The Immunogenicity and Immunomodulatory Function of Osteogenic Cells Differentiated from Mesenchymal Stem Cells

Liu, Hua; Kemeny, David M.; Heng, Boon Chin; Ouyang, Hong; Melendez, Alirio J.; Cao, Tong

doi:10.4049/jimmunol.176.5.2864

Cited by 191 publications

(179 citation statements)

References 51 publications

Supporting

Mentioning

165

Contrasting

Unclassified

Order By: Relevance

“…These studies have yielded variable results and no consensus conclusion has been reached. Some studies have shown that soluble factors such as TGFb [22] and PGE2 [6] mediate the immunosuppressive effect of MSCs [27][28][29]; while other researchers have argued that direct cell-cell contact is the major mechanism [30][31][32]. In the present study, we generated MSC clones from mouse bone marrow and verified that the majority of these clones possessed differentiation potential.…”

Section: Introductionmentioning

confidence: 57%

Immunosuppressive properties of cloned bone marrow mesenchymal stem cells

Xu¹,

Zhang²,

Ren³

et al. 2007

Cell Res

137

101

View full text Add to dashboard Cite

Mesenchymal stem cells (MSCs), derived from adult tissues, are multipotent progenitor cells, which hold great promise for regenerative medicine. Recent studies have shown that MSCs are immunosuppressive in vivo and in vitro in both animals and humans. However, the mechanisms that govern these immune modulatory functions of MSCs remain largely elusive. Some studies with bulk populations of MSCs indicated that soluble factors such as PGE2 and TGFb are important, while others support a role for cell-cell contact. In this study, we intended to clarify these issues by examining immunosuppressive effects of cloned MSCs. We derived MSC clones from mouse bone marrow and showed that the majority of these clones were able to differentiate into adipocytes and osteoblast-like cells. Importantly, cells from these clones exhibited strong inhibitory effects on TCR activation-induced T cell proliferation in vitro, and injection of a small number of these cells promoted the survival of allogeneic skin grafts in mice. Conditioned medium from MSC cultures showed some inhibitory effect on anti-CD3 induced lymphocyte proliferation independent of PGE2 and TGFb. In comparison, direct co-culture of MSCs with stimulated lymphocytes resulted in much stronger immunosuppressive effect. Interestingly, the suppression was bi-directional, as MSC proliferation was also reduced in the presence of lymphocytes. Taking together, our findings with cloned MSCs demonstrate that these cells exert their immunosuppressive effects through both soluble factor(s) and cell-cell contact, and that lymphocytes and MSCs are mutually inhibitory on their respective proliferation.

show abstract

Section: Introductionmentioning

confidence: 57%

Immunosuppressive properties of cloned bone marrow mesenchymal stem cells

Xu¹,

Zhang²,

Ren³

et al. 2007

Cell Res

137

101

View full text Add to dashboard Cite

show abstract

“…For cells of the endothelial differentiation lineage, it was shown that CIITA-induced MHC class II expression is able to trigger proliferation of CD4(+) T cells independent of other T-cell costimulatory ligands [29]. The importance of the inducible MHC class II expression for the immunogenicity of allogeneic adult mesenchymal stem cells (MSC) and their osteogeneic derivatives was discussed by Liu et al [30]. In that study the differentiated MSC were also not able to express MHC class II after IFNγ stimulation in vitro, but expression gradually occurred at later time points after transplantation in vivo.…”

Section: Discussionmentioning

confidence: 99%

Low immunogenicity of endothelial derivatives from rat embryonic stem cell-like cells

et al. 2009

View full text Add to dashboard Cite

Embryonic stem cells (ESC) are suggested to be immune-privileged, but they carry the risk of uncontrolled expansion and malignancy. Upon differentiation they lose their tumor-forming capacity, but they become immunogenic by the expression of a normal set of MHC molecules. This immunogenicity might trigger rejection after application in regenerative therapies. In this study MHC expression of and immune responses to endothelial derivatives of rat embryonic stem cell-like cells (RESC) under inflammatory conditions were determined in comparison to primary rat aortic endothelial cells (ECs). Cellular as well as humoral allo-recognition was analyzed in vitro. In addition, immune reactions in vivo were assessed by allo-antibody production and determination of interferon-γ (IFNγ)-secreting allo-reactive T cells. RESC derivatives expressed low but significant levels of MHC class I, and no MHC class II. In response to IFNγ MHC class I expression was enhanced, while class II transactivator induction failed completely in these cells; MHC class II expression remained consistently absent. Functionally, the RESC derivatives showed a reduced allo-stimulatory capacity, protection against humoral allo-recognition in vitro and a slightly diminished susceptibility to cytotoxic T cell lysis. Furthermore, in vivo experiments demonstrated that these cells do not trigger host immune reactions, characterized by no allo-antibody production and no induction of allo-reactive memory T cells. Our results show that endothelial derivatives of RESC have a distinctive reduced immunogenic potency even under inflammatory conditions.

show abstract

“…Although several recent studies confirmed immunological properties of bone cells [19][20][21][22]24], direct chemotactic and immunomodulatory effects of OBL and OCL have not been precisely determined. In the co-culture model we demonstrated both the ability of lymphocytes to affect bone cell differentiation and their chemotactic properties, and of bone cells to modulate the cytokine and activation profile of lymphoid cells.…”

Section: Discussionmentioning

confidence: 99%

“…A subpopulation of human OBLs expresses the major histocompatibility complex class II (MHC-II) and costimulatory molecules, thus participating in antigen presentation and T lymphocyte activation [17]. On the other hand, OBL lineage cells as well as their ancestry, bone-marrow derived mesenchymal stem cells (MSC) may exhibit immunosuppressive properties by secreting immunosuppressive cytokines and stimulating regulatory T lymphocytes [20][21][22]. It has been recently proposed that MSC may be polarized toward either the proinflammatory or the immunosuppressive subpopulation depending on the toll like receptor (TLR) triggered by an exogenous danger signals [23].…”

Section: Introductionmentioning

confidence: 99%