Riccardo Schweizer1, Pranitha Kamat1, Dennis Schweizer2, Cyrill Dennler2, Shengye Zhang2, Jonas T Schnider2, Souzan Salemi3, Pietro Giovanoli4, Daniel Eberli3, Volker Enzmann5, Dominique Erni2, Jan A Plock6. 1. Division of Plastic and Hand Surgery, University Hospital Zurich, Zurich, Switzerland; Department of Clinical Research, University of Bern, Bern, Switzerland. 2. Department of Clinical Research, University of Bern, Bern, Switzerland. 3. Center for Clinical Research, University of Zurich, Zurich, Switzerland. 4. Division of Plastic and Hand Surgery, University Hospital Zurich, Zurich, Switzerland. 5. Department of Clinical Research, University of Bern, Bern, Switzerland; Department of Ophthalmology, University of Bern, Inselspital, Bern, Switzerland. 6. Division of Plastic and Hand Surgery, University Hospital Zurich, Zurich, Switzerland; Department of Clinical Research, University of Bern, Bern, Switzerland; Center for Clinical Research, University of Zurich, Zurich, Switzerland. Electronic address: jan.plock@usz.ch.
Abstract
BACKGROUND AIMS: Stem cells participate in vascular regeneration following critical ischemia. However, their angiogenic and remodeling properties, as well as their role in ischemia-related endothelial leukocyte activation, need to be further elucidated. Herein, we investigated the effect of bone marrow-derived mesenchymal stromal cells (BM-MSCs) in a critically ischemic murine skin flap model. METHODS: Groups received either 1 × 10(5), 5 × 10(5), or 1 × 10(6) BM-MSCs or cell-free conditioned medium (CM). Controls received sodium chloride. Intravital fluorescence microscopy was performed for morphological and quantitative assessment of micro-hemodynamic parameters over 12 days. RESULTS: Tortuosity and diameter of conduit-arterioles were pronounced in the MSC groups (P < 0.01), whereas vasodilation was shifted to the end arteriolar level in the CM group (P < 0.01). These effects were accompanied by angiopoietin-2 expression. Functional capillary density and red blood cell velocity were enhanced in all treatment groups (P < 0.01). Although a significant reduction of rolling and sticking leukocytes was observed in the MSC groups with a reduction of diameter in postcapillary venules (P < 0.01), animals receiving CM exhibited a leukocyte-endothelium interaction similar to controls. This correlated with leukocyte common antigen expression in tissue sections (P < 0.01) and p38 mitogen-activated protein kinase expression from tissue samples. Cytokine analysis from BM-MSC culture medium revealed a 50% reduction of pro-inflammatory cytokines (interleukin [IL]-1β, IL-6, IL-12, tumor necrosis factor-α, interferon-γ) and chemokines (keratinocyte chemoattractant, granulocyte colony-stimulating factor) under hypoxic conditions. DISCUSSION: We demonstrated positive effects of BM-MSCs on vascular regeneration and modulation of endothelial leukocyte adhesion in critical ischemic skin. The improvements after MSC application were dose-dependent and superior to the use of CM alone.
BACKGROUND AIMS: Stem cells participate in vascular regeneration following critical ischemia. However, their angiogenic and remodeling properties, as well as their role in ischemia-related endothelial leukocyte activation, need to be further elucidated. Herein, we investigated the effect of bone marrow-derived mesenchymal stromal cells (BM-MSCs) in a critically ischemicmurine skin flap model. METHODS: Groups received either 1 × 10(5), 5 × 10(5), or 1 × 10(6) BM-MSCs or cell-free conditioned medium (CM). Controls received sodium chloride. Intravital fluorescence microscopy was performed for morphological and quantitative assessment of micro-hemodynamic parameters over 12 days. RESULTS: Tortuosity and diameter of conduit-arterioles were pronounced in the MSC groups (P < 0.01), whereas vasodilation was shifted to the end arteriolar level in the CM group (P < 0.01). These effects were accompanied by angiopoietin-2 expression. Functional capillary density and red blood cell velocity were enhanced in all treatment groups (P < 0.01). Although a significant reduction of rolling and sticking leukocytes was observed in the MSC groups with a reduction of diameter in postcapillary venules (P < 0.01), animals receiving CM exhibited a leukocyte-endothelium interaction similar to controls. This correlated with leukocyte common antigen expression in tissue sections (P < 0.01) and p38 mitogen-activated protein kinase expression from tissue samples. Cytokine analysis from BM-MSC culture medium revealed a 50% reduction of pro-inflammatory cytokines (interleukin [IL]-1β, IL-6, IL-12, tumor necrosis factor-α, interferon-γ) and chemokines (keratinocyte chemoattractant, granulocyte colony-stimulating factor) under hypoxic conditions. DISCUSSION: We demonstrated positive effects of BM-MSCs on vascular regeneration and modulation of endothelial leukocyte adhesion in critical ischemic skin. The improvements after MSC application were dose-dependent and superior to the use of CM alone.
Authors: Riccardo Schweizer; Jonas T Schnider; Paolo M Fanzio; Wakako Tsuji; Nataliya Kostereva; Mario G Solari; Jan A Plock; Vijay S Gorantla Journal: Plast Reconstr Surg Glob Open Date: 2020-07-21
Authors: Jacques Galipeau; Mauro Krampera; John Barrett; Francesco Dazzi; Robert J Deans; Joost DeBruijn; Massimo Dominici; Willem E Fibbe; Adrian P Gee; Jeffery M Gimble; Peiman Hematti; Mickey B C Koh; Katarina LeBlanc; Ivan Martin; Ian K McNiece; Michael Mendicino; Steve Oh; Luis Ortiz; Donald G Phinney; Valerie Planat; Yufang Shi; David F Stroncek; Sowmya Viswanathan; Daniel J Weiss; Luc Sensebe Journal: Cytotherapy Date: 2015-12-23 Impact factor: 5.414
Authors: Aldo Rocca; Domenico Tafuri; Marianna Paccone; Antonio Giuliani; Anna Ginevra Immacolata Zamboli; Giuseppe Surfaro; Andrea Paccone; Rita Compagna; Maurizo Amato; Raffaele Serra; Bruno Amato Journal: Open Med (Wars) Date: 2017-10-21