RNA-Sequencing Reveals Unique Features of Multipotent Mesenchymal Stromal Cells from Oral and Maxillofacial Tissue Transcriptomes

Background: Multipotent mesenchymal stromal cells (MSCs) can be isolated from numerous tissues and are attractive candidates for therapeutic clinical applications due to their immunomodulatory and pro-regenerative capacity. Although the minimum criteria for defining MSCs have been defined, their characteristics are known to vary depending on their tissue of origin. Methods: We isolated and characterized human MSCs from three different bones (ilium (I-MSCs), maxilla (Mx-MSCs) and mandibular (Md-MSCs)) and proceeded with next generation RNA-sequencing. Furthermore, to investigate the gene expression profiles among other cell types, we obtained RNA-seq data of numerous types of MSCs from the Sequence Reads Archive and analyze the transcriptome profile. Findings: We analyzed RNA-sequencing data of several MSC types and found that those from tissues of the maxillofacial region, such as the jaw bone and periodontal ligament, were HOX-negative, while those from other tissues were HOX-positive. We also identified the genes strongly expressed in maxillofacial tissue-derived MSCs were involved in the craniofacial development. Interpretation: Our findings suggest that MSCs from different anatomical locations, despite meeting general characterization criteria, have remarkable differences in gene expression and positional memory. Although stromal cells from different anatomical sources are generally categorized as MSCs, their differentiation potential and biological functions vary. We suggested that MSCs may retain a memory of the developmental process, including gene expression profiles. This could have important impact when choosing appropriate cell source for regenerative therapy using MSCs. Funding: This study was supported by the Japan Agency for Medical Research and Development and the Japan Society for the Promotion of Science. Declaration of Interest: No authors have potential conflicts of interest, including financial interests or relationships or affiliations, relevant to the subject of this manuscript. Ethical Approval: This study was approved by the Ethics Committee at Tokyo Women’s Medical University and Kitasato University that examines the use of tissues of human cell origin, and was conducted after the acquisition of written informed consent from patients or their families.