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Blood Vessel Wall–Derived Endothelial Colony-Forming Cells Enhance Fracture Repair and Bone Regeneration

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Abstract

Endochondral bone formation requires new blood vessel formation, and endothelial progenitor cells (EPCs) may play a role in this process. Endothelial colony-forming cells (ECFCs), one subtype of EPCs, isolated from the microvasculature of rat lungs, exhibited cell surface antigen markers and gene products characteristic of endothelial cells and displayed high proliferative potential and an ability to form vessel-like network structures in vitro. The aim of this study was to evaluate whether ECFCs facilitate bone healing during fracture repair and stimulate bone regeneration. When type I collagen sponge containing ECFCs were surgically wrapped around the fractured femurs of rats, newly formed bone mineral at the site of fracture was 13% greater (P = 0.01) and energy to failure was 46% greater (P = 0.01) compared to sponge-wrapped fractures without ECFCs. When ECFCs in type I collagen sponge were surgically implanted into the bone defective area, more new vessels formed locally in comparison with sponge-alone controls and new bone tissues were seen. Further, co-implantation of ECFCs and hydroxyapatite/tricalcium phosphate (HA/TCP) scaffolds at the bone defective sites stimulated more new bone tissues than HA/TCP scaffold alone. These results show that cell therapy with vessel wall–derived ECFCs can induce new vessel formation, stimulate new bone formation, and facilitate bone repair and could be a useful approach to treat non-union fractures and bone defects.

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Acknowledgements

This study was supported by research funds from Purdue School of Science, Indiana University Purdue University Indianapolis (J. L.), the Riley Children’s Foundation (M. Y.), and Indiana University Collaborative Research Funds (J. L., M. Y.).

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Authors and Affiliations

  1. Department of Biology, Indiana University Purdue University Indianapolis, 723 W Michigan Street, SL306, Indianapolis, IN, 46202, USA

    Kaarthik S. Chandrasekhar, Hongkang Zhou, Wenyao Li, Brandt A. Finney & Jiliang Li

  2. Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA

    Pingyu Zeng & Mervin C. Yoder

  3. Department of Biomedical Engineering, Indiana University Purdue University Indianapolis, Indianapolis, IN, USA

    Daniel Alge

  4. Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA

    Mervin C. Yoder

Authors
  1. Kaarthik S. Chandrasekhar
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  2. Hongkang Zhou
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  4. Daniel Alge
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  5. Wenyao Li
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  8. Jiliang Li
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Correspondence to Jiliang Li.

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The authors have stated that they have no conflict of interest.

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Chandrasekhar, K.S., Zhou, H., Zeng, P. et al. Blood Vessel Wall–Derived Endothelial Colony-Forming Cells Enhance Fracture Repair and Bone Regeneration. Calcif Tissue Int 89, 347–357 (2011). https://doi.org/10.1007/s00223-011-9524-y

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  • DOI: https://doi.org/10.1007/s00223-011-9524-y

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