The bone regenerative capacity of canine mesenchymal stem cells is regulated by site-specific multilineage differentiation

Abstract

Objectives Mesenchymal stem cells (MSCs) are promising therapies in dentistry due to their multipotent properties. Selecting donor MSCs is crucial because beagle dogs (canines) commonly used in pre-clinical studies have shown variable outcomes and it is unclear whether canine MSCs (cMSCs) are skeletal site-specific. This study tested whether jaw and long bone cMSCs have disparate in vitro and in vivo multilineage differentiation capabilities. Study Design Primary cMSCs were isolated from mandible (M-cMSCs) and femur (F-cMSCs) of four healthy Beagle dogs. Femur served as non-oral control. Clonogenic and proliferative abilities were assessed. In vitro osteogenic, chondrogenic, adipogenic and neural multilineage differentiation were correlated with in vivo bone regeneration and potential for clinical applications. Results M-cMSCs displayed two-fold increase in clonogenic and proliferative capacities relative to F-cMSCs (p =0.006). M-cMSCs in vitro osteogenesis based on alkaline phosphatase (p =0.04), bone sialoprotein (p =0.05), and osteocalcin (p =0.03), as well as adipogenesis (p =0.007), and chondrogenesis (p =0.009) were relatively higher and correlated with enhanced M-cMSC bone regenerative capacity. Neural expression markers, nestin and βIII-tubulin were not significantly different. Conclusions The enhanced differentiation and bone regenerative capacity of mandible MSCs may make them favorable donor graft materials for site-specific jaw bone regeneration.

LepR-Expressing Stem Cells Are Essential for Alveolar Bone Regeneration

“…This is partly due to the distinct structures of alveolar bone, characterized by compact, wide, and highly mineralized trabeculae and less bone marrow (Zhou et al 2018). In addition, several in vitro studies demonstrated that SSCs from alveolar bone have a strong osteogenic potential (Akintoye et al 2006; Bugueño et al 2017).…”

Desmoplastic fibroma of the jaw bones: A series of twenty-two cases

“…Therefore, bone lesions may display unique histological changes in the jawbones. Craniofacial bone development is different from long bones and that it develops from neural crest [27] , [13] , [10] , [28] , [29] . This difference may also be effective in immunostaining results.…”

“…Nestin is a class VI intermediate filament protein; it is known as a specific marker of neural or neural crest stem cells [10] , [13] , [27] , [28] , [29] . Nestin, which tends to be more strongly expressed in mandibular bone morphogenetic stem cells (R).…”

Bidirectional ephrinB2‑EphB4 signaling regulates the osteogenic differentiation of canine periodontal ligament stem cells

“…currently, the canine mandible defect model is widely used in preclinical studies (25)(26)(27). Notably, beagle dogs are recommended as potential animal models for medical testing due to their genetic, biological and behavioral characteristics that closely resemble those of humans; furthermore, numerous symptoms of human conditions can be replicated in dogs (28). Previous studies comparing canine and human dental mesenchymal stem cells have demonstrated that canine dPScs were able to differentiate into odontoblast-like cells exhibiting osteogenic potential similar to human dPScs (29).…”