Therapeutic options for end-stage organ failure are often limited to whole organ transplantation. The tolerance or rejection of the transplanted organ is driven by both early non-specific innate and specific adaptive responses. The use of mesenchymal stromal cells (MSCs) is considered a promising tool in regenerative medicine. Human umbilical cord (HUC) is an easily available source of MSCs, without relevant ethical issues. Moreover, Wharton's jelly-derived MSCs (WJ-MSCs), showed consistent immunomodulatory features that may be useful to promote immune tolerance in the host after transplantation. Few data are available on the phenotype of WJ-MSCs in situ. We investigated the expression of immune-related molecules, such as HLAs, IDO, CD276/B7-H3, and others, both in situ (HUC) and in in vitro-cultured WJ-MSCs. Morphological and biochemical techniques were used to define the expression of such molecules. In addition, we focused on the possible role of CD276/B7-H3 on T cells proliferation inhibition. We assessed CD276/B7-H3 expression by WJ-MSCs both in situ and alongside cell culture. WJ-MSCs were able to suppress T cell proliferation in mixed lymphocyte reaction (MLR). Moreover, we describe for the first time a specific role for CD276/B7-H3, since the immunomodulatory ability of WJ-MSCs was abolished upon anti-CD276/B7-H3 antibody addition to the MLR. These results further detail the immune regulation properties and tolerance induction exerted by human WJ-MSCs, in particular pointing to CD276/B7-H3 as one of the main involved factors. These data further suggest WJ-MSCs as potent tools to modulate local immune response in "support-type" regenerative medicine approaches.

2nd Department of Internal Medicine Faculty of Medicine Comenius University and University Hospital Bratislava Slovakia

2nd Department of Surgery Faculty of Medicine Masaryk University and St Anne's University Hospital Brno Czech Republic

Campus of Hematology F and P Cutino Villa Sofia Cervello Hospital Palermo Italy

Comenius University in Bratislava Bratislava Slovakia

Department of Biology Jessenius Faculty of Medicine in Martin Martin Slovakia

Department of Internal Medicine Brothers of Mercy Hospital Brno Czech Republic

Department of Neuroscience and Cell Biology University of Texas Medical Branch Galveston TX USA

Department of Research IRCCS ISMETT Mediterranean Institute for Transplantation and Advanced Specialized Therapies Palermo Italy

Department of Surgical Oncological and Stomatological Sciences University of Palermo Via del Vespro 129 90127 Palermo PA Italy

Department PROMISE University of Palermo Palermo Italy

Ri MED Foundation Palermo Italy

Unit of Histology and Embryology Department of Biomedicine Neurosciences and Advanced Diagnostics University of Palermo Via del Vespro 129 90127 Palermo PA Italy

Zobrazit více v PubMed

Eur J Immunol. 2009 Jul;39(7):1754-64 PubMed

Br J Cancer. 2005 Mar 14;92(5):888-90 PubMed

Stem Cells Dev. 2012 Oct 10;21(15):2900-3 PubMed

Front Immunol. 2019 Mar 06;10:309 PubMed

Curr Stem Cell Res Ther. 2013 Jan;8(1):100-13 PubMed

Blood. 2015 May 21;125(21):3335-46 PubMed

Int J Clin Exp Pathol. 2015 Nov 01;8(11):13987-95 PubMed

Basic Res Cardiol. 2009 May;104(3):307-20 PubMed

Histol Histopathol. 2013 Oct;28(10):1235-44 PubMed

Nat Rev Nephrol. 2018 Sep;14(9):558-570 PubMed

Stem Cells Dev. 2013 Jan 1;22(1):1-17 PubMed

J Tissue Eng Regen Med. 2007 Jul-Aug;1(4):296-305 PubMed

Stem Cells Dev. 2013 Oct 1;22(19):2619-29 PubMed

Int J Oncol. 2011 Feb;38(2):385-90 PubMed

Stem Cell Res Ther. 2016 Feb 11;7:29 PubMed

Transplantation. 1968 Mar;6(2):230-47 PubMed

Genomics. 2003 Sep;82(3):365-77 PubMed

Hum Vaccin Immunother. 2016;12(1):85-96 PubMed

Cancer Cell. 2004 Mar;5(3):241-51 PubMed

Stem Cells Int. 2016;2016:4709572 PubMed

Int J Organ Transplant Med. 2017;8(3):125-131 PubMed

Histopathology. 2008 Jan;52(2):203-12 PubMed

Open Biol. 2014 Oct;4(10): PubMed

Nat Immunol. 2001 Mar;2(3):269-74 PubMed

Eur J Immunol. 2012 Sep;42(9):2343-53 PubMed

Blood. 2002 May 15;99(10):3838-43 PubMed

Oncol Lett. 2015 Oct;10(4):2204-2208 PubMed

Pharmaceuticals (Basel). 2015 Apr 16;8(2):196-220 PubMed

Blood. 2007 May 15;109(10):4119-26 PubMed

Brain Behav Immun. 2015 Mar;45:180-8 PubMed

Stem Cells Transl Med. 2017 Dec;6(12):2053-2061 PubMed

Glycobiology. 2006 Nov;16(11):137R-157R PubMed

Cell Transplant. 2014;23(10):1169-85 PubMed

Cytotherapy. 2006;8(4):315-7 PubMed

Clin Exp Immunol. 2013 May;172(2):158-68 PubMed

Life Sci. 2010 Jan 30;86(5-6):145-52 PubMed

Biomedicines. 2017 Jul 01;5(3): PubMed

J Clin Invest. 2017 Jun 30;127(7):2492-2504 PubMed

Cell Immunol. 2018 Apr;326:24-32 PubMed

Front Bioeng Biotechnol. 2018 Jul 24;6:93 PubMed

Stem Cells Dev. 2010 Apr;19(4):423-38 PubMed

Immunol Rev. 2017 Mar;276(1):26-39 PubMed

Clin Cancer Res. 2016 Jul 15;22(14):3425-3431 PubMed

Cell Transplant. 2018 Jan;27(1):31-44 PubMed

Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8680-5 PubMed

Histochem Cell Biol. 2009 Feb;131(2):267-82 PubMed

Genes Immun. 2011 Apr;12(3):157-68 PubMed

Gut. 2012 Jun;61(6):894-906 PubMed

Cold Spring Harb Perspect Med. 2013 Nov 01;3(11): PubMed

Int J Mol Sci. 2013 Sep 03;14(9):17986-8001 PubMed

Facing the Challenges in the COVID-19 Pandemic Era: From Standard Treatments to the Umbilical Cord-Derived Mesenchymal Stromal Cells as a New Therapeutic Strategy

Umbilical Cord Mesenchymal Stromal Cells for Cartilage Regeneration Applications