 d of cultivation. Genes upregulated by MSCs cultivated on Ta coating for 4 d were annotated to relevant GO terms. Ti-regulated GO annotation clusters were predominantly transcription-related. By using the K-means clustering algorithm, 10 clusters containing more than 5 genes were identified. Moreover, various genes related to osteogenesis and cell adhesion were upregulated by MSCs exposed to Ta surface.

Microarray analysis of MSCs exposed to smooth metallic surfaces of both Ta and Ti generally showed a huge increase in transcriptional activity after 4 d of cultivation. According to GO annotation analysis Ta coating may induce increased adhesion and earlier differentiation of MSCs compared to Ti surface making Ta a promising biocompatible material for bone implants.