<b><i>Retracted:</i></b> Endothelial/Mesenchymal Stem Cell Crosstalk Within Bioprinted Cocultures

Santoro, Marco; Awosika, Tolulope O; Snodderly, Kirstie; Hurley-Novatny, Amelia C; Lerman, Max J.; Fisher, John P.

doi:10.1089/ten.tea.2019.0175

Cited by 6 publications

(4 citation statements)

References 36 publications

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“…12 c. The synergistic effects of multiple growth factors from the composite scaffolds promote the expressions of VEGF, and enhance VEGF paracrine in the defect site, which improves HUVECs proliferation, differentiation, and tubular structure formation. Previously, communication and functional connection of osteoblast-vascular cells during bone development was found to be stimulated by localized secretion of paracrine signaling factors, such as VEGF and BMP-2 [ [53] , [54] , [55] ]. In accordance with this study, our dual delivery system stimulated the BMSCs-secreted VEGF, which promoted the proliferation and angiogenic differentiation of HUVECs.…”

Section: Discussionmentioning

confidence: 99%

Controlled growth factor delivery system with osteogenic-angiogenic coupling effect for bone regeneration

Kang

et al. 2021

Journal of Orthopaedic Translation

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Objective Bone regeneration involves a coordinated cascade of events that are regulated by several cytokines and growth factors, among which bone morphogenic protein-2 (BMP-2), vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2) play important roles. In this study, we investigated the effects of dual release of the three growth factors on bone regeneration in femur defects. Methods A composite consisting of Gelatin microparticles loaded with VEGF/FGF-2 and poly(lactic-co-glycolic acid)-poly(ethylene glycol)-carboxyl (PLGA-PEG-COOH) microparticles loaded with BMP-2 encapsulated in a nano hydroxyapatite-poly actic-co-glycolic acid (nHA-PLGA) scaffold was prepared for the dual release of the growth factors. Results On the 14th day, decreased release rate of BMP-2 compared with FGF-2 and VEGF was observed. However, after 14 days, compared to FGF-2 and VEGF, BMP-2 showed an increased release rate. Controlled dual release of BMP-2 and VEGF, FGF-2 resulted in a significant osteogenic differentiation of bone mesenchymal stem cells (BMSCs). Moreover, effects of the composite scaffold on functional connection of osteoblast-vascular cells during bone development were evaluated. The synergistic effects of dual delivery of growth factors were shown to promote the expression of VEGF in BMSCs. Increased secretion of VEGF from BMSCs promoted the proliferation and angiogenic differentiation of human umbilical vein endothelial cells (HUVECs) in the co-culture system. At 12 weeks after implantation, blood vessel and bone formation were analyzed by micro-CT and histology. The composite scaffold significantly promoted the formation of blood vessels and new bone in femur defects. Conclusions These findings demonstrate that dual delivery of angiogenic factors and osteogenic factors from Gelatin and PLGA-PEG-COOH microparticles-based composite scaffolds exerted an osteogenic-angiogenic coupling effect on bone regeneration. This approach will inform on the development of appropriate designs of high-performance bioscaffolds for bone tissue engineering.

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Section: Discussionmentioning

confidence: 99%

Controlled growth factor delivery system with osteogenic-angiogenic coupling effect for bone regeneration

Kang

et al. 2021

Journal of Orthopaedic Translation

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“…In general, findings are positive as MSCs promote ECs-mediated angiogenesis and ECs may regulate the migration and differentiation of MSCs [ 21 ]. Accordingly, their coculture has been widely employed to ameliorate repairing efficacy via forming vasculature and inducing vessel ingrowth prior to and after bone grafting, respectively [ 6 ]. Nevertheless, unlike the impact of MSCs on ECs, which has been widely described, less is known on the inverse effects.…”

Section: Discussionmentioning

confidence: 99%

“…During the embryonic and postnatal periods, intimate physical proximity exists between blood vessels and osteoprogenitors, implying a close relationship between endothelial cells (ECs) and MSCs [ 5 ]. Indeed, the crosstalk of ECs and MSCs has been widely documented and exploited to ameliorate blood supply and expedite tissue regeneration [ 6 ]. Initially, attention was given to the transdifferentiation of MSCs into ECs or the regulatory effects of MSCs on ECs [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Endothelial Cells Promote Migration of Mesenchymal Stem Cells via PDGF-BB/PDGFRβ-Src-Akt in the Context of Inflammatory Microenvironment upon Bone Defect

