Placenta‐Derived Multipotent Cells Exhibit Immunosuppressive Properties That Are Enhanced in the Presence of Interferon‐γ

Abstract

Several types of nonhematopoietic stem cells, including bone marrow mesenchymal stem cells (BMMSCs) and embryonic stem cells, have been shown to have immunosuppressive properties. We show that human placenta-derived multipotent cells (PDMCs), which are isolated from a source without ethical concern and harbor multilineage differentiation potential, have strong immunosuppressive properties. PDMCs suppress both mitogen-induced and allogeneic lymphocyte proliferation in both CD4 and CD8 populations. The immunosuppression seen with PDMCs was significantly stronger than that with BMMSCs. Both PDMCs and BMMSCs express indoleamine 2,3-dioxygenase, but only PDMCs are positive for intracellular human leukocyte antigen-G (HLA). Mechanistically, suppression of lymphocyte reactivity by PDMCs is not due to cell death but to decreased cell proliferation and increased numbers of regulatory T cells. Addition of neutralizing antibodies to interleukin-10 and transforming growth factor (TGF)-␤ partially restored lymphocyte proliferation. Unlike BMMSCs, PDMCs treated with interferon-␥ for 3 days only very minimally upregulated HLA-DR. On the contrary, PD-L1, a cell surface marker that plays an inhibitory role in T-cell activation, was upregulated and TGF-␤ expression was seen. The immunosuppressive properties of PDMCs, along with their multilineage differentiation potential, ease of accessibility, and abundant cell numbers, may render these cells as good potential sources for future therapeutic applications. STEM

Preferential expansion of human umbilical cord blood-derived CD34-positive cells on major histocompatibility complex-matched amnion-derived mesenchymal stem cells

“…It is well known that MSC exert immunosuppressive effects on lymphocyte proliferation. 3,25,26 Accordingly, the lower response of the UCB lymphocytes against the MHC-mismatched Am-Ad cells might reflect this phenomenon. Figure 4A and B).…”

Dehydrated human amnion/chorion membrane regulates stem cell activity in vitro

“…Recently, multipotent MSCs have also been isolated in placental tissues, including the amnion and chorion layers of the amniotic membrane,21, 22, 23, 24 and these amniotic membrane derived stem cells have demonstrated the ability to regulate immune cells though secretion of various immunomodulatory cytokines 25, 26, 27, 28…”

Periodontal Ligament Stem Cells Regulate B Lymphocyte Function via Programmed Cell Death Protein 1

“…Adult stem cells exist in many tissues, including bone marrow, skin, adipose tissue, tendon, lung, heart, liver, placenta, and umbilical cord blood [1][2][3][4][5][6][7][8][9]. Due to their low immunogenicity and immunoregulatory function, mesenchymal stem cells (MSCs) play a key role in tissue regeneration and have been used in clinical trials in therapy for severe refractory diseases [10][11][12].…”