Abstract
Recombinant human bone morphogenetic protein 2 (rhBMP-2) is one of the most potent osteogenic factors used to treat bone loss. However, at higher doses, rhBMP-2 does not necessarily increase bone formation but rather increases the incidence of adverse side effects. Here, we investigated whether umbilical cord mesenchymal stem cell (UCMSC)-derived nanovesicles (NVs) further increase the in vivo bone formation at high doses of rhBMP-2. In the presence of UCMSC-derived NVs, proliferation, migration, and tube formation of human umbilical vein endothelial cells were stimulated in vitro. Furthermore, migration and osteogenesis of human bone marrow-derived mesenchymal stem cells were stimulated. To examine the efficacy of UCMSC-derived NVs on in vivo bone formation, collagen sponges soaked with rhBMP-2 and UCMSC-derived NVs were used in athymic nude mice with calvarial defects. At a high rhBMP-2 dosage (500 ng/mL), UCMSC-derived NVs significantly promoted bone formation in calvarial defects; however, the UCMSC-derived NVs alone did not induce in vivo bone formation. Our results indicate that UCMSC-derived NVs can potentiate the bone formation efficacy of rhBMP-2 at a high dosage.
Highlights
Bone loss occurs via trauma and surgical procedures [1]
We demonstrated that recombinant human bone morphogenetic protein 2 (rhBMP-2) in combination with umbilical cord mesenchymal stem cell (UCMSC)-derived NVs increased in vivo bone formation efficacy compared with that of rhBMP-2 alone in a mouse calvaria defect model
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Summary
Bone loss occurs via trauma and surgical procedures [1]. If the bone defect is too large to spontaneously heal, bone regeneration needs to promoted to repair the defect. Exosomes secreted from mesenchymal stem cells (MSCs) can promote the proliferation, migration, and tube formation of endothelial cells in vitro, angiogenesis in vivo [21,22,23,24], and in vivo bone regeneration [25,26,27]. We examined whether UCMSC-derived NVs further increase in vivo bone formation at high dose of rhBMP-2. We demonstrated that UCMSC-derived NVs promote the in vitro proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs). They promote the in vitro migration and osteogenesis of human bone marrow-derived MSCs (hBMSCs). CChhaarraacctteerriizzaattiioonn ooff uummbbiilliiccaall ccoorrdd mmeesseenncchhyymmaall sstteemm cceellll ((UUCCMMSSCC))--ddeerriivveedd nnaannoovveessiicclleess ((NNVVss)).. ((aa)) SScchheemmaattiicc iilllluussttrraattiioonn ooff UUCCMMSSCC--ddeerriivveedd NNVV ffaabbrriiccaattiioonn ffrroomm UUCCMMSSCCss.. Tnh=e3Mpaenr ng–rWouhpi.tnTehye tMesatnwna–sWuhseitdnefoyrtestsattwisatiscaulsaendafloyrsisst.antisstfiocralnaontasliygsniisfi. cnasnfto. r not significant
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