Immunogenicity of Decidual Stromal Cells in an Epidermolysis Bullosa Patient and in Allogeneic Hematopoietic Stem Cell Transplantation Patients

Kaipe, Helen; Carlson, Lena-Maria; Erkers, Tom; Nava, Stefano; Molldén, Pia; Gustafsson, Britt; Qian, Hua; Li, Xiaoguang; Hashimoto, Takashi; Sadeghi, Behnam; Alheim, Mats; Ringdén, Olle

doi:10.1089/scd.2014.0568

Cited by 22 publications

(26 citation statements)

References 48 publications

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“…The data presented in Papers I and III-as well as other reports and the suggested role of MSCs as functional APCs-indicate that MSCs can induce innate 292 and adaptive immune responses 307 . In the clinical setting, DSCs have been shown to induce anti-HLA antibodies in immunocompetent individuals, whereas immune suppressed patients do not develop antibodies 350 . Also, there are only limited data on whether stromal cells avoid cytotoxic T cell activity.…”

Section: Immune Modulation In Vitromentioning

confidence: 99%

Decidual Stromal Cells Promote Regulatory T Cells and Suppress Alloreactivity in a Cell Contact-Dependent Manner

Erkers

Nava

Yosef

et al. 2013

Stem Cells and Development

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Acute graft-versus-host disease (GvHD) is a severe adverse event after stem cell transplantation. Bone marrow-derived mesenchymal stromal cells (BM-MSCs) have been used to treat GvHD, but decidual stromal cells (DSCs) isolated from term fetal membrane have advantages compared with BM-MSCs, including increased allosuppression, unlimited supply, and high expression of integrins. We introduced the use of DSCs in patients with steroid refractory aGvHD. In this study, we investigated factors of importance in the reduction of alloreactivity by DSCs. We found that DSCs need to have cell-cell contact in order to mediate suppression in mixed lymphocyte reactions (MLRs). This contact dependency is consistent with an increased frequency of CD4(+)CD25(high)FOXP3(+) regulatory T cells (Tregs) and an augmented intensity of CD25 expression in CD4(+) T cells. Blocking of the activity of indoleamine-2,3-dioxygenase (IDO), prostaglandin E2, PD-L1, and IFN-γ impaired the antiproliferative ability of the DSCs in MLRs. Neutralization of IDO also reduced the frequency of Tregs. In contrast to BM-MSCs, pretreatment of DSCs with high concentrations of IFN-γ (100 U/mL) reduced their ability to suppress alloreactivity, but stimulation of DSCs with MLR supernatants containing low levels of IFN-γ had no effect on the suppressive capacity in MLR. To conclude, DSCs differ in several aspects from MSCs and need to be close to alloreactive lymphocytes to mediate a suppressive effect and increase the frequency of Tregs. Thus, DSCs may not only use paracrine factors for systemic immunosuppression, but also more specifically target T cells locally in affected tissues.

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Section: Immune Modulation In Vitromentioning

confidence: 99%

Decidual Stromal Cells Promote Regulatory T Cells and Suppress Alloreactivity in a Cell Contact-Dependent Manner

Erkers

Nava

Yosef

et al. 2013

Stem Cells and Development

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“…However, in more recent years several groups have shown in different models that MSC do induce anti-donor immune responses from different facets of the immune system, including dendritic cells, T cells, and B-cell mediated allo-antibodies ( 4 – 7 ). Despite the fact that allogeneic MSC can be recognized by the host immune system, administration of these cells to human subjects has been shown, for the most part, to be safe in several different disease settings ( 5 , 8 – 10 ). There are a small number of studies describing several treatment emergent adverse events (TEAE) following administration of decidual stromal cells or adipose-derived stromal cells to patients, however, it appears that these are unrelated to the development of anti-donor immune responses ( 10 – 13 ).…”

Section: Introductionmentioning

confidence: 99%

“…Despite the fact that allogeneic MSC can be recognized by the host immune system, administration of these cells to human subjects has been shown, for the most part, to be safe in several different disease settings ( 5 , 8 – 10 ). There are a small number of studies describing several treatment emergent adverse events (TEAE) following administration of decidual stromal cells or adipose-derived stromal cells to patients, however, it appears that these are unrelated to the development of anti-donor immune responses ( 10 – 13 ). However, the field should remain vigilant to adverse immune responses which may have detrimental effects in the long term or if the patient receives a transplant later in life which may be rejected as a result of a pre-existing anti-donor memory response, either cellular or humoral ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

Anti-Donor Immune Responses Elicited by Allogeneic Mesenchymal Stem Cells and Their Extracellular Vesicles: Are We Still Learning?

et al. 2017

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Mesenchymal stromal cells (MSC) have been used to treat a broad range of disease indications such as acute and chronic inflammatory disorders, autoimmune diseases, and transplant rejection due to their potent immunosuppressive/anti-inflammatory properties. The breadth of their usage is due in no small part to the vast quantity of published studies showing their ability to modulate multiple immune cell types of both the innate and adaptive immune response. While patient-derived (autologous) MSC may be the safer choice in terms of avoiding unwanted immune responses, factors including donor comorbidities may preclude these cells from use. In these situations, allogeneic MSC derived from genetically unrelated individuals must be used. While allogeneic MSC were initially believed to be immune-privileged, substantial evidence now exists to prove otherwise with multiple studies documenting specific cellular and humoral immune responses against donor antigens following administration of these cells. In this article, we will review recent published studies using non-manipulated, inflammatory molecule-activated (licensed) and differentiated allogeneic MSC, as well as MSC extracellular vesicles focusing on the immune responses to these cells and whether or not such responses have an impact on allogeneic MSC-mediated safety and efficacy.

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“…All sera were kept at −80 °C for long durations and at 4 °C with 0·1% sodium azide as a preservative during experiments. Studies of the considerably large number of patients used in this study have previously been reported . All previously reported studies for smaller numbers of patients used in this study are listed in Appendix S2 (see Supporting Information).…”

Section: Methodsmentioning

confidence: 99%

Summary of results of serological tests and diagnoses for 4774 cases of various autoimmune bullous diseases consulted to Kurume University

et al. 2016

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Immunogenicity of Decidual Stromal Cells in an Epidermolysis Bullosa Patient and in Allogeneic Hematopoietic Stem Cell Transplantation Patients

Cited by 22 publications

References 48 publications

Decidual Stromal Cells Promote Regulatory T Cells and Suppress Alloreactivity in a Cell Contact-Dependent Manner

Decidual Stromal Cells Promote Regulatory T Cells and Suppress Alloreactivity in a Cell Contact-Dependent Manner

Anti-Donor Immune Responses Elicited by Allogeneic Mesenchymal Stem Cells and Their Extracellular Vesicles: Are We Still Learning?

Summary of results of serological tests and diagnoses for 4774 cases of various autoimmune bullous diseases consulted to Kurume University

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