Extracellular Vesicles of Stem Cells to Prevent BRONJ

Watanabe, Junna; Saito, Kiyoshi; Urata, Yusuke; Toyama, Naoto; NAKAMICHI, Eiji; Hibi, Hideharu

doi:10.1177/0022034520906793

Cited by 34 publications

(32 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A recent study stated that extracellular vesicles released from mesenchymal stem cells (MSC-EVs) could prevent BRONJ. 32 However, MSC-EVs require much work to be extracted after mass cultivation of MSC. Direct isolation of sEV from adipose tissue, an easily accessible source of biological material, costs less time and money.…”

Section: Discussionmentioning

confidence: 99%

Small Extracellular Vesicles Derived from Adipose Tissue Prevent Bisphosphonate-Related Osteonecrosis of the Jaw by Promoting Angiogenesis

Huang

Wang

Tian

2021

IJN

View full text Add to dashboard Cite

Purpose There is no definitive treatment for bisphosphonate-related osteonecrosis of the jaw (BRONJ). Small extracellular vesicles derived from adipose tissue (sEV-AT) have been proved efficient at promoting tissue regeneration. The aim of this study was to evaluate the effects of sEV-AT administration on BRONJ-like lesions in rats. Methods Zoledronate (Zol) and dexamethasone (Dex) were subcutaneously administered to create a BRONJ rat model. Rats were randomly divided into three groups: 1) Control; 2) Zol+Dex; 3) sEV-AT. The maxillary left first molars were extracted two weeks after the first administration. In the sEV-AT group, sEV-AT were given intravenously every three days right after tooth extraction. We preformed occlusal view images, microcomputed tomography (µCT) and histological analysis to measure the regeneration of osseous and soft tissue in extraction sockets. Human umbilical vein endothelial cells (HUVECs) were isolated and cultured with endothelial cell medium (ECM). HUVECs were then divided into three groups: 1) Control: ECM; 2) Zol: ECM+Zol; 3) sEV-AT: ECM+Zol+sEV-AT. We evaluated the proliferation, tube formation and migration of HUVECs in each group. Results Rats treated with Zol+Dex showed BRONJ-like lesions including open wounds, necrotic bones, empty osteocyte lacunae and reduced osteoclasts. sEV-AT administration reduced BRONJ-like lesions by promoting soft tissue healing. µCT results showed that bone volume in extraction sockets in the sEV-AT group was larger than the Zol+Dex group. Histological analysis showed less necrotic bones and empty osteocyte lacunae in the sEV-AT group compared to the Zol+Dex group. Histological analysis also showed more osteoclasts, collagen fibers and blood vessels in the sEV-AT group compared to the Zol+Dex group. Furthermore, sEV-AT enhanced the proliferation, migration and tube formation of HUVECs which were inhibited by Zol. Conclusion Our findings indicate that sEV-AT prevent BRONJ in rats. Angiogenesis promotion contributes to the prevention of BRONJ.

show abstract

Section: Discussionmentioning

confidence: 99%

Small Extracellular Vesicles Derived from Adipose Tissue Prevent Bisphosphonate-Related Osteonecrosis of the Jaw by Promoting Angiogenesis

Huang

Wang

Tian

2021

IJN

View full text Add to dashboard Cite

show abstract

“…EVs from MSCs have been described as able to act on endothelial cells to deliver angiogenic signals [81], especially in hypoxic and ischemic conditions [82,83]. In the bone context, pro-angiogenic effects of MSC-derived EVs have been shown in an osteonecrosis model [84,85]. Angiogenic properties of MSC-EVs have not been explored yet in OS.…”

Section: Gebraad Et Al Isolated Evs From Lipopolysaccharide-activatementioning

confidence: 99%

The Osteosarcoma Microenvironment: A Complex but Targetable Ecosystem

Corre

Verrecchia

Crenn

et al. 2020

Cells

310

271

View full text Add to dashboard Cite

Osteosarcomas are the most frequent primary bone sarcomas, affecting mainly children, adolescents, and young adults, and with a second peak of incidence in elderly individuals. The current therapeutic management, a combined regimen of poly-chemotherapy and surgery, still remains largely insufficient, as patient survival has not improved in recent decades. Osteosarcomas are very heterogeneous tumors, both at the intra- and inter-tumor level, with no identified driver mutation. Consequently, efforts to improve treatments using targeted therapies have faced this lack of specific osteosarcoma targets. Nevertheless, these tumors are inextricably linked to their local microenvironment, composed of bone, stromal, vascular and immune cells and the osteosarcoma microenvironment is now considered to be essential and supportive for growth and dissemination. This review describes the different actors of the osteosarcoma microenvironment and gives an overview of the past, current, and future strategies of therapy targeting this complex ecosystem, with a focus on the role of extracellular vesicles and on the emergence of multi-kinase inhibitors.

show abstract

“…599,600 EVs have been used to treat bisphosphonate-related osteonecrosis of the jaw (BRONJ) through promotion of angiogenesis and bone regeneration in rats. 601 Future development in dental biomaterial may exploit this potent delivery mechanism of biomolecules. 602 Some key factors must be considered as materials move toward translation.…”

Section: Future Perspectives and Conclusionmentioning

confidence: 99%