Effects of mesenchymal stem cells from human induced pluripotent stem cells on differentiation, maturation, and function of dendritic cells

Abstract

BackgroundMesenchymal stem cells (MSCs) have potent immunomodulatory effects on multiple immune cells and have great potential in treating immune disorders. Induced pluripotent stem cells (iPSCs) serve as an unlimited and noninvasive source of MSCs, and iPSC-MSCs have been reported to have more advantages and exhibit immunomodulation on T lymphocytes and natural killer cells. However, the effects of iPSC-MSCs on dendritic cells (DCs) are unclear. The aim of this study is to investigate the effects of iPSC-MSCs on the differentiation, maturation, and function of DCs.MethodsHuman monocyte-derived DCs were induced and cultured in the presence or absence of iPSC-MSCs. Flow cytometry was used to analyze the phenotype and functions of DCs, and enzyme-linked immunosorbent assay (ELISA) was used to study cytokine production.ResultsIn this study, we successfully induced MSCs from different clones of human iPSCs. iPSC-MSCs exhibited a higher proliferation rate with less cell senescence than BM-MSCs. iPSC-MSCs inhibited the differentiation of human monocyte-derived DCs by both producing interleukin (IL)-10 and direct cell contact. Furthermore, iPSC-MSCs did not affect immature DCs to become mature DCs, but modulated their functional properties by increasing their phagocytic ability and inhibiting their ability to stimulate proliferation of lymphocytes. More importantly, iPSC-MSCs induced the generation of IL-10-producing regulatory DCs in the process of maturation, which was mostly mediated by a cell-cell contact mechanism.ConclusionsOur results indicate an important role for iPSC-MSCs in the modulation of DC differentiation and function, supporting the clinical application of iPSC-MSCs in DC-mediated immune diseases.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0499-0) contains supplementary material, which is available to authorized users.

Mechanisms underlying the protective effects of mesenchymal stem cell-based therapy

“…More importantly, MSCs derived from pluripotent stem cells display a higher proliferative capacity and telomerase activity. These cells have a higher proliferative capacity (more than 50 passages), and lower cell senescence than that observed in BM-MSCs [55,57,58]. We also observed no teratogenic effects of iPSC-MSCs in animal studies, implying the safety of using iPSC-MSCs [55].…”

“…MSCs can be derived from pluripotent stem cells including human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) [54,55]. Despite no direct sequencing comparisons between pluripotent stem cellderived MSCs and BM-MSCs, iPSC-MSCs indeed express typical MSC surface markers and undergo adipogenesis, osteogenesis, and chondrogenesis similar to that observed in adult BM-MSCs [55][56][57]. The functional characteristics of iPSC-MSCs have made the cells usable for tissue engineering and cellular therapeutics.…”

“…It is well documented that MSCs regulate the immune response in many diseases [69]. Accumulating evidences have demonstrated that MSCs can regulate T cell proliferation, function, balance T-helper (Th)1 and Th2 activity [69,70], upregulate the functions of regulatory T cells (Tregs) [71], suppress B cell functions [72,73], inhibit natural killer (NK) cell proliferation and function [74], and prevent dendritic cell (DC) maturation and activation [6,57,62]. MSCs can also stimulate proliferation and cytokine secretion in innate lymphoid cells (ILCs), a new family of lymphocyte-like cells, which play an important role in innate defences against pathogens [75,76].…”

Concise Review: Mesenchymal Stem Cells Derived from Human Pluripotent Cells, an Unlimited and Quality-Controllable Source for Therapeutic Applications

“…Interestingly, hiPS‐MSCs are more resistant to preactivated NK cells than BM‐MSCs . hiPS‐MSCs can also inhibit IL‐12p70 secretions and CD83 upregulation in dendritic cells and T‐cell proliferation induced by dendritic cells . It has been well‐known that BM‐MSCs possess tumor‐tropic effect.…”

Mesenchymal stromal cells shape the MDS microenvironment by inducing suppressive monocytes that dampen NK cell function

“…In addition, MSCs derived from BM of healthy donors (HDs) impair the cytolytic activity of resting NK cells through production of indoleamine 2,3-dioxygenase (IDO) and prostaglandin E2 (PGE2) (16). MSC-mediated immunosuppression may be partially explained by soluble factors secreted by MSCs, including known immunosuppressants, such as IL-10, PGE2, NO, IDO, and TGF-β (16)(17)(18)(19)(20).…”