A Murine Calvarial Defect Model for the Investigation of the Osteogenic Potential of Newborn Umbilical Cord Mesenchymal Stem Cells in Bone Regeneration

Abstract

left lip and/or palate (CLP), is the most common craniofacial congenital disability, affecting an estimated one in 700 live births. 1,2 Most patients with complete CLP also have an alveolar cleft. The mainstay of alveolar cleft repair (ACR) at many institutions is secondary alveolar bone grafting (ABG), with autogenous iliac crest bone graft (ICBG) being the standard graft material. However, this procedure is associated with significant donor-site morbidity, including hematoma, pain, and disfiguring scars. 3Background: The standard graft material for alveolar cleft repair (ACR) is autogenous iliac crest. A promising alternative potential graft adjunct-newborn human umbilical cord mesenchymal stem cells (h-UCMSCs)-has yet to be explored in vivo. Their capacity for self-renewal, multipotent differentiation, and proliferation allows h-UCMSCs to be harnessed for regenerative medicine. This study sought to evaluate the efficacy of using tissue-derived h-UCMSCs and their osteogenic capabilities to improve ACR in a murine model. Methods: Foxn1 mice were separated into three groups with the following calvarial defects: no treatment (empty defect; n = 6), poly(D,L-lactide-co-glycolide) (PLGA) scaffold (n = 6), or h-UCMSCs with PLGA (n = 4). Bilateral 2-mmdiameter parietal bone critical-sized defects were created using a dental drill. Microcomputed tomography (microCT) imaging was performed 1, 2, 3, and 4 weeks postoperatively. The mice were euthanized 4 weeks postoperatively for RNAScope, immunohistochemical, and histological analysis. Results: No mice experienced complications during the follow-up period. MicroCT imaging and histological analysis demonstrated that the no-treatment and PLGA-only defects remained patent without significant defect size differences across groups. In contrast, the h-UCMSCs with PLGA group had significantly greater bone fill on microCT and histological analysis. Conclusions: This study demonstrates a successful calvarial defect model for the investigation of h-UCMSC-mediated osteogenesis and bone repair. Evidence reveals that PLGA alone has neither short-term effects on bone formation nor any unwanted side effects, making it an attractive scaffold. Further investigation using h-UCMSCs with PLGA in larger animals is warranted to advance future translation to patients requiring ACR.

Whole-transcriptome profiling reveals potential biomarkers for the reversal of thymic epithelial cell senescence by umbilical cord mesenchymal stem cells

“…Because of their high self-renewal capacity, capacity to fight oxidative stress and inflammation, and capacity to release a variety of cytokines, UCMSCs have been suggested to be crucial for reversing thymic aging [17]. In addition, TECs are fundamental to the three-dimensional structure of the thymus and are crucial for organ growth [18,19].…”