Preclinical Evaluation of the Immunomodulatory Properties of Cardiac Adipose Tissue Progenitor Cells Using Umbilical Cord Blood Mesenchymal Stem Cells: A Direct Comparative Study

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Abstract
Cell-based strategies to regenerate injured myocardial tissue have emerged over the past decade, but the optimum cell type is still under scrutiny. In this context, human adult epicardial fat surrounding the heart has been characterized as a reservoir of mesenchymal-like progenitor cells (cardiac ATDPCs) with potential clinical benefits. However, additional data on the possibility that these cells could trigger a deleterious immune response following implantation are needed. Thus, in the presented study, we took advantage of the well-established low immunogenicity of umbilical cord blood-derived mesenchymal stem cells (UCBMSCs) to comparatively assess the immunomodulatory properties of cardiac ATDPCs in anin vitroallostimulatory assay using allogeneic mature monocyte-derived dendritic cells (MDDCs). Similar to UCBMSCs, increasing amounts of seeded cardiac ATDPCs suppressed the alloproliferation of T cells in a dose-dependent manner. Secretion of proinflammatory cytokines (IL6, TNFα, and IFNγ) was also specifically modulated by the different numbers of cardiac ATDPCs cocultured. In summary, we show that cardiac ATDPCs abrogate T cell alloproliferation upon stimulation with allogeneic mature MDDCs, suggesting that they could further regulate a possible harmful immune responsein vivo. Additionally, UCBMSCs can be considered as valuable tools to preclinically predict the immunogenicity of prospective regenerative cells.
Funding Information
  • Ministerio de Educacion y Ciencia (SAF2011-30067-C02-01, 122232, RD12/0019/0029, RD12/0042/0047, FIS PI14/01682, BES-2012-059761, RD12/0021/0027, 2014FI_B00649, CES07/015)
  • Fundació la Marató de TV3 (SAF2011-30067-C02-01, 122232, RD12/0019/0029, RD12/0042/0047, FIS PI14/01682, BES-2012-059761, RD12/0021/0027, 2014FI_B00649, CES07/015)
  • Red De Terapia Celular (SAF2011-30067-C02-01, 122232, RD12/0019/0029, RD12/0042/0047, FIS PI14/01682, BES-2012-059761, RD12/0021/0027, 2014FI_B00649, CES07/015)
  • Red de Investigación Cardiovascular (SAF2011-30067-C02-01, 122232, RD12/0019/0029, RD12/0042/0047, FIS PI14/01682, BES-2012-059761, RD12/0021/0027, 2014FI_B00649, CES07/015)
  • Instituto de Salud Carlos III (SAF2011-30067-C02-01, 122232, RD12/0019/0029, RD12/0042/0047, FIS PI14/01682, BES-2012-059761, RD12/0021/0027, 2014FI_B00649, CES07/015)
  • Ministerio de Economía y Competitividad (SAF2011-30067-C02-01, 122232, RD12/0019/0029, RD12/0042/0047, FIS PI14/01682, BES-2012-059761, RD12/0021/0027, 2014FI_B00649, CES07/015)
  • REDINREN (SAF2011-30067-C02-01, 122232, RD12/0019/0029, RD12/0042/0047, FIS PI14/01682, BES-2012-059761, RD12/0021/0027, 2014FI_B00649, CES07/015)
  • Agència de Gestió d’Ajuts Universitaris i de Recerca (SAF2011-30067-C02-01, 122232, RD12/0019/0029, RD12/0042/0047, FIS PI14/01682, BES-2012-059761, RD12/0021/0027, 2014FI_B00649, CES07/015)
  • Catalan Health Department (SAF2011-30067-C02-01, 122232, RD12/0019/0029, RD12/0042/0047, FIS PI14/01682, BES-2012-059761, RD12/0021/0027, 2014FI_B00649, CES07/015)

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