Bone Regeneration Potential of Stem Cells Derived from Periodontal Ligament or Gingival Tissue Sources Encapsulated in RGD-Modified Alginate Scaffold

Abstract

Mesenchymal stem cells (MSCs) provide an advantageous alternative therapeutic option for bone regeneration in comparison to current treatment modalities. However, delivering MSCs to the defect site while maintaining a high MSC survival rate is still a critical challenge in MSC-mediated bone regeneration. Here, we tested the bone regeneration capacity of periodontal ligament stem cells (PDLSCs) and gingival mesenchymal stem cells (GMSCs) encapsulated in a novel RGD-(arginine-glycine-aspartic acid tripeptide) coupled alginate microencapsulation system in vitro and in vivo. Five-millimeter-diameter critical-size calvarial defects were created in immunocompromised mice and PDLSCs and GMSCs encapsulated in RGD-modified alginate microspheres were transplanted into the defect sites. New bone formation was assessed using microcomputed tomography and histological analyses 8 weeks after transplantation. Results confirmed that our microencapsulation system significantly enhanced MSC viability and osteogenic differentiation in vitro compared with non-RGD-containing alginate hydrogel microspheres with larger diameters. Results confirmed that PDLSCs were able to repair the calvarial defects by promoting the formation of mineralized tissue, while GMSCs showed significantly lower osteogenic differentiation capability. Further, results revealed that RGD-coupled alginate scaffold facilitated the differentiation of oral MSCs toward an osteoblast lineage in vitro and in vivo, as assessed by expression of osteogenic markers Runx2, ALP, and osteocalcin. In conclusion, these results for the first time demonstrated that MSCs derived from orofacial tissue encapsulated in RGD-modified alginate scaffold show promise for craniofacial bone regeneration. This treatment modality has many potential dental and orthopedic applications.

Evaluation of the effects of Angelicae dahuricae radix on the morphology and viability of mesenchymal stem cells

“…There is increasing interest in mesenchymal stem cells provide as they are an advantageous alternative therapeutic option for tissue regeneration in comparison to current treatment modalities (17). Previous reports showed that stem cells derived from the gingiva exhibited colony-forming abilities, plastic adherence and multilineage differentiation (osteogenic, adipogenic, chondrogenic) potency, and expressed CD44, CD73, CD90 and CD105 (18).…”

Treatment of intrabony defects with modified perforated membranes in aggressive periodontitis: a 12-month randomized controlled trial

“…GMSCs showed few inflammation-related changes when incubated with proinflammatory mediators (TNF-α, IL-1β), which suggested good response to unfavorable environmental conditions [10]. A bone regenerative capacity of GMSCs has been confirmed by multiple studies, as these cells were able to repair the critical size mandibular/calvarial defects in animals [11][12][13]. Moreover, the transplanted GMSCs proved a significant periodontal regenerative potential in vivo, with newly formed alveolar bone, cementum, and periodontal ligament fibers [14][15][16].…”

Craniomaxillofacial Sources of Mesenchymal Stem Cells: A Brief Review

“…Furthermore, PDLSC microencapsulation in RGD-coupled alginate enhanced MSC viability, proliferation and osteogenic differentiation both in vitro and in vivo [41] . The combination of PDLSC with MSC demonstrated greater reossification when placed in a mouse calvarial defect model [41] .…”