Hou

Zhou

et al. 2022

Stem Cells International

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Homing of mesenchymal stem cells (MSCs) to the defect site is indispensable for bone repair. Local endothelial cells (ECs) can recruit MSCs; however, the mechanism remains unclear, especially in the context of the inflammatory microenvironment. This study was aimed to investigate the role of ECs in MSCs migration during the inflammatory phase of bone repair. The inflammatory microenvironment was mimicked in vitro via adding a cytokine set (IL-1β, IL-6, and TNF-α) to the culture medium of ECs. The production of PDGF-BB from ECs was measured by ELISA. Transwell and wound healing assays were employed to assess MSCs migration toward ECs and evaluate the implication of PDGF-BB/PDGFRβ. A series of shRNA and pathway inhibitors were used to screen signal molecules downstream of PDGF-BB/PDGFRβ. Then, mouse models of femoral defects were fabricated and DBM scaffolds were implanted. GFP+ MSCs were injected via tail vein, and the relevance of PDGF-BB/PDGFRβ, as well as screened signal molecules, in cell homing was further verified during the early phase of bone repair. In the mimicked inflammatory microenvironment, MSCs migration toward ECs was significantly promoted, which could be abrogated by pdgfrb knockout in MSCs. Inhibition of Src or Akt led to negative effects analogous to pdgfrb knockout. Blockade of JNK, MEK, and p38 MAPK had no impact. Meanwhile, the secretion of PDGF-BB from ECs was evidently motivated by the inflammatory microenvironment. Adding recombinant PDGF-BB protein to the culture medium of ECs phenocopied the inflammatory microenvironment with regard to attracting MSCs, which was abolished by pdgfb, src, or akt in MSCs. Moreover, pdgfb knockout suppressed the expression and phosphorylation of Src and Akt in migrating MSCs. Src knockout impaired Akt expression but not vice versa. In vivo, reduced infiltration of CD31+ ECs was correlated with diminished PDGF-BB in local defect sites, and silencing pdgfb, src, or akt in MSCs markedly hampered cell homing. Together, these findings suggest that in the inflammatory microenvironment, MSCs migrate toward ECs via PDGF-BB/PDGFRβ and the downstream Src-Akt signal pathway.

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“…TGF-β treatment on bone-marrow MSCs has been shown to increase early SMCs markers α smooth muscle actin (SMA) and H1-calponin expression [79]. The impact of MSC on angiogenesis is mostly likely exerted in a ratio-dependent manner, including angiogenic gene expression [80], cell metabolic activity [81], and alteration of inflammatory response by ECs stimulated with TNF or with IL-1 [82]. The heterogeneity nature of MSCs and individual to individual variance are the major obstacles that impede the clinical translation of MSCs.…”

Section: Human Mesenchymal Stem Cellmentioning

confidence: 99%

Vascularization in tissue engineering: fundamentals and state-of-art

et al. 2020

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Vascularization is among the top challenges that impede the clinical application of engineered tissues. This challenge has spurred tremendous research endeavor, defined as vascular tissue engineering (VTE) in this article, to establish a pre-existing vascular network inside the tissue engineered graft prior to implantation. Ideally, the engineered vasculature can be integrated into the host vasculature via anastomosis to supply nutrient to all cells instantaneously after surgery. Moreover, sufficient vascularization is of great significance in regenerative medicine from many other perspectives. Due to the critical role of vascularization in successful tissue engineering, we aim to provide an up-to-date overview of the fundamentals and VTE strategies in this article, including angiogenic cells, biomaterial/bio-scaffold design and bio-fabrication approaches, along with the reported utility of vascularized tissue complex in regenerative medicine. We will also share our opinion on the future perspective of this field.

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Retracted: Endothelial/Mesenchymal Stem Cell Crosstalk Within Bioprinted Cocultures

Cited by 6 publications

References 36 publications

Controlled growth factor delivery system with osteogenic-angiogenic coupling effect for bone regeneration

Controlled growth factor delivery system with osteogenic-angiogenic coupling effect for bone regeneration

Endothelial Cells Promote Migration of Mesenchymal Stem Cells via PDGF-BB/PDGFRβ-Src-Akt in the Context of Inflammatory Microenvironment upon Bone Defect

Vascularization in tissue engineering: fundamentals and state-of-art

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