Endothelial Progenitor Cells and Mesenchymal Stem Cells Seeded onto β-TCP Granules Enhance Early Vascularization and Bone Healing in a Critical-Sized Bone Defect in Rats

Seebach, Caroline; Henrich, Dirk; Kähling, Christopher; Wilhelm, Kerstin; Tami, Andrea; Alini, Mauro; Marzi, Ingo

doi:10.1089/ten.tea.2009.0715

Cited by 173 publications

(174 citation statements)

References 53 publications

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“…Such increase in vascularization could make a direct contribution to bone formation, as evident in the increased ectopic bone formed in the EPC/MSC constructs, suggesting an interdependent relationship between vascularization and bone formation. Usami et al found a 1.6-fold higher capillary score formation on both the surface and central regions of canine-EPC/MSC scaffolds, accompanied by a 1.3-fold increase in bone area regenerated in subcutaneous implants [14], while Seebach et al demonstrated increased early vascularization in the first 4 weeks with improved bone regeneration and healing in a rat critical-sized femoral defect model after EPC/MSC implantation compared to MSC alone [13].…”

Section: Discussionmentioning

confidence: 99%

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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: 99%

“…Several groups have cocultured putative EPC with MSC or osteoblast-like cell types on the premise that this strategy will generate prevascular networks within bone tissue-engineered grafts to aid bone repair [13][14][15][16][17][18]. However, the majority of studies used ECs [19][20][21][22][23] rather than ECFC.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2012

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“…Investigators, including our group, have recently started to examine the potential of ECs (or EPCs) to treat criticalsized bone defects, either on their own [10,58,59] or in combination with MSCs [60][61][62][63]. Our preliminary study shows that there is a synergistic effect between ECs (HUVECs) and MSCs in promoting bone regeneration when implanted at the fracture gap of the large bone defects created by osteotomy at the tibial epiphysis of host recipients (orthotopic implantation) (preliminary data).…”

Section: Discussionmentioning

confidence: 96%

Oral Mucosa Harbors a High Frequency of Endothelial Cells: A Novel Postnatal Cell Source for Angiogenic Regeneration

Zhou

Rogers

Lee

et al. 2017

Stem Cells and Development

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Endothelial progenitor cells/endothelial cells (EPCs/ECs) have great potential to treat pathological conditions such as cardiac infarction, muscle ischemia, and bone fractures, but isolation of EPC/ECs from existing cell sources is challenging due to their low EC frequency. We have isolated endothelial progenitor (EP)-like cells from rat oral mucosa and characterized their yield, immunophenotype, growth, and in vivo angiogenic potential. The frequency of EP-like cells derived from oral mucosa is thousands of folds higher than EPCs derived from donor-match bone marrow samples. EP-like cells from oral mucosa were positive for EC markers CD31, VECadherin, and VEGFR2. Oral mucosa-derived EP-like cells displayed robust uptake of acetylated low-density lipoprotein and formed stable capillary networks in Matrigel. Subcutaneously implanted oral mucosa-derived EP-like cells anastomosed with host blood vessels, implicating their ability to elicit angiogenesis. Similar to endothelial colony-forming cells, EP-like cells from oral mucosa have a significantly higher proliferative rate than human umbilical vein endothelial cells. These findings identify a putative EPC source that is easily accessible in the oral cavity, potentially from discarded tissue specimens, and yet with robust yield and potency for angiogenesis in tissue and organ regeneration.

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“…This can be due both to the osteogenic and the vascular differentiation potential of MSC and EPC. In fact, cell-based therapy of MSC and EPC has been previously reported in literature in different studies [22,23,[37][38][39][40] indicating a potential to provide vascularization for constructs used in bone regeneration. Our findings, that pre-differentiated MSC/EPC showed higher bone formation by trend, confirm these cell-based strategies.…”

Section: Discussionmentioning

confidence: 98%

“…Moreover, recent investigations of our laboratory have focused on implantation of undifferentiated MSC and EPC seeded onto Tricalciumphosphate (TCP) which demonstrated enhanced bone regeneration and improved vascularization of critical size bone defects [22][23][24]. In these previous studies EPC demonstrated real angiogenic contribution.…”

Section: Introductionmentioning

confidence: 99%

Improved Bone Formation by Differentiated Mesenchymal Stem Cells and Endothelial Progenitor Cells Seeded on High Concentrated Bioglass-Polylactic Acid Composite in Calvarial Rat Bone Defect

Seebach¹

2015

SRDT

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Objective: New developed composite biomaterials with a Bioglass (BG) and Polylactic Acid (PLA) component are promising candidates for the treatment of bone defects. There is evidence that adding Mesenchymal Stem Cells (MSC) and Endothelial Progenitor Cells (EPC) significantly improve new bone formation. Thus, cell adhesion, cell viability and bone formation of these composites, when seeded with undifferentiated or differentiated progenitor cells, respectively were tested. Materials and methods:We investigated newly developed composite material consisting of Polylactic Acid (PLA), PLA and 20% Bioglass (PLA+BG 20%) or PLA and 40% Bioglass (PLA+BG 40%). These materials were seeded with either undifferentiated MSC / EPC or differentiated MSC / EPC and tested for cell adhesion and cell viability in vitro. Moreover, these composites were evaluated for bone formation in vivo. A Critical Size Defect (CSD) was made in each calvarium of 76 rats and composites were implanted. Animals were sacrificed after 14 weeks. Formation of new bone was evaluated by histomorphometry.Results: Cell adhesion and cell viability in vitro is not significantly influenced by our tested composites, but differentiated MSC/EPC seeded onto PLA+BG40 improve significantly bone formation in a calvarial rat bone defect in vivo and represent a novel cell-based therapy for bone regeneration.

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Endothelial Progenitor Cells and Mesenchymal Stem Cells Seeded onto β-TCP Granules Enhance Early Vascularization and Bone Healing in a Critical-Sized Bone Defect in Rats

Abstract: This cell approach suggests that there is a synergistic effect and that the initial stage of neovascularization by EPCs is considered to be crucial for complete bone regeneration in the late phase.

Cited by 173 publications

References 53 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

Oral Mucosa Harbors a High Frequency of Endothelial Cells: A Novel Postnatal Cell Source for Angiogenic Regeneration

Improved Bone Formation by Differentiated Mesenchymal Stem Cells and Endothelial Progenitor Cells Seeded on High Concentrated Bioglass-Polylactic Acid Composite in Calvarial Rat Bone Defect

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