Immunogenicity and Immunomodulatory Properties of Umbilical Cord Lining Mesenchymal Stem Cells

Abstract

We here present an immunologic head-to-head comparison between human umbilical cord lining mesenchymal stem cells (clMSCs) and adult bone marrow MSCs (bmMSCs) from patients >65 years of age. clMSCs had significantly lower HLA class I expression, higher production of tolerogenic TGF-β and IL-10, and showed significantly faster proliferation. In vitro activation of allogeneic lymphocytes and xenogeneic in vivo immune activation was significantly stronger with bmMSCs, whereas immune recognition of clMSCs was significantly weaker. Thus, bmMSCs were more quickly rejected in immunocompetent mice. IFN-γ at 25 ng/ml increased both immunogenicity by upregulation of HLA class I/ HLA-DR expression and tolerogenicity by increasing intracellular HLA-G and surface HLA-E expression, augmenting TGF-β and IL-10 release, and inducing indoleamine 2,3-dioxygenase (IDO) expression. Higher concentrations of IFN-γ (>50 ng/ml) further enhanced the immunosuppressive phenotype of clMSCs, more strongly downregulating HLA-DR expression and further increasing IDO production (at 500 ng/ml). The net functional immunosuppressive efficacy of MSCs was tested in mixed lymphocyte cultures. Although both clMSCs and bmMSCs significantly reduced in vitro immune activation, clMSCs were significantly more effective than bmMSCs. The veto function of both MSC lines was enhanced in escalating IFN-γ environments. In conclusion, clMSCs show a more beneficial immunogeneic profile and stronger overall immunosuppressive potential than aged bmMSCs.

The Regenerative Medicine Laboratory: Facilitating Stem Cell Therapy for Equine Disease

“…These inherent differences appear to be further enhanced by inflammation. These transcriptome studies are compatible with in vitro tissue source comparison studies [22][23][24] that find baseline and activated MSCs from BM, cord tissue, and ASC modulate the immune response and respond to inflammatory mediators distinctly [5,25]. Although research with MSCs from different tissue sources in horses is just beginning, equine MSCs appear to be remarkably similar to other species described to date.…”

“…MSCs do not secrete immunomodulatory proteins in the absence of activation [4,5]. In vitro, activated T cells, individual or combinations of cytokines such as interferon-γ (IFNγ) or TNFα are used to activate MSCs [5].…”

“…In vitro, activated T cells, individual or combinations of cytokines such as interferon-γ (IFNγ) or TNFα are used to activate MSCs [5]. In vivo, injected MSCs will become activated by the local inflammatory milieu.…”

“…Human MSCs express the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase (IDO), known to suppress T-cell responses [4,5,26]. IDO has been implicated in the induction of tolerogenic DCs, the switch to a Th2-dominant cytokine inflammatory response and the induction of Tregs.…”

The transplantation of mesenchymal stem cells derived from unconventional sources: an innovative approach to multiple sclerosis therapy

“…Particularly, human umbilical cord blood and placenta are well-known sources of stem cells with capabilities comparable to BM-MSCs and actively involved in tissue repair mechanisms via the secretion of bioactive factors (Miao et al 2006 Baksh et al 2007). Compared to BMMSCs or AD-MSCs, fetal tissue was found to contain a sufficient number of stem cells and progenitor cells for the development and a faster rate of proliferation (Deuse et al 2011;Ishii and Eto 2014). Moreover, FA-MSCs exhibit rare chromosomal changes, a stable karyotype, late senescence, and incapacity to generate teratomas that suggest their genetic stability (Shin et al 2009).…”