Dataset Information

Prevascularisation with endothelial progenitor cells improved restoration of the architectural and functional properties of newly formed bone for bone reconstruction.

ABSTRACT:

Purpose

The aim of this study was to examine whether the addition of endothelial progenitor cells (EPCs) contributes to restoring the architectural and functional properties of newly formed bone for reconstruction of bone defects.

Methods

Bone marrow-derived EPCs and mesenchymal stem cells (MSCs) were co-seeded onto demineralized bone matrix (DBM) as a prevascularized tissue-engineered bone (TEB) for the repair of segmental bone defects to evaluate the effects of prevascularization of TEB on ameliorating morphological, haemodynamic and mechanical characteristics.

Results

The restoration of the intraosseous vasculature and medullary cavity was improved markedly compared to the non-prevascularized groups. The blood supply, biomechanical strength, and bone mineral density of the prevascularized group were significantly higher than those of the non-prevascularized groups during bone reconstruction.

Conclusions

The present study indicates that EPC-dependent prevascularization contributes to bone healing with structural reconstruction and functional recovery and may improve the understanding of correlation between angiogenesis and osteogenesis.

SUBMITTER: Pang H

PROVIDER: S-EPMC3609986 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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Publications

Prevascularisation with endothelial progenitor cells improved restoration of the architectural and functional properties of newly formed bone for bone reconstruction.

Pang Hao H Wu Xue-Hui XH Fu Sheng-Long SL Luo Fei F Zhang Ze-Hua ZH Hou Tian-Yong TY Li Zhi-Qiang ZQ Chang Zheng-Qi ZQ Yu Bo B Xu Jian-Zhong JZ

International orthopaedics 20130104 4

<h4>Purpose</h4>The aim of this study was to examine whether the addition of endothelial progenitor cells (EPCs) contributes to restoring the architectural and functional properties of newly formed bone for reconstruction of bone defects.<h4>Methods</h4>Bone marrow-derived EPCs and mesenchymal stem cells (MSCs) were co-seeded onto demineralized bone matrix (DBM) as a prevascularized tissue-engineered bone (TEB) for the repair of segmental bone defects to evaluate the effects of prevascularizatio ...[more]

PMID: 23288045

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Project description:Endothelial progenitor cell (EPC)-based therapy has immense potential to promote cardiac neovascularization and attenuate ischemic injury. Functional benefits of EPCs and other adult stem cell therapies largely involve paracrine mechanisms and exosomes secreted by stem cells are emerging as pivotal paracrine entity of stem/progenitor cells. However, modest outcomes after EPC-/stem cell-based clinical trials suggest that stem cell/exosome function might be modulated by stimuli they encounter in ischemic tissues, including systemic inflammation. We hypothesized that EPCs under inflammatory stress might produce exosomes of altered and dysfunctional content, which may compromise EPC repair in ischemic heart disease. We have previously shown that EPCs obtained from interleukin-10 knockout (IL-10KO) mice (model mimicking systemic inflammation) display impaired angiogenic functions. Whether IL-10KO-EPC-derived exosomes inherit their parental dysfunctional phenotype and whether inflammatory environment alters the cargo of their secreted exosomes are not known. After cell expansion from IL-10KO and wild-type (WT) mice, we isolated exosomes and compared their functions in terms of effect on cell survival, proliferation, migration, and angiogenic capacity in vitro. WT-EPC-Exo treatment enhanced endothelial cell proliferation and tube formation, and inhibited apoptosis, whereas IL-10KO-Exo exhibited impaired or even detrimental effects, suggesting that the reparative capacity of WT-EPC-Exo is lost in exosomes derived from IL-10-KO-EPCs. Deep RNA sequencing and proteomic analyses to compare WT and IL-10KO-Exo revealed drastically altered exosome cargo. Importantly, IL-10KO-EPC-Exo were highly enriched in microRNAs and proteins that promote inflammation and apoptosis and inhibit angiogenesis. Through modulation of a specific enriched miRNA (miR-375), we partially rescued IL-10KO-EPC-Exo dysfunction. Thus, our study revealed that EPC exosomes display impaired function under inflammatory stimulus through changed exosome contents, and the dysfunction can be rescued by modulation of a specific target packed in exosomes.

Dataset Information

Prevascularisation with endothelial progenitor cells improved restoration of the architectural and functional properties of newly formed bone for bone reconstruction.

Purpose

Methods

Results

Conclusions

Publications

Prevascularisation with endothelial progenitor cells improved restoration of the architectural and functional properties of newly formed bone for bone reconstruction.

Similar Datasets

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