Thymus-Derived Mesenchymal Stem Cells for Tissue Engineering Clinical-Grade Cardiovascular Grafts

Dominga Iacobazzi, Megan M Swim, Ambra Albertario, Massimo Caputo, Mohamed T Ghorbel

Research output: Contribution to journalArticle (Academic Journal)peer-review

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Abstract

Mesenchymal stem cells (MSCs) are attractive tools for regenerative medicine because of their multidifferentiation potential and immunomodulation capacity. In congenital heart defect surgical correction, replacement grafts lacking growth potential are commonly used. Tissue engineering promises to overcome the limitations of these grafts. In this study, we hypothesized that human thymus-derived MSCs are a suitable tool to tissue engineer a living vascular graft with good integration and patency once implanted in vivo. Human thymus-derived MSCs (hT-MSCs) were identified by the expression of MSC markers and mesenchymal differentiation potential. When cultured onto natural scaffold to produce tissue-engineered graft, hTMSCs exhibited great proliferation potential and the ability to secrete their own extracellular matrix. In addition, when implanted in vivo in a piglet model of left pulmonary grafting, the engineered graft exhibited good integration within the host tissue, indicating potential suitability for corrective cardiovascular surgery. The optimized xeno-free, good manufacturing practices-compliant culture system proved to be optimum for large-scale expansion of hT-MSCs and production of tissue-engineered cardiovascular grafts, without compromising the quality of cells. This study demonstrated the feasibility of engineering clinical-grade living autologous replacement grafts using hT-MSCs and proved the compatibility of these grafts for in vivo implantation in a left pulmonary artery position
Original languageEnglish
Pages (from-to)794-808
Number of pages15
JournalTissue Engineering, Part A
Volume24
Issue number9-10
Early online date30 Nov 2017
DOIs
Publication statusPublished - May 2018

Keywords

  • Cell Differentiation/physiology
  • Cells, Cultured
  • Heart/physiology
  • Heart Defects, Congenital/therapy
  • Humans
  • Mesenchymal Stem Cells/cytology
  • Thymus Gland/cytology
  • Tissue Engineering/methods

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  • NIHR BRC Cardiovascular

    Angelini, G. D.

    1/04/1731/03/22

    Project: Research, Parent

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