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Bone Marrow-Derived Mesenchymal Stem Cells Become Antiangiogenic When Chondrogenically or Osteogenically Differentiated: Implications for Bone and Cartilage Tissue Engineering
Bara, Jennifer J. Johnson, William E. B. Roberts, Sally McCarthy, Helen E. Humphrey, Emma
Bara, Jennifer J.
Johnson, William E. B.
Roberts, Sally
McCarthy, Helen E.
Humphrey, Emma
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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.
Citation
Bara, J. J., McCarthy, H. E., Humphrey, E., Johnson, W. E. B., & Roberts, S. (2014). Bone marrow-derived mesenchymal stem cells become antiangiogenic when chondrogenically or osteogenically differentiated: Implications for bone and cartilage tissue engineering. Tissue Engineering. Part A, 20(1-2), 147.
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Mary Ann Liebert
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Tissue Engineering Part A
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Article
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1937-335X