Temporal studies into attachment, VE-cadherin perturbation, and paracellular migration of human umbilical mesenchymal stem cells across umbilical vein endothelial monolayers

Article, Other literature type English OPEN
Ebrahim, Neven A. ; Leach, Lopa (2015)

Mesenchymal stem cells from Wharton's jelly of human umbilical cords (WJ-MSC) are a valuable alternate source of stem cells. Their role in situ and whether they can interact and cross intact endothelial monolayers requires elucidation. The aim of this study was to investigate the dynamic interactions between WJ-MSC and human umbilical vein endothelial cells (HUVEC), including attachment, transit times, extravasation pathway, and the effects of WJ-MSC on junctional vascular endothelial (VE)-cadherin. HUVEC were grown to near confluence in endothelial media and to full confluence in mixed media before the addition of PKH26-labelled WJ-MSC. Time lapse fluorescence microscopy showed stem cells undergoing membrane blebbing followed by amoeboid movement on HUVEC monolayers before rounding up and changing shape toward the spindle-shaped morphology during/after transmigration to subendothelial positions. Cells demonstrated a time lag of 60 min before paracellular extravasation, confirmed by confocal microscopy. Forty-six percent of attached cells crossed in the first 2 h. By 16 h, a majority of cells had transmigrated with >96% of cells crossing by 22 h. There were concomitant changes in endothelial junctional VE-cadherin with statistically significant increases in discontinuous staining at 2 h, return to control values at 16 h, even as from 22 h onward HUVEC displayed increased percentage of junctions with continuous staining and upregulation of protein. Our data suggests that WJ-MSC crosses the endothelial barrier through the paracellular pathway and can influence junctional organization of HUVEC with discreet perturbation of VE-cadherin preceding transmigration followed by upregulation once the adluminal side is reached. The latter may reflect a perivascular support function of WJ-MSC in the umbilical cord.
  • References (24)
    24 references, page 1 of 3

    1. Kobayashi K, T Kubota and T Aso. (1998). Study on myofibroblast differentiation in the stromal cells of Wharton's jelly: expression and localization of alpha-smooth muscle actin. Early Hum Dev 51:223-233.

    2. Fan CG, QJ Zhang and JR Zhou. (2011). Therapeutic potentials of mesenchymal stem cells derived from human umbilical cord. Stem Cell Rev 7:195-207.

    3. Sokolova IB, NN Zin'kova, EV Shvedova, PV Kruglyakov and DG Polyntsev. (2007). Distribution of mesenchymal stem cells in the area of tissue inflammation after transplantation of the cell material via different routes. Bull Exp Biol Med 143:143-146.

    4. Teo GS, JA Ankrum, R Martinelli, SE Boetto, K Simms, TE Sciuto, AM Dvorak, JM Karp and CV Carman. (2012). Mesenchymal stem cells transmigrate between and directly through tumor necrosis factor-alpha-activated endothelial cells via both leukocyte-like and novel mechanisms. Stem Cells 30:2472-2486.

    5. Schmidt A, D Ladage, C Steingen, K Brixius, T Schinkothe, FJ Klinz, RH Schwinger, U Mehlhorn and W Bloch. (2006). Mesenchymal stem cells transmigrate over the endothelial barrier. Eur J Cell Biol 85:1179-1188.

    6. Dejana E, F Orsenigo and MG Lampugnani. (2008). The role of adherens junctions and VE-cadherin in the control of vascular permeability. J Cell Sci 121:2115-2122.

    7. De Bruyn C, M Najar, G Raicevic, N Meuleman, K Pieters, B Stamatopoulos, A Delforge, D Bron and L Lagneaux. (2011). A rapid, simple, and reproducible method for the isolation of mesenchymal stromal cells from Wharton's jelly without enzymatic treatment. Stem Cells Dev 20:547- 557.

    8. Dominici M, K Le Blanc, I Mueller, I Slaper-Cortenbach, F Marini, D Krause, R Deans, A Keating, Dj Prockop and E Horwitz. (2006). Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8:315- 317.

    9. Pittenger MF, AM Mackay, SC Beck, RK Jaiswal, R Douglas, JD Mosca, MA Moorman, DW Simonetti, S Craig and DR Marshak. (1999). Multilineage potential of adult human mesenchymal stem cells. Science 284:143-147.

    10. Santos JM, RN Barcia, SI Simoes, MM Gaspar, S Calado, A Agua-Doce, SC Almeida, J Almeida, M Filipe, et al. (2013). The role of human umbilical cord tissue-derived mesenchymal stromal cells (UCX(R)) in the treatment of inflammatory arthritis. J Transl Med 11:18.

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