title: Interaction between marrow-derived human mesenchymal stem cells and peripheral blood mononuclear cells in endothelial cell differentiation.
abstract: OBJECTIVE
  In adult connective tissues, mesenchymal stem cells (MSCs) play a key role in normal tissue turnover and repair. MSCs can participate in these processes not only through proliferation and differentiation but also through paracrine/autocrine functions. These characteristics make MSCs the optimal target in the development of cell-based therapies. This study describes a novel interaction between human MSC and blood mononuclear cells (MNCs), resulting in formation of blood vessel-like structures.
  
  
  METHODS
  Human marrow-derived MSCs and peripheral blood MNCs were co-cultured in monolayer cultures as well as in bovine collagen sponge up to 20 days. No exogenously supplied growth factors were applied. Morphological changes and formations of three dimensional structures were detected by light microscopy. The process was further stu-died for the expression of different endothelial cell markers. The expression of PECAM-1 and endoglin was studied by immunohistochemistry and the expression of vascular endothelial growth factor receptors 1 and 2 using quantitative real time PCR.
  
  
  RESULTS
  In co-cultures of human MSCs and MNCs, the previously nonadherent cells attached and started to elongate and formed tube-like structures within one week. At day 10, elongated PECAM-1 and endoglin expressing cells were detected in co-cultures. At day 20, PECAM-1 and endoglin-positive vessel-like structures were observed. VEGFR1 was up-regulated in co-cultures after 10 days, and expression levels increased with time. No PECAM-1, endoglin or VEGFR1 expressing cells were discovered in MSC-cultures without MNCs at any time point.
  
  
  CONCLUSIONS
  This study demonstrates induction of endothelial differentiation in co-cultures of human MSCs and MNCs, indicating a mechanism by which local application of MSCs could induce angiogenesis in vivo.
authors: Department of Cell Biology and Anatomy, Institute of Biomedicine, University of Turku, Turku, Finland. kvjoen@utu.fi
authors: K
authors: K
authors: Joensuu
authors: I
authors: I
authors: Paatero
authors: J J
authors: JJ
authors: Alm
authors: K
authors: K
authors: Elenius
authors: H T
authors: HT
authors: Aro
authors: T J
authors: TJ
authors: Heino
authors: T A
authors: TA
authors: Hentunen
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D018920:Coculture Techniques; D000071063:Endoglin; D006801:Humans; D007150:Immunohistochemistry; D007963:Leukocytes, Mononuclear / Q000502:physiology*; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011956:Receptors, Cell Surface; D040262:Receptors, Vascular Endothelial Growth Factor