Human mesenchymal stem cells as a stable source of VEGF‐producing cells

Vascular endothelial growth factor (VEGF) is a positive regulator and plays a crucial role in angiogenesis. We demonstrate that VEGF was highly expressed in cultures of human bone marrow‐derived mesenchymal stem cells (hMSCs) and the high expression level was maintained during prolonged culture periods (checked up to passage 10). We also confirmed that in vivo hMSCs engrafted into immunodeficient mice could survive and secreted human VEGF. These findings suggest that implantation of hMSCs is a practical means as a source of VEGF production and might be effective in neoangiogenesis. Copyright © 2008 John Wiley & Sons, Ltd.

[1]  H. Ohgushi,et al.  Tissue engineered ceramic artificial joint--ex vivo osteogenic differentiation of patient mesenchymal cells on total ankle joints for treatment of osteoarthritis. , 2005, Biomaterials.

[2]  Jacques Galipeau,et al.  Therapeutic angiogenesis using autologous bone marrow stromal cells: improved blood flow in a chronic limb ischemia model. , 2003, The Annals of thoracic surgery.

[3]  Stanley J. Wiegand,et al.  Vascular-specific growth factors and blood vessel formation , 2000, Nature.

[4]  N. Ferrara,et al.  The biology of vascular endothelial growth factor. , 1997, Endocrine reviews.

[5]  H. Ohgushi,et al.  Transplantation of Mesenchymal Stem Cells Improves Cardiac Function in a Rat Model of Dilated Cardiomyopathy , 2005, Circulation.

[6]  G. Yancopoulos,et al.  Growth factors acting via endothelial cell-specific receptor tyrosine kinases: VEGFs, angiopoietins, and ephrins in vascular development. , 1999, Genes & development.

[7]  H. Ohgushi,et al.  Cultured autologous human cells for hard tissue regeneration: preparation and characterization of mesenchymal stem cells from bone marrow. , 2004, Artificial organs.

[8]  H. Ohgushi,et al.  Intravenous administration of mesenchymal stem cells improves cardiac function in rats with acute myocardial infarction through angiogenesis and myogenesis. , 2004, American journal of physiology. Heart and circulatory physiology.

[9]  G. Kay,et al.  Mice lacking the vascular endothelial growth factor-B gene (Vegfb) have smaller hearts, dysfunctional coronary vasculature, and impaired recovery from cardiac ischemia. , 2000, Circulation research.

[10]  J. Ingwall,et al.  Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts , 2003, Nature Medicine.

[11]  A I Caplan,et al.  Stem cell technology and bioceramics: from cell to gene engineering. , 1999, Journal of biomedical materials research.

[12]  M. Pittenger,et al.  Multilineage potential of adult human mesenchymal stem cells. , 1999, Science.

[13]  M. Vingron,et al.  Gene expression profile of mouse bone marrow stromal cells determined by cDNA microarray analysis , 2003, Cell and Tissue Research.

[14]  H. Ohgushi,et al.  Hydroxyapatite ceramics as a carrier of gene-transduced bone marrow cells , 2002, Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association.

[15]  M. Karkkainen,et al.  Lymphatic endothelium: a new frontier of metastasis research , 2002, Nature Cell Biology.

[16]  P. Carmeliet.  Mechanisms of angiogenesis and arteriogenesis , 2000, Nature Medicine.

[17]  K. Lachapelle,et al.  Postnatal bone marrow stromal cells elicit a potent VEGF-dependent neoangiogenic response in vivo , 2003, Gene Therapy.

[18]  Paul D. Kessler,et al.  Human Mesenchymal Stem Cells Differentiate to a Cardiomyocyte Phenotype in the Adult Murine Heart , 2002, Circulation.