Use of buccal fat pad-derived stem cells cultured on bioceramics for repair of critical-sized mandibular defects in healthy and osteoporotic rats

Abstract

Objective To compare new bone formation in mandibular symphysis critical-sized bone defects (CSBDs) in healthy and osteoporotic rats filled with bioceramics (BCs) with or without buccal fat pad mesenchymal stem cells (BFPSCs). Materials and methods Thirty-two adult female Sprague–Dawley rats were randomized to two groups (n = 16 per group): group 1 healthy and group 2 osteoporotic (with bilateral ovariectomy). The central portion of the rat mandibular symphysis was used as a physiological CSBD. In each group, eight defects were filled with BC (hydroxyapatite 60% and β-tricalcium phosphate 40%) alone and eight with BFPSCs cultured on BC. The animals were sacrificed at 4 and 8 weeks, and the mandibles were processed for micro-computed tomography to analyze radiological union and bone mineral density (BMD); histological analysis of the bone union; and immunohistochemical analysis, which included immunoreactivity of vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP-2). Results In both groups, CSBDs filled with BC + BFPSCs showed greater radiological bone union, BMD and histological bone union, and more VEGF and BMP-2 positivity, compared with CSBDs treated with BC alone at 4 and 8 weeks. Conclusions The application of BFPSCs cultured on BCs improves bone regeneration in CSBDs compared with BCs alone in healthy and osteoporotic rats. Clinical relevance Our results may aid bone regeneration of maxillofacial CSBDs of both healthy and osteoporotic patients, but further studies are necessary.

Effects of periodontal cells‐derived extracellular vesicles on mesenchymal stromal cell function

“…Thus, BFP‐MSCs have the potential for a wide range of medical applications and are being actively researched for their therapeutic potential, i.e. alveolar bone regeneration 26,27 . All three EVs subtypes were internalised in BFP‐MSCs from 4 h to 7 days.…”

“…alveolar bone regeneration. 26,27 All three EVs subtypes were internalised in BFP-MSCs from 4 h to 7 days. sEV promoted cell proliferation and migration compared to the EV-free group, as observed previously for PDLCs-sEV 24,46 and GMSCs-sEV 18 and in vivo osteogenesis mediated by PDLCs-sEV and GF/GMSCs-sEV.…”

“…However, there have been few studies that have investigated the regenerative potential of EVs produced by alveolar bone‐derived osteoblasts, as well as the comparison of the effects of hPDLCs‐EVs, hGFs‐EVs and hOBs‐EVs on the differentiation fate of human buccal fat pad‐mesenchymal stromal cells (hBFP‐MSCs, a recently discovered source of multipotent MSCs within the oral cavity 26 ). BFP‐MSCs possess characteristics similar to those of MSCs derived from bone marrow or adipose tissue, with the additional benefits of being easily accessible from a highly abundant intraoral tissue source and having minimal discomfort after retrieval 26–28 . As such, hBFP‐MSCs are an attractive source for cell therapies or cell‐based oral bioengineering therapies for bone regeneration, 26,29,30 and EVs are a potential strategy to facilitate lineage‐specific differentiation prior to implantation (e.g.…”

“…Studies showed that sEVs derived from bone marrow-derived MSCs (BMSCs), [15][16][17] GM-SCs [18][19][20] and PDLCs [21][22][23][24][25] have demonstrated elevated osteogenesis and anti-inflammatory capability in the context of bone regeneration in vitro and in vivo. However, there have been few studies that have investigated the regenerative potential of EVs produced by alveolar bone-derived osteoblasts, as well as the comparison of the effects of hPDLCs-EVs, hGFs-EVs and hOBs-EVs on the differentiation fate of human buccal fat pad-mesenchymal stromal cells (hBFP-MSCs, a recently discovered source of multipotent MSCs within the oral cavity 26 ). BFP-MSCs possess characteristics similar to those of MSCs derived from bone marrow or adipose tissue, with the additional benefits of being easily accessible from a highly abundant intraoral tissue source and having minimal discomfort after retrieval.…”

“…BFP-MSCs possess characteristics similar to those of MSCs derived from bone marrow or adipose tissue, with the additional benefits of being easily accessible from a highly abundant intraoral tissue source and having minimal discomfort after retrieval. [26][27][28] As such, hBFP-MSCs are an attractive source for cell therapies or cellbased oral bioengineering therapies for bone regeneration, 26,29,30 and EVs are a potential strategy to facilitate lineage-specific differentiation prior to implantation (e.g. sEVs from hPDLCs driving cellular osteogenic differentiation, reviewed in Ref.…”