Therapeutic angiogenesis induced by human umbilical cord tissue-derived mesenchymal stromal cells in a murine model of hindlimb ischemia

Ana Rita S Pereira, Teresa F Mendes, Augusto Ministro, Mariana Teixeira, Mariana Filipe, Jorge M Santos, Rita N Barcia, João Goyri O'neill, Fausto Pinto, Pedro Espadinha-Cruz, Helder J Cruz, Susana Constantino Rosa Santos

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8 Citations (Scopus)

Abstract

Background: Mesenchymal stem cells derived from human umbilical cord tissue, termed UCX (R), have the potential to promote a full range of events leading to tissue regeneration and homeostasis. The main goal of this work was to investigate UCX (R) action in experimentally induced hindlimb ischemia (HLI). Methods: UCX (R), obtained by using a proprietary technology developed by ECBio (Amadora, Portugal), were delivered via intramuscular injection to C57BL/6 females after unilateral HLI induction. Perfusion recovery, capillary and collateral density increase were evaluated by laser doppler, CD31 immunohistochemistry and diaphonisation, respectively. The activation state of endothelial cells (ECs) was analysed after EC isolation by laser capture microdissection microscopy followed by RNA extraction, cDNA synthesis and quantitative RT-PCR analysis. The UCX (R)-conditioned medium was analysed on Gallios flow cytometer. The capacity of UCX (R) in promoting tubulogenesis and EC migration was assessed by matrigel tubule formation and wound-healing assay, respectively. Results: We demonstrated that UCX (R) enhance angiogenesis in vitro via a paracrine effect. Importantly, after HLI induction, UCX (R) improve blood perfusion by stimulating angiogenesis and arteriogenesis. This is achieved through a new mechanism in which durable and simultaneous upregulation of transforming growth factor beta 2, angiopoietin 2, fibroblast growth factor 2, and hepatocyte growth factor, in endothelial cells is induced by UCX (R). Conclusions: In conclusion, our data demonstrate that UCX (R) improve the angiogenic potency of endothelial cells in the murine ischemic limb suggesting the potential of UCX (R) as a new therapeutic tool for critical limb ischemia.
Original languageEnglish
JournalSTEM CELL RESEARCH THERAPY
Volume7
DOIs
Publication statusPublished - 29 Sep 2016

Keywords

  • Cell Biology
  • Medicine, Research & Experimental

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