De Kock, Joery ORCID: 0000-0002-4078-4896, Meuleman, Philip ORCID: 0000-0001-6821-234X, Raicevic, Gordana, Rodrigues, Robim M., Branson, Steven, Meganathan, Kesavan, De Boe, Veerle, Sachinidis, Agapios, Leroux-Roels, Geert, Vanhaecke, Tamara ORCID: 0000-0002-6685-7299, Lagneaux, Laurence, Rogiers, Vera ORCID: 0000-0003-0635-7740 and Najar, Mehdi (2014). Human Skin-Derived Precursor Cells Are Poorly Immunogenic and Modulate the Allogeneic Immune Response. Stem Cells, 32 (8). S. 2215 - 2229. HOBOKEN: WILEY. ISSN 1549-4918

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Abstract

Human skin-derived precursors (hSKPs) are multipotent somatic stem cells that persist within the dermis throughout adulthood and harbor potential clinical applicability. In this study, we investigated their immunogenicity and immunosuppressive features, both in vitro and in vivo. As such, this study provides a solid basis for developing their future clinical applications. We found that hSKPs express HLA-ABC molecules, but not HLA-DR, rendering them poorly immunogenic. Using a coculture set-up, we could further demonstrate that hSKPs inhibit the proliferation of allogeneic activated T cells and alter their cytokine secretion profile, in a dose-dependent manner. Cotransplantation of hSKP and human peripheral blood leukocytes (PBL) into severe combined immune-deficient mice also showed a significant impairment of the graft-versus-host response 1 week post-transplantation and a drastic increase in survival time of 60%. From a mechanistic point of view, we found that hSKPs require cell contact as well as secretion of soluble inhibitory factors in order to modulate the immune response. The expression/secretion levels of these factors further increases upon inflammation or in the presence of activated T cells. As such, we believe that these features could be beneficial in a later allogeneic clinical setting, because rejection of engrafted allogeneic hSKP might be delayed or even avoided due to their own promotion of a tolerogenic microenvironment.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
De Kock, JoeryUNSPECIFIEDorcid.org/0000-0002-4078-4896UNSPECIFIED
Meuleman, PhilipUNSPECIFIEDorcid.org/0000-0001-6821-234XUNSPECIFIED
Raicevic, GordanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rodrigues, Robim M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Branson, StevenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meganathan, KesavanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
De Boe, VeerleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sachinidis, AgapiosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Leroux-Roels, GeertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vanhaecke, TamaraUNSPECIFIEDorcid.org/0000-0002-6685-7299UNSPECIFIED
Lagneaux, LaurenceUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rogiers, VeraUNSPECIFIEDorcid.org/0000-0003-0635-7740UNSPECIFIED
Najar, MehdiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-433523
DOI: 10.1002/stem.1692
Journal or Publication Title: Stem Cells
Volume: 32
Number: 8
Page Range: S. 2215 - 2229
Date: 2014
Publisher: WILEY
Place of Publication: HOBOKEN
ISSN: 1549-4918
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
HEPATOCYTE GROWTH-FACTOR; MESENCHYMAL STROMAL CELLS; MYELINATING SCHWANN-CELLS; STEM-CELLS; ADHESION MOLECULES; DIFFERENTIATION; EXPRESSION; IMMUNOSUPPRESSION; OSTEOGENESIS; ACTIVATIONMultiple languages
Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; HematologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/43352

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