Human fetal mesenchymal stem cell secretome enhances bone consolidation in distraction osteogenesis

Xu, Jia; Wang, Bin; Sun, Yuxin; Wu, Tianyi; Liu, Yang; Zhang, Jinfang; Lee, Wayne; Pan, Xiaohua; Chai, Yimin; Li, Gang

doi:10.1186/s13287-016-0392-2

Cited by 67 publications

(67 citation statements)

References 37 publications

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“…Various doses of dBMSC‐exos and nBMSC‐exos were added to OIM in the experimental group, whereas cells in the control group were cultured in OIM without exosomes. Osteogenic differentiation was assessed by alkaline phosphatase (ALP) staining and ALP activity on day 3, quantitative reverse transcription polymerase chain reaction (qRT‐PCR), WB, and immunofluorescence (IF) on day 7, and alizarin red S staining on day 14 according to our established protocol .…”

Section: Methodsmentioning

confidence: 99%

Impaired Bone Regenerative Effect of Exosomes Derived from Bone Marrow Mesenchymal Stem Cells in Type 1 Diabetes

Zhu

Jia

Wang

et al. 2019

Stem Cells Translational Medicine

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Stem cell‐derived exosomes have exhibited promise for applications in tissue regeneration. However, one major problem for stem cell‐derived exosome therapies is identifying appropriate source cells. In the present study, we aimed to compare the bone regenerative effect of exosomes secreted by bone marrow mesenchymal stem cells (BMSCs) derived from type 1 diabetes rats (dBMSC‐exos) and exosomes secreted by BMSCs derived from normal rats (nBMSC‐exos). BMSCs were isolated from rats with streptozotocin‐induced diabetes and normal rats. dBMSC‐exos and nBMSC‐exos were isolated by an ultracentrifugation method and identified. The effects of dBMSC‐exos and nBMSC‐exos on the proliferation and migration of BMSCs and human umbilical vein endothelial cells (HUVECs) were investigated. The effects of exosomes on the osteogenic differentiation of BMSCs and the angiogenic activity of HUVECs were compared. Finally, a rat calvarial defect model was used to compare the effects of exosomes on bone regeneration and neovascularization in vivo. In vitro, dBMSC‐exos and nBMSC‐exos both enhanced the osteogenic differentiation of BMSCs and promoted the angiogenic activity of HUVECs, but nBMSC‐exos had a greater effect than dBMSC‐exos. Similarly, in vivo, both dBMSC‐exos and nBMSC‐exos promoted bone regeneration and neovascularization in rat calvarial defects, but the therapeutic effect of nBMSC‐exos was superior to that of dBMSC‐exos. The present study demonstrates for the first time that the bone regenerative effect of exosomes derived from BMSCs is impaired in type 1 diabetes, indicating that for patients with type 1 diabetes, the autologous transplantation of BMSC‐exos to promote bone regeneration may be inappropriate. stem cells translational medicine 2019;8:593–605

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Section: Methodsmentioning

confidence: 99%

Impaired Bone Regenerative Effect of Exosomes Derived from Bone Marrow Mesenchymal Stem Cells in Type 1 Diabetes

Zhu

Jia

Wang

et al. 2019

Stem Cells Translational Medicine

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“…Secretome-based approaches using CM may present osteogenic potential advantages over living cells regarding manufacturing, storage, handling, product shelf life and their potential as a ready-to-go biological therapeutic agent [34][35][36][37][38][39][40][41].…”

Section: Discussionmentioning

confidence: 99%

Role of Mesenchymal Stem Cell-Conditioned Medium (MSC-CM) in the Bone Regeneration: A Systematic Review from 2007-2018

Dilogo

Fiolin

2019

ARRB

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Background: The therapeutic value of mesenchymal stem cells (MSCs) in tissue engineering and regenerative medicine is attributable in part to paracrine pathways triggered by several secreted factors secreted into culture media. The secreted factor here is known as the conditioned medium (CM) or secretome. Objectives: This review is aimed to investigate and summarise the in-vitro, pre-clinical in-vivo studies regarding the role of CM-MSC in bone regeneration from 2007 until 2018 Data Sources: A systematic literature search on PubMed, MEDLINE, OVID, Scopus and Cochrane library was carried out by using search terms: Secretome, conditioned medium, mesenchymal stem cell, bone healing, osteogenic, osteogenesis. Methods: A total of 611 articles were reviewed. Ten articles were identified as relevant for this systematic literature review. Results: Three tables of studies were constructed for in vitro studies and in-vivo studies. Conclusion: All of the included in-vitro studies and in-vivo studies have shown a promoting effect of bone regeneration at various stages. Although there are no clinical studies regarding the use of CM-MSC in the human bone regeneration that have been conducted, transplantation of secretome has shown a promising result in the acceleration of bone healing process.

