Dr. Maruyama’s research has primarily been focused on calvarial development and diseases. He is particularly interested in cranial sutures, which are small gaps between calvarial bones and filled with mesenchymal cells. These sutures are a growth center for calvaria. Premature fusion of the suture results in craniosynostosis—one of the most frequent causes of skull deformity. Dr. Maruyama’s work has shown that the synostosis could be associated with increased intracranial pressure, difficulties with vision, hearing, and breathing. The only effective treatment is surgical reconstruction of the fused suture. This surgery is extremely difficult due to the close proximity to the brain. Furthermore, in most cases, the affected children need to undergo several rounds of surgeries leading into adulthood. Therefore, it is crucial to understand the underlying mechanism of calvarial development in order to develop efficient strategies for diagnoses, prevention, and treatment of craniosynostosis.
Dr. Maruyama’s research has strongly indicated the essential role of skeletal stem cells during calvarial development and maintenance. However, the existence of stem cells within the suture was just a hypothesis that had never been proven. Dr. Maruyama decided to identify and characterize endogenous skeletal stem cells. He first discovered that the expression of Axin2 is tightly restricted to the midline of suture mesenchyme, a putative stem cell niche. Next, he examined if the Axin2-expressing (Axin2+) cells can meet the rigorous criteria of adult stem cells. Adult stem cells are defined as a cell type that can self-renew for an extended of period of time and differentiate into at least one mature cell type. A lineage-tracing model of Axin2+ cells showed the maintenance of the Axin2-lineage cells for a year, indicating their self-renewing ability. Axin2+ lineage cells also expanded and detected in osteoblast and osteocyte, showing their differentiation ability to mature cell types. Upon injury, these naïve stem cells react drastically and contribute directly to bone repair by replacing the damaged tissue. Animal studies also demonstrated that the bone healing process is facilitated with the transplantation of these stem cells. This impressive finding was published in the high-impact journal Nature Communications in 2016. Dr. Maruyama’s analysis showed that Axin2+ cells in suture mesenchyme are adult stem cells contributing to calvarial development, maintenance, and regeneration. He also demonstrated that the isolated skeletal stem cells possess abilities to engraft, differentiate into skeletogenic cell types, generate bones and enhance repair processes. With this study, Dr. Maruyama was honored at ORS annual convention as the recipient of 2016 Harold M. Frost Young Investigator Award.