Transplanted blood-derived endothelial progenitor cells (EPC) enhance bridging of sheep tibia critical size defects

Rozen, Nimrod; Bick, Tova; Bajayo, Alon; Shamian, Ben; Schrift-Tzadok, Michal; Gabet, Yankel; Yayon, Avner; Bab, Itai; Soudry, Michael; Lewinson, Dina

doi:10.1016/j.bone.2009.07.085

Cited by 90 publications

(84 citation statements)

References 25 publications

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“…bone repair in mice [27], rat [28], and ovine models [29]. Our key finding was a potentiated osteogenic response of hfMSC in vitro via paracrine signaling, where soluble factors present in ECFC-CM exerted a profound effect on osteogenic differentiation of hfMSC.…”

Section: Discussionmentioning

confidence: 74%

Vasculogenic and Osteogenesis-Enhancing Potential of Human Umbilical Cord Blood Endothelial Colony-Forming Cells

et al. 2012

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Umbilical cord blood‐derived endothelial colony‐forming cells (UCB‐ECFC) show utility in neovascularization, but their contribution to osteogenesis has not been defined. Cocultures of UCB‐ECFC with human fetal‐mesenchymal stem cells (hfMSC) resulted in earlier induction of alkaline phosphatase (ALP) (Day 7 vs. 10) and increased mineralization (1.9×; p < .001) compared to hfMSC monocultures. This effect was mediated through soluble factors in ECFC‐conditioned media, leading to 1.8–2.2× higher ALP levels and a 1.4–1.5× increase in calcium deposition (p < .01) in a dose‐dependent manner. Transcriptomic and protein array studies demonstrated high basal levels of osteogenic (BMPs and TGF‐βs) and angiogenic (VEGF and angiopoietins) regulators. Comparison of defined UCB and adult peripheral blood ECFC showed higher osteogenic and angiogenic gene expression in UCB‐ECFC. Subcutaneous implantation of UCB‐ECFC with hfMSC in immunodeficient mice resulted in the formation of chimeric human vessels, with a 2.2‐fold increase in host neovascularization compared to hfMSC‐only implants (p = .001). We conclude that this study shows that UCB‐ECFC have potential in therapeutic angiogenesis and osteogenic applications in conjunction with MSC. We speculate that UCB‐ECFC play an important role in skeletal and vascular development during perinatal development but less so in later life when expression of key osteogenesis and angiogenesis genes in ECFC is lower. Stem Cells2012;30:1911–1924

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Section: Discussionmentioning

confidence: 74%

Vasculogenic and Osteogenesis-Enhancing Potential of Human Umbilical Cord Blood Endothelial Colony-Forming Cells

et al. 2012

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“…Although bone possesses endogenous self-repair mechanisms [4][5][6][7][8], in conditions such as impaired blood supply, excessive damage to the periosteum, inadequate immobilization, infection at the affected area, mineral and vitamin deficiencies, underlying diseases and side effects of certain medications and radiation, the enhancement of the regenerative processes is necessary to ensure the rapid and adequate restoration of skeletal functions [9][10][11]. The standard therapy to treat bone fractures/defects includes mechanical support either via cast and/or mechanical devices (e.g.…”

Section: Bone Regenerative Strategies: Biomolecules Cells and Biomatmentioning

confidence: 99%

The rational use of animal models in the evaluation of novel bone regenerative therapies

Perić¹,

Dumić-Čule²,

Grčević³

et al. 2015

Bone

125

116

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“…(34,35) More direct evidence for a putative contribution of vascularderived cells to bone formation is that circulating endothelial cells can acquire an osteoblast-like phenotype in vitro and enhance fracture healing when applied locally. (36) CXCR4þ CXCR2À (54) or CD14þ cells that lose CD14 positivity with time in culture. (16) With a BMP-inducible model of ectopic bone formation and a Cre-lox system to generate myeloid-restricted b-galactosidase expression, specific activity was detected in newly formed chondrocytes.…”

Section: Cells Belonging To the Vascular Lineagementioning

confidence: 99%

Circulating osteogenic cells: Implications for injury, repair, and regeneration

Pignolo

Kassem

2011

Journal of Bone and Mineral Research

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The aim of this review is to provide a critical reading of recent literature pertaining to the presence of circulating, fluid-phase osteoblastic cells and their possible contribution to bone formation. We have termed this group of cells collectively as circulating osteogenic precursor (COP) cells. We present evidence for their existence, methods used for their isolation and identification, possible physiological and pathophysiological roles, cellular origins, and possible mechanisms for their migration to target tissues. ß

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Transplanted blood-derived endothelial progenitor cells (EPC) enhance bridging of sheep tibia critical size defects

Cited by 90 publications

References 25 publications

Vasculogenic and Osteogenesis-Enhancing Potential of Human Umbilical Cord Blood Endothelial Colony-Forming Cells

Vasculogenic and Osteogenesis-Enhancing Potential of Human Umbilical Cord Blood Endothelial Colony-Forming Cells

The rational use of animal models in the evaluation of novel bone regenerative therapies

Circulating osteogenic cells: Implications for injury, repair, and regeneration

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