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“…Reconstruction of low and high density mineralized bone were performed using different thresholds (low attenuation=158, high attenuation=211) following the previously published protocol with a small modification. 33 The high-density tissues represented the newly formed highly mineralized bone, while the low ones represented the newly formed callus. Bone volume (BV), tissue volume (TV) and BV/TV of each specimen was recorded for analysis.…”

Section: Methodsmentioning

confidence: 99%

MicroRNA-378 suppressed osteogenesis of mesenchymal stem cells and impaired bone formation via inactivating Wnt/β-catenin signaling

Zhang

Shi

et al. 2019

Preprint

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37MicroRNAs (miRNAs) have been reported to serve as silencers to repress gene 38 expression at post-transcriptional level. Multiple miRNAs have been demonstrated to 39 play important roles in osteogenesis. MiR-378, a conserved miRNA, was reported to 40 mediate bone metabolism and influence bone development, but the detailed function 41 and underlying mechanism remain obscure. In this study, the miR-378 transgenic (TG) 42 mouse was developed to study the role of miR-378 in osteogenic differentiation as 43 well as bone formation. The abnormal bone tissues and impaired bone quality were 44 displayed in the miR-378 TG mice, and a delayed healing effect was observed during 45 bone fracture of the miR-378 TG mice. The osteogenic differentiation of MSCs 46 derived from this TG mouse was also inhibited. We also found that miR-378 mimics 47 suppressed while anti-miR-378 promoted osteogenesis of human MSCs. Two Wnt 48 family members Wnt6 and Wnt10a were identified as bona fide targets of miR-378, 49 and their expression were decreased by this miRNA, which eventually induced the 50 inactivation of Wnt/β-catenin signaling. Finally, the sh-miR-378 modified MSCs were 51 locally injected into the fracture sites in an established mouse fracture model. The 52 results indicated that miR-378 inhibitor therapy could promote bone formation and 53 stimulate healing process in vivo. In conclude, miR-378 suppressed osteogenesis and 54 bone formation via inactivating Wnt/β-catenin signaling, suggesting miR-378 may be 55 a potential therapeutic target for bone diseases.56 Key words: miR-378; mesenchymal stem cells; osteogenesis; Wnt/β-catenin 57 signaling; bone formation 58 59 Bone regeneration is very important for the recovery of some diseases including 60 osteoporosis and bone fracture trauma. It is a multiple step and multiple gene involved 61 complex process, including osteoblast-mediated bone formation and 62 osteoclast-mediated bone resorption. During this process, mesenchymal stem cells 63 (MSCs) gradually differentiate into osteoblasts, which produce a variety of 64 extracellular matrix and thus induce the initiation of bone formation. Hence, 65 improving the osteoblast differentiation of MSCs is crucial for the development of 66 therapeutic strategy for bone diseases. 67 Over the past few years, microRNAs (miRNAs) have emerged as gene silencers to 68 suppress gene expression at post-transcriptional level. Multiple miRNAs have been 69 demonstrated to play important roles in biological activities including osteogenic 70 differentiation and skeletal development. For example, miR-26a, miR-29b, miR-125b, 71 miR-133, miR-135 and miR-196a, have been reported to be involved in 72 osteogenesis. 1-5 Our previous reports also demonstrated that miR-20a and 20b 73 promoted whereas miR-637 suppressed osteoblast differentiation. 6-7 Therefore, 74 miRNAs have been considered as potential candidates to mediate osteogenic 75 differentiation and may be acted as therapeutic targets for bone regeneration.76 MiR-378, which is derived from a ...

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Human fetal mesenchymal stem cell secretome enhances bone consolidation in distraction osteogenesis

Cited by 67 publications

References 37 publications

Impaired Bone Regenerative Effect of Exosomes Derived from Bone Marrow Mesenchymal Stem Cells in Type 1 Diabetes

Impaired Bone Regenerative Effect of Exosomes Derived from Bone Marrow Mesenchymal Stem Cells in Type 1 Diabetes

Role of Mesenchymal Stem Cell-Conditioned Medium (MSC-CM) in the Bone Regeneration: A Systematic Review from 2007-2018

MicroRNA-378 suppressed osteogenesis of mesenchymal stem cells and impaired bone formation via inactivating Wnt/β-catenin signaling

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