Bone marrow-derived mesenchymal stem cells become anti-angiogenic when chondrogenically or osteogenically differentiated: implications for bone and cartilage tissue engineering

Jennifer J. Bara, Helen E. McCarthy, William E.B. Johnson, Emma Humphrey, Sally Roberts

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Osteochondral tissue repair requires formation of vascularized bone and avascular cartilage. Mesenchymal stem cells stimulate angiogenesis both in vitro and in vivo but it is not known if these proangiogenic properties change as a result of chondrogenic or osteogenic differentiation. We investigated the angiogenic/antiangiogenic properties of equine bone marrow-derived mesenchymal stem cells (eBMSCs) before and after differentiation in vitro. Conditioned media from chondrogenic and osteogenic cell pellets and undifferentiated cells was applied to endothelial tube formation assays using Matrigel™. Additionally, the cell secretome was analysed using LC-MS/MS mass spectrometry and screened for angiogenesis and neurogenesis-related factors using protein arrays. Endothelial tube-like formation was supported by conditioned media from undifferentiated eBMSCs. Conversely, chondrogenic and osteogenic conditioned media was antiangiogenic as shown by significantly decreased length of endothelial tube-like structures and degree of branching compared to controls. Undifferentiated cells produced higher levels of angiogenesis-related proteins compared to chondrogenic and osteogenic pellets. In summary, eBMSCs produce an array of angiogenesis-related proteins and support angiogenesis in vitro via a paracrine mechanism. However, when these cells are differentiated chondrogenically or osteogenically, they produce a soluble factor(s) that inhibits angiogenesis. With respect to osteochondral tissue engineering, this may be beneficial for avascular articular cartilage formation but unfavourable for bone formation where a vascularized tissue is desired.

    Original languageEnglish
    Pages (from-to)147-159
    Number of pages13
    JournalTissue Engineering: Parts A, B and C
    Volume20
    Issue number1-2
    Early online date11 Sept 2013
    DOIs
    Publication statusPublished - 31 Dec 2013

    Bibliographical note

    This is a copy of an article published in the Tissue engineering: parts A © 2013 Mary Ann Liebert, Inc.; Tissue engineering: parts A is available online at: http://online.liebertpub.com

    Keywords

    • mesenchymal stem cells
    • bone marrow

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