The Interplay of Mesenchymal Stem Cells and Neutrophils During Rapid Maxillary Expansion

This K08 proposal outlines a five-year research career development program focused on elucidating the biological role of mesenchymal stem cells (MSCs) and their interaction with neutrophils during mid-palatal suture expansion/distraction osteogenesis. The candidate is an instructor in the Department of Orthodontics at Penn Dental Medicine. Building on previous research and clinical experience in addressing transverse problems in orthodontic treatment, this proposal aims to equip the candidate with multidisciplinary skills essential for transitioning to an independent clinician-scientist with expertise in stem cell biology and osteoimmunology. Clinically, patients with maxillary transverse deficiency (MTD) exhibit varied responses to rapid maxillary expansion (RME), which is often more challenging in opening the mid-palatal suture in skeletally mature patients. While new techniques such as TAD-supported or surgical- assisted RME improve expansion efficacy, the biological basis underlying RME remains unclear, particularly concerning cell populations and tissue heterogeneity within the mid-palatal suture and the molecular mechanisms responding to mechanical forces during suture distraction osteogenesis. Preliminary studies have identified Gli1+ MSCs within mouse mid-palatal sutures, showing their proliferation in response to the RME mice model. The advent of large-scale single- cell RNA sequencing (scRNA-seq) technique has significantly advanced our ability to analyze cell heterogeneity in complex tissues. Osteoimmunology, which highlights the interaction between bone and immune systems, extends our research scope to immune cells, revealing their predominance in mid-palatal cell populations. Notably, neutrophils actively respond to mechanical stimuli, suggesting that MSCs and the immune microenvironment potentially influence RME efficacy. The aims of this proposal are: (1) To investigate the role of Gli1+ MSCs in response to mechanical stimuli during mid-palatal suture distraction osteogenesis, and (2) To identify the transcriptomic signatures of various cell populations in mouse mid-palatal suture, elucidating the interplay between MSCs and neutrophils during RME. This work may uncover previously unrecognized immune-MSC modulatory targets for maxillary expansion/distraction osteogenesis, paving the way for molecular modulation of suture growth and improved patient management, including identifying an immune molecular target that enhances mid-palatal suture growth with or without orthopedic approaches. Project Number: 1K08DE035170-01 | Fiscal Year: 2025 | NIH Institute/Center: National Institute of Dental and Craniofacial Research (NIDCR) | Principal Investigator: WENJING YU | Institution: UNIVERSITY OF PENNSYLVANIA, PHILADELPHIA, PA | Award Amount: $136,711 | Activity Code: K08 | Study Section: National Institute of Dental and Craniofacial Research Special Grants Review Committee[DSR] View on NIH RePORTER: https://reporter.nih.gov/project-details/11212032