Bone regeneration capacities of alveolar bone mesenchymal stem cells sheet in rabbit calvarial bone defect

Abstract

Mesenchymal stem cells sheets have been verified as a promising non-scaffold strategy for bone regeneration. Alveolar bone marrow mesenchymal stem cells, derived from neural crest, have the character of easily obtained and strong multi-differential potential. However, the bone regenerative features of alveolar bone marrow mesenchymal stem cells sheets in the craniofacial region remain unclear. The purpose of the present study was to compare the osteogenic differentiation and bone defect repairment characteristics of bone marrow mesenchymal stem cells sheets derived from alveolar bone (alveolar bone marrow mesenchymal stem cells) and iliac bone (Lon-bone marrow mesenchymal stem cells) in vitro and in vivo. Histology character, osteogenic differentiation, and osteogenic gene expression of human alveolar bone marrow mesenchymal stem cells and Lon-bone marrow mesenchymal stem cells were compared in vitro. The cell sheets were implanted in rabbit calvarial defects to evaluate tissue regeneration characteristics. Integrated bioinformatics analysis was used to reveal the specific gene and pathways expression profile of alveolar bone marrow mesenchymal stem cells. Our results showed that alveolar bone marrow mesenchymal stem cells had higher osteogenic differentiation than Lon-bone marrow mesenchymal stem cells. Although no obvious differences were found in the histological structure, fibronectin and integrin β1 expression between them, alveolar-bone marrow mesenchymal stem cells sheet exhibited higher mineral deposition and expression levels of osteogenic marker genes. After being transplanted in the rabbit calvarial defects area, the results showed that greater bone volume and trabecular thickness regeneration were found in bone marrow mesenchymal stem cells sheet group compared to Lon-bone marrow mesenchymal stem cells group at both 4 weeks and 8 weeks. Finally, datasets of bone marrow mesenchymal stem cells versus Lon-bone marrow mesenchymal stem cells, and periodontal ligament mesenchymal stem cells (another neural crest derived mesenchymal stem cells) versus umbilical cord mesenchymal stem cells were analyzed. Total 71 differential genes were identified by overlap between the 2 datasets. Homeobox genes, such as LHX8, MKX, PAX9, MSX, and HOX, were identified as the most significantly changed and would be potential specific genes in neural crest mesenchymal stem cells. In conclusion, the Al-bone marrow mesenchymal stem cells sheet-based tissue regeneration appears to be a promising strategy for craniofacial defect repair in future clinical applications.

Fabrication and Characterization of Collagen/PVA Dual-Layer Membranes for Periodontal Bone Regeneration

“…In addition to the collagen based artificial scaffolds or membranes, it is worthy to mention another promising type of scaffold, based more on the extracellular matrix as well as cells, named as “cell sheet” ( Chen et al, 2019 ; Lu et al, 2019 ). Cell sheet was efficaciously utilized in the regeneration of bone and periodontal ligament-like tissues as shown by recent works ( Dong et al, 2020 ; Liu Y. et al, 2020 ). Promising as it demonstrated to be, cell sheet manufacture requires high manipulation skills to ensure the quality control ( Chen et al, 2019 ), while the current artificial Col/PVA membrane offers the superiority in relatively easy manufacturing with controllability.…”

Neural crest-like stem cells for tissue regeneration

“…A recent study demonstrated that adult manidular skeletal stem cells activated an embryonic NC cell‐like gene regulatory program that is dependent on the focal adhesion kinase pathway during distraction osteogenesis, 120 enabling these cells to acquire a more plastic, developmental state that aids in jaw bone regeneration. In addition, alveolar bone‐derived MSCs 121 display high osteogenic potential and promote ectopic bone formation in vivo, 122–125 providing a more accessible MSC source compared with the iliac crest.…”

Efficacy of chitinase-3-like protein 1 as an in vivo bone formation predictable marker of maxillary/mandibular bone marrow stromal cells

“…Although it has been reported that CHI3L1 is not synthesized in undifferentiated iliac MSCs [ 37 ], some undifferentiated MBMSCs synthesized and secreted CHI3L1 in this study. MBMSCs have lower chondrogenic and adipogenic differentiation capacity [ 9 ] and greater osteogenic differentiation capacity than iliac MSCs [ 38 , 39 ]. In addition, MBMSCs and iliac MSCs have been reported to have different gene expression according to DNA microarray analysis [ 40 ].…”