PMID- 21905956 OWN - NLM STAT- MEDLINE DCOM- 20120201 LR - 20181201 IS - 1477-2566 (Electronic) IS - 1465-3249 (Linking) VI - 13 IP - 10 DP - 2011 Nov TI - Immunoregulatory effects of human dental pulp-derived stem cells on T cells: comparison of transwell co-culture and mixed lymphocyte reaction systems. PG - 1205-20 LID - 10.3109/14653249.2011.605351 [doi] AB - BACKGROUND AIMS. Studies performed using human and animal models have indicated the immunoregulatory capability of mesenchymal stromal cells in several lineages. We investigated whether human dental pulp-derived stem cells (hDP-SC) have regulatory effects on phytohemagglutinin (PHA)-activated CD3(+) T cells. We aimed to define the regulatory mechanisms associated with hDP-SC that occur in mixed lymphocyte reaction (MLR) and transwell systems with PHA-CD3(+) T cells and hDP-SC at a ratio of 1:1. METHODS. Proliferation, apoptosis and pro- and anti-inflammatory cytokines of PHA-CD3(+)T cells, the expression of Regulatory T cells (Treg) markers and some regulatory factors related to hDP-SC, were studied in Both transwell and MLR are co-cultures systems. RESULTS. Anti-proliferative and apoptotic effects of hDP-SC were determined in co-culture systems. Elevated expression levels of human leukocyte antigen (HLA)-G, hepatocyte growth factor (HGF)-beta1, intracellular adhesion molecule (ICAM-1)-1, interleukin (IL)-6, IL-10, transforming growth factor (TGF)-beta1, vascular adhesion molecule (VCAM)-1 and vascular endothelial growth factor (VEGF) by hDP-SC were detected in the co-culture systems. We observed decreased expression levels of pro-inflammatory cytokines [interferon (IFN)-gamma, IL-2, IL-6 receptor (R), IL-12, Interleukin-17A (IL-17A), tumor necrosis factor (TNF)-alpha] and increased expression levels of anti-inflammatory cytokine [inducible protein (IP)-10] from PHA-CD3(+) T cells in the transwell system. Expression of Treg (CD4(+) CD25(+) Foxp3(+)) markers was significantly induced by hDP-SC in both co-culture systems. We observed apoptosis of PHA-CD3(+) T cells with 24 h using time-lapse camera photographs and active caspase labeling; it is likely that paracrine soluble factors and molecular signals secreted by hDP-SC led this apoptosis. CONCLUSIONS. We suggest that hDP-SC have potent immunoregulatory functions because of their soluble factors and cytokines via paracrine mechanisms associated with PHA-CD3(+) T cells, which could contribute to clinical therapies. FAU - Demircan, Pinar Cetinalp AU - Demircan PC AD - Center for Stem Cell and Gene Therapies Research and Practice, Institute of Health Sciences, Stem Cell Department, Kocaeli University, Turkey. FAU - Sariboyaci, Ayla Eker AU - Sariboyaci AE FAU - Unal, Zehra Seda AU - Unal ZS FAU - Gacar, Gulcin AU - Gacar G FAU - Subasi, Cansu AU - Subasi C FAU - Karaoz, Erdal AU - Karaoz E LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110912 PL - England TA - Cytotherapy JT - Cytotherapy JID - 100895309 RN - 0 (Antigens, Differentiation) RN - 0 (Cytokines) SB - IM MH - Adult MH - Adult Stem Cells/cytology/immunology/*metabolism MH - Antigens, Differentiation/metabolism MH - Apoptosis MH - Cell Proliferation MH - Cells, Cultured MH - Coculture Techniques MH - Cytokines/metabolism MH - Dental Pulp/*cytology MH - Humans MH - Immunomodulation MH - Lymphocyte Culture Test, Mixed MH - Male MH - Mesenchymal Stem Cells/cytology/immunology/*metabolism MH - Paracrine Communication MH - Stem Cell Niche MH - T-Lymphocyte Subsets/cytology/immunology/*metabolism MH - T-Lymphocytes, Regulatory/cytology/immunology/*metabolism EDAT- 2011/09/13 06:00 MHDA- 2012/02/02 06:00 CRDT- 2011/09/13 06:00 PHST- 2011/09/13 06:00 [entrez] PHST- 2011/09/13 06:00 [pubmed] PHST- 2012/02/02 06:00 [medline] AID - S1465-3249(11)70601-6 [pii] AID - 10.3109/14653249.2011.605351 [doi] PST - ppublish SO - Cytotherapy. 2011 Nov;13(10):1205-20. doi: 10.3109/14653249.2011.605351. Epub 2011 Sep 12.