TY - JOUR
T1 - Inflammation Alters the Secretome and Immunomodulatory Properties of Human Skin-Derived Precursor Cells
AU - De Kock, Joery
AU - Rodrigues, Robim Marcelino
AU - Branson, Steven
AU - Verhoye, Lieven
AU - Colemonts-Vroninks, Haaike
AU - Rombaut, Matthias
AU - Boeckmans, Joost
AU - Neuckermans, Jessie
AU - Lequeue, Sien
AU - Buyl, Karolien
AU - Merimi, Makram
AU - Moussa Agha, Douaa
AU - De Boe, Veerle
AU - Lagneaux, Laurence
AU - Meuleman, Philip
AU - Vanhaecke, Tamara
AU - Najar, Mehdi
N1 - Copyright:
This record is sourced from MEDLINE/PubMed, a database of the U.S. National Library of Medicine
PY - 2020/4/8
Y1 - 2020/4/8
N2 - Human skin-derived precursors (SKP) represent a group of somatic stem/precursor cells that reside in dermal skin throughout life that harbor clinical potential. SKP have a high self-renewal capacity, the ability to differentiate into multiple cell types and low immunogenicity, rendering them key candidates for allogeneic cell-based, off-the-shelf therapy. However, potential clinical application of allogeneic SKP requires that these cells retain their therapeutic properties under all circumstances and, in particular, in the presence of an inflammation state. Therefore, in this study, we investigated the impact of pro-inflammatory stimulation on the secretome and immunosuppressive properties of SKP. We demonstrated that pro-inflammatory stimulation of SKP significantly changes their expression and the secretion profile of chemo/cytokines and growth factors. Most importantly, we observed that pro-inflammatory stimulated SKP were still able to suppress the graft-versus-host response when cotransplanted with human PBMC in severe-combined immune deficient (SCID) mice, albeit to a much lesser extent than unstimulated SKP. Altogether, this study demonstrates that an inflammatory microenvironment has a significant impact on the immunological properties of SKP. These alterations need to be taken into account when developing allogeneic SKP-based therapies.
AB - Human skin-derived precursors (SKP) represent a group of somatic stem/precursor cells that reside in dermal skin throughout life that harbor clinical potential. SKP have a high self-renewal capacity, the ability to differentiate into multiple cell types and low immunogenicity, rendering them key candidates for allogeneic cell-based, off-the-shelf therapy. However, potential clinical application of allogeneic SKP requires that these cells retain their therapeutic properties under all circumstances and, in particular, in the presence of an inflammation state. Therefore, in this study, we investigated the impact of pro-inflammatory stimulation on the secretome and immunosuppressive properties of SKP. We demonstrated that pro-inflammatory stimulation of SKP significantly changes their expression and the secretion profile of chemo/cytokines and growth factors. Most importantly, we observed that pro-inflammatory stimulated SKP were still able to suppress the graft-versus-host response when cotransplanted with human PBMC in severe-combined immune deficient (SCID) mice, albeit to a much lesser extent than unstimulated SKP. Altogether, this study demonstrates that an inflammatory microenvironment has a significant impact on the immunological properties of SKP. These alterations need to be taken into account when developing allogeneic SKP-based therapies.
KW - adult stem cells
KW - cytokines
KW - immunogenicity
KW - inflammation
KW - skin stem cells
KW - stem cell-microenvironment interactions
U2 - 10.3390/cells9040914
DO - 10.3390/cells9040914
M3 - Article
C2 - 32276503
VL - 9
JO - Cells
JF - Cells
SN - 2073-4409
IS - 4
M1 - 914
ER -