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Pereira AR, Mendes TF, Ministro A, et al. Therapeutic angiogenesis induced by human umbilical cord tissue-derived mesenchymal stromal cells in a murine model of hindlimb ischemia. Stem Cell Res Ther. 2016;7(1):145doi: 10.1186/s13287-016-0410-4.
Pereira, A. R., Mendes, T. F., Ministro, A., Teixeira, M., Filipe, M., Santos, J. M., Bárcia, R. N., Goyri-O'Neill, J., Pinto, F., Cruz, P. E., Cruz, H. J., & Santos, S. C. (2016). Therapeutic angiogenesis induced by human umbilical cord tissue-derived mesenchymal stromal cells in a murine model of hindlimb ischemia. Stem cell research & therapy, 7(1), 145. https://doi.org/10.1186/s13287-016-0410-4
Pereira, Ana Rita S, et al. "Therapeutic angiogenesis induced by human umbilical cord tissue-derived mesenchymal stromal cells in a murine model of hindlimb ischemia." Stem cell research & therapy vol. 7,1 (2016): 145. doi: https://doi.org/10.1186/s13287-016-0410-4
Pereira AR, Mendes TF, Ministro A, Teixeira M, Filipe M, Santos JM, Bárcia RN, Goyri-O'Neill J, Pinto F, Cruz PE, Cruz HJ, Santos SC. Therapeutic angiogenesis induced by human umbilical cord tissue-derived mesenchymal stromal cells in a murine model of hindlimb ischemia. Stem Cell Res Ther. 2016 Sep 29;7(1):145. doi: 10.1186/s13287-016-0410-4. PMID: 27680210; PMCID: PMC5041588.
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Stem Cell Res Ther. 2016 Sep 29;7(1):145. doi: 10.1186/s13287-016-0410-4.

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

Stem cell research & therapy

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

Affiliations

  1. Centro Cardiovascular da Universidade de Lisboa, Av. Prof Egas Moniz, 1649-028, Lisbon, Portugal.
  2. Centro Hospitalar Lisboa Norte, Av. Prof. Egas Moniz, 1649-035, Lisbon, Portugal.
  3. ECBio, Investigação e Desenvolvimento em Biotecnologia S.A., R. Henrique Paiva Couceiro, 27, 2700-4511, Amadora, Portugal.
  4. Nova Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, 1169-056, Lisbon, Portugal.
  5. Faculdade de Medicina da Universidade de Lisboa, Av. Prof Egas Moniz, 1649-028, Lisbon, Portugal.
  6. Centro Cardiovascular da Universidade de Lisboa, Av. Prof Egas Moniz, 1649-028, Lisbon, Portugal. [email protected].
  7. Faculdade de Medicina da Universidade de Lisboa, Av. Prof Egas Moniz, 1649-028, Lisbon, Portugal. [email protected].

PMID: 27680210 PMCID: PMC5041588 DOI: 10.1186/s13287-016-0410-4

Abstract

BACKGROUND: Mesenchymal stem cells derived from human umbilical cord tissue, termed UCX®, 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® action in experimentally induced hindlimb ischemia (HLI).

METHODS: UCX®, 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®-conditioned medium was analysed on Gallios flow cytometer. The capacity of UCX® in promoting tubulogenesis and EC migration was assessed by matrigel tubule formation and wound-healing assay, respectively.

RESULTS: We demonstrated that UCX® enhance angiogenesis in vitro via a paracrine effect. Importantly, after HLI induction, UCX® 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 β2, angiopoietin 2, fibroblast growth factor 2, and hepatocyte growth factor, in endothelial cells is induced by UCX®.

CONCLUSIONS: In conclusion, our data demonstrate that UCX® improve the angiogenic potency of endothelial cells in the murine ischemic limb suggesting the potential of UCX® as a new therapeutic tool for critical limb ischemia.

Keywords: Angiogenesis; Arteriogenesis; Critical limb ischemia; Endothelial cells; Hindlimb ischemia; Mesenchymal stem cells; UCX®

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