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Maxillofacial Plastic and Reconstructive Surgery

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Open Access 01-12-2017 | Research

Angiogenesis in newly regenerated bone by secretomes of human mesenchymal stem cells

Authors: Wataru Katagiri, Takamasa Kawai, Masashi Osugi, Yukiko Sugimura-Wakayama, Kohei Sakaguchi, Taku Kojima, Tadaharu Kobayashi

Published in: Maxillofacial Plastic and Reconstructive Surgery | Issue 1/2017

Abstract

Background

For an effective bone graft for reconstruction of the maxillofacial region, an adequate vascular network will be required to supply blood, osteoprogenitor cells, and growth factors. We previously reported that the secretomes of bone marrow-derived mesenchymal stem cells (MSC-CM) contain numerous growth factors such as insulin-like growth factor (IGF)-1, transforming growth factor (TGF)-β1, and vascular endothelial growth factor (VEGF), which can affect the cellular characteristics and behavior of regenerating bone cells. We hypothesized that angiogenesis is an important step for bone regeneration, and VEGF is one of the crucial factors in MSC-CM that would enhance its osteogenic potential. In the present study, we focused on VEGF in MSC-CM and evaluated the angiogenic and osteogenic potentials of MSC-CM for bone regeneration.

Methods

Cytokines in MSC-CM were measured by enzyme-linked immunosorbent assay (ELISA). Human umbilical vein endothelial cells (HUVECs) were cultured with MSC-CM or MSC-CM with anti-VEGF antibody (MSC-CM + anti-VEGF) for neutralization, and tube formation was evaluated. For the evaluation of bone and blood vessel formation with micro-computed tomography (micro-CT) and for the histological and immunohistochemical analyses, a rat calvarial bone defect model was used.

Results

The concentrations of IGF-1, VEGF, and TGF-β1 in MSC-CM were 1515.6 ± 211.8 pg/mL, 465.8 ± 108.8 pg/mL, and 339.8 ± 14.4 pg/mL, respectively. Tube formation of HUVECs, bone formation, and blood vessel formation were increased in the MSC-CM group but decreased in the MSC-CM + anti-VEGF group. Histological findings suggested that new bone formation in the entire defect was observed in the MSC-CM group although it was decreased in the MSC-CM + anti-VEGF group. Immunohistochemistry indicated that angiogenesis and migration of endogenous stem cells were much more abundant in the MSC-CM group than in the MSC-CM + anti-VEGF group.

Conclusions

VEGF is considered a crucial factor in MSC-CM, and MSC-CM is proposed to be an adequate therapeutic agent for bone regeneration with angiogenesis.

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Title: Angiogenesis in newly regenerated bone by secretomes of human mesenchymal stem cells
Authors: Wataru Katagiri
Takamasa Kawai
Masashi Osugi
Yukiko Sugimura-Wakayama
Kohei Sakaguchi
Taku Kojima
Tadaharu Kobayashi
Publication date: 01-12-2017
Publisher: Springer Berlin Heidelberg
Published in: Maxillofacial Plastic and Reconstructive Surgery / Issue 1/2017
Electronic ISSN: 2288-8586
DOI: https://doi.org/10.1186/s40902-017-0106-4

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Angiogenesis in newly regenerated bone by secretomes of human mesenchymal stem cells

Abstract

Background

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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